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Entry
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- *300415 - MYOTUBULARIN; MTM1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*300415</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</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/300415">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000171100;t=ENST00000370396" 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=4534" 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=300415" 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=ENSG00000171100;t=ENST00000370396" 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_000252,NM_001376906,NM_001376907,NM_001376908,XM_011531171,XM_011531172,XM_017029547,XM_017029548,XM_017029551,XM_047442132,XM_047442133,XM_047442134,XM_047442135,XM_047442136,XM_047442137" 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_000252" 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=300415" 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=02331&isoform_id=02331_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/MTM1" 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/2344875,2851537,4557896,21314969,119619783,119619784,119619785,119619786,158256852,221041600,221041616,221044840,768040028,768040031,1034674391,1034674393,1034674400,1778193403,1778193452,1778193466,2217392356,2217392358,2217392363,2217392365,2217392367,2217392369,2462629560,2462629562,2462629564,2462629566,2462629568,2462629570,2462629572,2462629574,2462629576,2462629578,2462629580" 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/Q13496" 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=4534" 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=ENSG00000171100;t=ENST00000370396" 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=MTM1" 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=MTM1" 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+4534" 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/MTM1" 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:4534" 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/4534" 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=chrX&hgg_gene=ENST00000370396.7&hgg_start=150562653&hgg_end=150673143&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:7448" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:7448" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/mtm1" 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=300415[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=300415[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/MTM1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000171100" 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=MTM1" 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=MTM1" 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=MTM1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/MTM1" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=MTM1&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/PA31251" 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:7448" 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/FBgn0025742.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:1099452" 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/MTM1#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:1099452" 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/4534/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/OMIA001508/" 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=4534" 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=WBGene00003475;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-051113-128" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:300415" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
|
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</span>
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</span>
|
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4534" 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=MTM1&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> 46804001<br />
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<strong>ICD10CM:</strong> G71.220<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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|
300415
|
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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>
|
|
<span class="mim-font">
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|
MYOTUBULARIN; MTM1
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</span>
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</h3>
|
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</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<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=MTM1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MTM1</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>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/X/792?start=-3&limit=10&highlight=792">Xq28</a>
|
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:150562653-150673143&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'})">X:150,562,653-150,673,143</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>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/792?start=-3&limit=10&highlight=792">
|
|
Xq28
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Myopathy, centronuclear, X-linked
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/310400"> 310400 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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<p>The MTM1 gene encodes a protein that belongs to a family of putative tyrosine phosphatases. Myotubularin is required for muscle cell differentiation. Myotubularin is also a potent phosphatidylinositol 3-phosphate (PI3P) phosphatase (<a href="#3" class="mim-tip-reference" title="Blondeau, F., Laporte, J., Bodin, S., Superti-Furga, G., Payrastre, B., Mandel, J.-L. <strong>Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway.</strong> Hum. Molec. Genet. 9: 2223-2229, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11001925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11001925</a>] [<a href="https://doi.org/10.1093/oxfordjournals.hmg.a018913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11001925">Blondeau et al., 2000</a>; <a href="#28" class="mim-tip-reference" title="Taylor, G. S., Maehama, T., Dixon, J. E. <strong>Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate.</strong> Proc. Nat. Acad. Sci. 97: 8910-8915, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10900271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10900271</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10900271[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.160255697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10900271">Taylor et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11001925+10900271" 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>According to <a href="#19" class="mim-tip-reference" title="Laporte, J., Blondeau, F., Buj-Bello, A., Tentler, D., Kretz, C., Dahl, N., Mandel, J.-L. <strong>Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human.</strong> Hum. Molec. Genet. 7: 1703-1712, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9736772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9736772</a>] [<a href="https://doi.org/10.1093/hmg/7.11.1703" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9736772">Laporte et al. (1998)</a>, 8 different genes encoding human myotubularin-related proteins had been reported: MTMR1 (<a href="/entry/300171">300171</a>) on Xq28; MTMR2 (<a href="/entry/603557">603557</a>) on 11q22; MTMR3 (<a href="/entry/603558">603558</a>) on 22q12; MTMR4 (<a href="/entry/603559">603559</a>) on chromosome 17; SBF1, also known as MTMR5 (<a href="/entry/603560">603560</a>), on 22qter; MTMR6 (<a href="/entry/603561">603561</a>) on 13q12; MTMR7 (<a href="/entry/603562">603562</a>) on 8p22; and MTMR8 (MTMR9; <a href="/entry/606260">606260</a>) on 8p23-p22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9736772" 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 consortium of 3 groups (<a href="#22" class="mim-tip-reference" title="Laporte, J., Hu, L. J., Kretz, C., Mandel, J.-L., Kioschis, P., Coy, J. F., Klauck, S. M., Poustka, A., Dahl, N. <strong>A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.</strong> Nature Genet. 13: 175-182, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640223</a>] [<a href="https://doi.org/10.1038/ng0696-175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640223">Laporte et al., 1996</a>) reported the isolation and characterization of the MTM1 gene (<a href="#22" class="mim-tip-reference" title="Laporte, J., Hu, L. J., Kretz, C., Mandel, J.-L., Kioschis, P., Coy, J. F., Klauck, S. M., Poustka, A., Dahl, N. <strong>A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.</strong> Nature Genet. 13: 175-182, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640223</a>] [<a href="https://doi.org/10.1038/ng0696-175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640223">Laporte et al., 1996</a>). They restricted the candidate region for the gene mutated in X-linked myotubular myopathy-1 (XLMTM; <a href="/entry/310400">310400</a>) to 280 kb and then used positional cloning to characterize a 3.4-kb cDNA that encodes at least 621 amino acids and a polyadenylation site. Additional clones from liver and skeletal muscle showed an alternative upstream polyadenylation site. The protein encoded by the MTM1 gene, designated myotubularin, was found to be highly conserved in yeast. The protein contains the consensus sequence for the active site of tyrosine phosphatases, a wide class of proteins involved in signal transduction. Preliminary Northern analysis showed ubiquitous expression of a 3.9-kb MTM1 transcript, while a 2.4-kb message was detected in skeletal muscle and testis. Both the high conservation in yeast and the ubiquitous expression of the MTM1 transcript contrasted strikingly with the apparent muscle specificity of the disease myotubular myopathy. <a href="#22" class="mim-tip-reference" title="Laporte, J., Hu, L. J., Kretz, C., Mandel, J.-L., Kioschis, P., Coy, J. F., Klauck, S. M., Poustka, A., Dahl, N. <strong>A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.</strong> Nature Genet. 13: 175-182, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640223</a>] [<a href="https://doi.org/10.1038/ng0696-175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640223">Laporte et al. (1996)</a> stated that at least 3 other genes, 1 located within 100 kb distal from the MTM1 gene, encode proteins with very high sequence similarities and define, together with the MTM1 gene, a new family of putative tyrosine phosphatases (PTPs) in man. <a href="#15" class="mim-tip-reference" title="Kioschis, P., Rogner, U. C., Pick, E., Klauck, S. M., Heiss, N., Siebenhaar, R., Korn, B., Coy, J. F., Laporte, J., Liechti-Gallati, S., Poustka, A. <strong>A 900-kb cosmid contig and 10 new transcripts within the candidate region for myotubular myopathy (MTM1).</strong> Genomics 33: 365-373, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8660996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8660996</a>] [<a href="https://doi.org/10.1006/geno.1996.0212" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8660996">Kioschis et al. (1996)</a> constructed a 900-kb cosmid contig including the entire MTM1 candidate region and identified 10 new transcripts within the region. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8640223+8660996" 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>By positional cloning, <a href="#22" class="mim-tip-reference" title="Laporte, J., Hu, L. J., Kretz, C., Mandel, J.-L., Kioschis, P., Coy, J. F., Klauck, S. M., Poustka, A., Dahl, N. <strong>A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.</strong> Nature Genet. 13: 175-182, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640223</a>] [<a href="https://doi.org/10.1038/ng0696-175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640223">Laporte et al. (1996)</a> mapped the MTM1 gene to Xq28. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8640223" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Kioschis, P., Wiemann, S., Heiss, N. S., Francis, F., Gotz, C., Poustka, A., Taudien, S., Platzer, M., Wiehe, T., Beckmann, G., Weber, J., Nordsiek, G., Rosenthal, A. <strong>Genomic organization of a 225-kb region in Xq28 containing the gene for X-linked myotubular myopathy (MTM1) and a related gene (MTMR1).</strong> Genomics 54: 256-266, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9828128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9828128</a>] [<a href="https://doi.org/10.1006/geno.1998.5560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9828128">Kioschis et al. (1998)</a> determined that the MTM1 and MTMR1 genes are transcribed in the same direction and are separated by 20 kb. Analysis of the genomic region containing MTM1 and MTMR1 suggested that the 2 genes are related and arose from an intrachromosomal gene duplication. The authors stated that other examples of intrachromosomal gene duplication in Xq28 include the IDS (<a href="/entry/300823">300823</a>) gene duplication and a cluster of MAGE genes (see <a href="/entry/300016">300016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9828128" 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>As part of an effort to clone the MTM1 gene, <a href="#8" class="mim-tip-reference" title="de Gouyon, B., Chatterjee, A., Monaco, A., Quaderi, N., Brown, S. D. M., Herman, G. E. <strong>Comparative mapping on the mouse X chromosome defines a myotubular myopathy equivalent region.</strong> Mammalian Genome 7: 575-579, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8678976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8678976</a>] [<a href="https://doi.org/10.1007/s003359900172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8678976">de Gouyon et al. (1996)</a> developed a YAC contig of the mouse X chromosome which included loci homologous to those within the human MTM1 critical region, a 300-kb interval between IDS (<a href="/entry/300823">300823</a>) and GABRA3 (<a href="/entry/305660">305660</a>) on Xq28. They aligned the human and murine physical maps by isolating conserved mouse genomic fragments, including CpG islands and trapped exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8678976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The SET (Suvar3-9, Enhancer of zeste, trithorax) domain was originally identified as a characteristic motif in several Drosophila proteins that contribute to epigenetic mechanisms of gene regulation. The human protooncoprotein HRX (<a href="/entry/159555">159555</a>) also contains a SET domain. <a href="#7" class="mim-tip-reference" title="Cui, X., De Vivo, I., Slany, R., Miyamoto, A., Firestein, R., Cleary, M. L. <strong>Association of SET domain and myotubularin-related proteins modulates growth control.</strong> Nature Genet. 18: 331-337, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537414</a>] [<a href="https://doi.org/10.1038/ng0498-331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537414">Cui et al. (1998)</a> determined that MTM1 and SBF1 (<a href="/entry/603560">603560</a>) interacted with HRX in vitro and in vivo. This interaction was abrogated in an oncogenic form of HRX lacking the SET domain. Like HRX, both SBF1 and MTM1 localized to the nucleus of mammalian cells. The authors found that MTM1 and SBF1 have a conserved SET interaction domain (SID) that displays a paired amphipathic helix secondary structure. In contrast with MTM1, SBF1 lacked dual-specificity phosphatase activity in vitro, suggesting that SBF1 acts as a protective factor that prevents substrate dephosphorylation. Ectopic expression of SBF1 impaired the in vitro differentiation of myoblast cells, implying that interactions of SET-domain proteins with catalytically active members of the myotubularin family are essential for execution of the myogenic program. The authors stated that these results are consistent with the adverse effects of inherited MTM1 loss-of-function mutations on muscle maturation in X-linked myotubular myopathy (XLMTM). They concluded that myotubularin proteins link SET domain-containing components of the epigenetic regulatory machinery with signaling pathways involved in differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537414" 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="#28" class="mim-tip-reference" title="Taylor, G. S., Maehama, T., Dixon, J. E. <strong>Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate.</strong> Proc. Nat. Acad. Sci. 97: 8910-8915, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10900271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10900271</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10900271[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.160255697" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10900271">Taylor et al. (2000)</a> reported that myotubularin, a protein-tyrosine phosphatase required for muscle cell differentiation, is a potent phosphatidylinositol 3-phosphate (PI3P) phosphatase. They found that mutations in the MTM1 gene that cause human myotubular myopathy dramatically reduced the ability of the phosphatase to dephosphorylate PI3P. The findings provided evidence that myotubularin exerts its effects during myogenesis by regulating the cellular levels of the inositol lipid PI3P. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10900271" 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="#3" class="mim-tip-reference" title="Blondeau, F., Laporte, J., Bodin, S., Superti-Furga, G., Payrastre, B., Mandel, J.-L. <strong>Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway.</strong> Hum. Molec. Genet. 9: 2223-2229, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11001925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11001925</a>] [<a href="https://doi.org/10.1093/oxfordjournals.hmg.a018913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11001925">Blondeau et al. (2000)</a> investigated the activity and substrate specificity of MTM1. Expression of active human myotubularin inhibited growth of S. pombe and induced a vacuolar phenotype similar to that of mutants of the vacuolar protein sorting (VPS) pathway and notably of mutants of VPS34, a phosphatidylinositol 3-kinase (PI3K; see <a href="/entry/602838">602838</a>). In S. pombe cells deleted for the endogenous MTM homologous gene, expression of human myotubularin decreased the level of phosphatidylinositol 3-phosphate (PI3P). A substrate trap mutant relocalized to plasma membrane projections (spikes) in HeLa cells and was inactive in the S. pombe assay. This mutant, but not the wildtype or a phosphatase site mutant, was able to immunoprecipitate a VPS34 kinase activity. Wildtype myotubularin was also able to directly dephosphorylate PI3P and PI4P in vitro. The authors hypothesized that myotubularin may decrease PI3P levels by downregulating PI3K activity and by directly degrading PI3P. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11001925" 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="Laporte, J., Blondeau, F., Buj-Bello, A., Mandel, J.-L. <strong>The myotubularin family: from genetic disease to phosphoinositide metabolism.</strong> Trends Genet. 17: 221-228, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11275328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11275328</a>] [<a href="https://doi.org/10.1016/s0168-9525(01)02245-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11275328">Laporte et al. (2001)</a> provided an extensive review of the myotubularin-related genes. These genes define a large family of eukaryotic proteins, most of which were initially characterized by the presence of a 10-amino acid consensus sequence related to the active sites of tyrosine phosphatases, dual-specificity protein phosphatases, and the lipid phosphatase PTEN (<a href="/entry/601728">601728</a>). MTM1 is the founding member of the family. A close homolog, MTMR2 (<a href="/entry/603557">603557</a>), is mutated in a recessive form of Charcot-Marie-Tooth neuropathy (<a href="/entry/601382">601382</a>). <a href="#18" class="mim-tip-reference" title="Laporte, J., Blondeau, F., Buj-Bello, A., Mandel, J.-L. <strong>The myotubularin family: from genetic disease to phosphoinositide metabolism.</strong> Trends Genet. 17: 221-228, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11275328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11275328</a>] [<a href="https://doi.org/10.1016/s0168-9525(01)02245-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11275328">Laporte et al. (2001)</a> pointed out that although myotubularin was thought to be a dual-specificity protein phosphatase, studies indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and possibly involved in the regulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11275328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Nandurkar, H. H., Layton, M., Laporte, J., Selan, C., Corcoran, L., Caldwell, K. K., Mochizuki, Y., Majerus, P. W., Mitchell, C. A. <strong>Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter (sic) protein, 3-PAP.</strong> Proc. Nat. Acad. Sci. 100: 8660-8665, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12847286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12847286</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12847286[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1033097100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12847286">Nandurkar et al. (2003)</a> identified myotubularin as the catalytically active 3-phosphatase subunit interacting with 3PAP (<a href="/entry/606501">606501</a>). Recombinant myotubularin localized to the plasma membrane, causing extensive filopodia formation. However, coexpression of 3PAP with myotubularin led to attenuation of the plasma membrane phenotype, associated with myotubularin relocalization to the cytosol. Collectively these studies indicated that 3PAP functions as an 'adaptor' for myotubularin, regulating myotubularin intracellular location and thereby altering the phenotype resulting from myotubularin overexpression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12847286" 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="#14" class="mim-tip-reference" title="Ketel, K., Krauss, M., Nicot, A.-S., Puchkov, D., Wieffer, M., Muller, R., Subramanian, D., Schultz, C., Laporte, J., Haucke, V. <strong>A phosphoinositide conversion mechanism for exit from endosomes.</strong> Nature 529: 408-412, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26760201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26760201</a>] [<a href="https://doi.org/10.1038/nature16516" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26760201">Ketel et al. (2016)</a> reported that surface delivery of endosomal cargo requires hydrolysis of PI(3)P by the phosphatidylinositol 3-phosphatase MTM1, an enzyme whose loss of function leads to X-linked centronuclear myopathy (also called myotubular myopathy) in humans. Removal of endosomal PI(3)P by MTM1 is accompanied by phosphatidylinositol 4-kinase-2-alpha (PI4K2-alpha)-dependent generation of PI(4)P and recruitment of the exocyst tethering complex to enable membrane fusion. <a href="#14" class="mim-tip-reference" title="Ketel, K., Krauss, M., Nicot, A.-S., Puchkov, D., Wieffer, M., Muller, R., Subramanian, D., Schultz, C., Laporte, J., Haucke, V. <strong>A phosphoinositide conversion mechanism for exit from endosomes.</strong> Nature 529: 408-412, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26760201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26760201</a>] [<a href="https://doi.org/10.1038/nature16516" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26760201">Ketel et al. (2016)</a> concluded that their data established a mechanism for phosphoinositide conversion from PI(3)P to PI(4)P at endosomes en route to the plasma membrane and suggested that defective phosphoinositide conversion at endosomes underlies X-linked centronuclear myopathy caused by mutation of MTM1 in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26760201" 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 male with XLMTM, <a href="#22" class="mim-tip-reference" title="Laporte, J., Hu, L. J., Kretz, C., Mandel, J.-L., Kioschis, P., Coy, J. F., Klauck, S. M., Poustka, A., Dahl, N. <strong>A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.</strong> Nature Genet. 13: 175-182, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640223</a>] [<a href="https://doi.org/10.1038/ng0696-175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640223">Laporte et al. (1996)</a> demonstrated an A-to-G transition at nucleotide 620 predicting a substitution of serine for asparagine-207 in the MTM1 gene (<a href="#0001">300415.0001</a>). This was 1 of 4 missense mutations that, together with 3 frameshift mutations, were found in 7 of 60 MTM1 patients studied. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8640223" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By direct genomic sequencing of 92% of the known coding sequence of the myotubularin gene, <a href="#9" class="mim-tip-reference" title="de Gouyon, B. M., Zhao, W., Laporte, J., Mandel, J.-L., Metzenberg, A., Herman, G. E. <strong>Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy.</strong> Hum. Molec. Genet. 6: 1499-1504, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285787</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285787">de Gouyon et al. (1997)</a> identified mutations in 26 of 41 unrelated male patients with muscle biopsy-proven myotubular myopathy. Point mutations were found in 18 patients, including an A-to-G transition found in 4 patients, which altered a splice acceptor site in exon 12 and led to a 3-amino acid insertion. Six patients had small deletions involving less than 6 bp, while 2 larger deletions encompassed 2 and 6 exons, respectively. All 5 patients with a mild phenotype had missense mutations (e.g., <a href="#0003">300415.0003</a>). While 50% of the mutations were found in exons 4 and 12, and 3 distinct mutations were found in more than 1 patient, no single mutation accounted for more than 10% of the cases. Low frequency of large deletions and the varied mutations identified suggested to <a href="#9" class="mim-tip-reference" title="de Gouyon, B. M., Zhao, W., Laporte, J., Mandel, J.-L., Metzenberg, A., Herman, G. E. <strong>Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy.</strong> Hum. Molec. Genet. 6: 1499-1504, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285787</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285787">de Gouyon et al. (1997)</a> that direct mutation screening for molecular diagnosis may require gene sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9285787" 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>Simultaneously, a consortium of 3 groups of investigators (<a href="#21" class="mim-tip-reference" title="Laporte, J., Guiraud-Chaumeil, C., Vincent, M.-C., Mandel, J.-L., Tanner, S. M., Liechti-Gallati, S., Wallgren-Pettersson, C., Dahl, N., Kress, W., Bolhuis, P. A., Fardeau, M., Samson, F., Bertini, E., members of the ENMC International Consortium on Myotubular Myopathy. <strong>Mutations in the MTM1 gene implicated in X-linked myotubular myopathy.</strong> Hum. Molec. Genet. 6: 1505-1511, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9305655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9305655</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9305655">Laporte et al., 1997</a>) reported the identification of MTM1 mutations in 55 of 85 unrelated patients screened by SSCP for all the coding sequence. Large deletions were observed in only 3 patients. Five point mutations were found in multiple unrelated patients, accounting for 27% of the observed mutations. More than half of the mutations were expected to inactivate the putative enzymatic activity of myotubularin, either by truncation or by missense mutations affecting the predicted protein tyrosine phosphatase domain. <a href="#21" class="mim-tip-reference" title="Laporte, J., Guiraud-Chaumeil, C., Vincent, M.-C., Mandel, J.-L., Tanner, S. M., Liechti-Gallati, S., Wallgren-Pettersson, C., Dahl, N., Kress, W., Bolhuis, P. A., Fardeau, M., Samson, F., Bertini, E., members of the ENMC International Consortium on Myotubular Myopathy. <strong>Mutations in the MTM1 gene implicated in X-linked myotubular myopathy.</strong> Hum. Molec. Genet. 6: 1505-1511, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9305655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9305655</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9305655">Laporte et al. (1997)</a> suggested that there are likely to be other functional domains of the protein since additional missense mutations were clustered in 2 regions of the protein where the affected amino acids are conserved in yeast and C. elegans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9305655" 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 3 families previously investigated by linkage analysis, <a href="#27" class="mim-tip-reference" title="Tanner, S. M., Laporte, J., Guiraud-Chaumeil, C., Liechti-Gallati, S. <strong>Confirmation of prenatal diagnosis results of X-linked recessive myotubular myopathy by mutational screening, and description of three new mutations in the MTM1 gene.</strong> Hum. Mutat. 11: 62-68, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450905</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:1<62::AID-HUMU10>3.0.CO;2-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9450905">Tanner et al. (1998)</a> identified 3 new mutations in the MTM1 gene as the cause of X-linked recessive myotubular myopathy: an acceptor splice site mutation (<a href="#0004">300415.0004</a>), a frameshift mutation (<a href="#0005">300415.0005</a>), and an intronic mutation involving a cryptic splice site (<a href="#0006">300415.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Buj-Bello, A., Biancalana, V., Moutou, C., Laporte, J., Mandel, J.-L. <strong>Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy.</strong> Hum. Mutat. 14: 320-325, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502779</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<320::AID-HUMU7>3.0.CO;2-O" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10502779">Buj-Bello et al. (1999)</a> reported the identification of 21 mutations (14 novel) in XLMTM patients. Seventeen mutations were associated with a severe phenotype. The other 4 mutations (3 missense and 1 single-amino acid deletion) were found in patients with a much milder phenotype; although all of them had severe hypotonia at birth, the hypotonia improved with age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Laporte, J., Guiraud-Chaumeil, C., Tanner, S. M., Blondeau, F., Hu, L.-J., Vicaire, S., Liechti-Gallati, S., Mandel, J.-L. <strong>Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy.</strong> Europ. J. Hum. Genet. 6: 325-330, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9781038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9781038</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9781038">Laporte et al. (1998)</a> determined intronic flanking sequences for all 15 exons of the MTM1 gene to facilitate the detection of mutations in patients and genetic counseling. They characterized a new polymorphic marker in the immediate vicinity of the gene that might prove useful for linkage analysis. <a href="#17" class="mim-tip-reference" title="Laporte, J., Biancalana, V., Tanner, S. M., Kress, W., Schneider, V., Wallgren-Pettersson, C., Herger, F., Buj-Bello, A., Blondeau, F., Liechti-Gallati, S., Mandel, J.-L. <strong>MTM1 mutations in X-linked myotubular myopathy.</strong> Hum. Mutat. 15: 393-409, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790201</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<393::AID-HUMU1>3.0.CO;2-R" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10790201">Laporte et al. (2000)</a> reported 29 mutations in cases of myotubular myopathy, including 16 novel mutations. They stated that 198 mutations had been identified in unrelated families, accounting for 133 different disease-associated mutations widely distributed throughout the gene. Most of the point mutations were truncating, but 26% (35 of 133) were missense mutations affecting residues conserved in the Drosophila ortholog and in the homologous MTMR1 gene. Three recurrent mutations affected 17% of the patients, and a total of 21 mutations were found in several independent families. The frequency of female carriers appeared higher than expected; only 17% were de novo mutations. Whereas most truncating mutations caused a severe and early lethal phenotype, some missense mutations were associated with milder forms and prolonged survival, up to 54 years in the first reported family (<a href="#30" class="mim-tip-reference" title="Van Wijngaarden, G. K., Fleury, P., Bethlem, J., Meijer, A. E. F. H. <strong>Familial 'myotubular' myopathy.</strong> Neurology 19: 901-908, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5816884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5816884</a>] [<a href="https://doi.org/10.1212/wnl.19.9.901" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5816884">Van Wijngaarden et al., 1969</a>; <a href="#1" class="mim-tip-reference" title="Barth, P. G., Dubowitz, V. <strong>X-linked myotubular myopathy--a long-term follow-up study.</strong> Europ. J. Paediat. Neurol. 2: 49-56, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10726846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10726846</a>] [<a href="https://doi.org/10.1016/1090-3798(98)01004-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10726846">Barth and Dubowitz, 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10726846+9781038+10790201+5816884" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Herman, G. E., Kopacz, K., Zhao, W., Mills, P. L., Metzenberg, A., Das, S. <strong>Characterization of mutations in fifty North American patients with X-linked myotubular myopathy.</strong> Hum. Mutat. 19: 114-121, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11793470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11793470</a>] [<a href="https://doi.org/10.1002/humu.10033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11793470">Herman et al. (2002)</a> stated that 133 different mutations had been identified in the MTM1 gene worldwide. They reported mutations detected in 50 additional U.S. families with biopsy-proven MTM1. Eighteen novel mutations were identified in 41 patients who had not previously been described. Eighty-eight percent of the mothers of sporadic cases studied were identified as carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11793470" 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="Tsai, T.-C., Horinouchi, H., Noguchi, S., Minami, N., Murayama, K., Hayashi, Y. K., Nonaka, I., Nishino, I. <strong>Characterization of MTM1 mutations in 31 Japanese families with myotubular myopathy, including a patient carrying 240 kb deletion in Xq28 without male hypogenitalism.</strong> Neuromusc. Disord. 15: 245-252, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15725586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15725586</a>] [<a href="https://doi.org/10.1016/j.nmd.2004.12.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15725586">Tsai et al. (2005)</a> reported 31 Japanese patients with myotubular myopathy caused by mutation in the MTM1 gene, and identified 14 novel mutations. Truncating mutations and gene-abolishing large deletions accounted for 52% of the mutations. A splice site mutation (<a href="#0006">300415.0006</a>) was identified in 3 unrelated patients, suggesting it is a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15725586" 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>To understand the pathophysiologic mechanism of XLMTM, <a href="#5" class="mim-tip-reference" title="Buj-Bello, A., Laugel, V., Messaddeq, N., Zahreddine, H., Laporte, J., Pellissier, J.-F., Mandel, J.-L. <strong>The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice.</strong> Proc. Nat. Acad. Sci. 99: 15060-15065, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12391329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12391329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12391329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.212498399" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12391329">Buj-Bello et al. (2002)</a> generated mice lacking myotubularin by homologous recombination. These mice were viable, but their life span was severely reduced. They developed a generalized and progressive myopathy starting at approximately 4 weeks of age, with amyotrophy and accumulation of central nuclei in skeletal muscle fibers leading to death at 6 to 14 weeks of age. <a href="#5" class="mim-tip-reference" title="Buj-Bello, A., Laugel, V., Messaddeq, N., Zahreddine, H., Laporte, J., Pellissier, J.-F., Mandel, J.-L. <strong>The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice.</strong> Proc. Nat. Acad. Sci. 99: 15060-15065, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12391329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12391329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12391329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.212498399" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12391329">Buj-Bello et al. (2002)</a> showed that muscle differentiation in knockout mice occurred normally, contrary to expectations. They provided evidence that fibers with centralized myonuclei originate mainly from a structural maintenance defect affecting myotubularin-deficient muscle rather than a regenerative process. In addition, they demonstrated through a conditional gene-targeting approach that skeletal muscle is the primary target of murine XLMTM pathology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12391329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Dowling, J. J., Vreede, A. P., Low, S. E., Gibbs, E. M., Kuwada, J. Y., Bonnemann, C. G., Feldman, E. L. <strong>Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy.</strong> PLoS Genet. 5: e1000372, 2009. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19197364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19197364</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19197364[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.1000372" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19197364">Dowling et al. (2009)</a> observed that zebrafish with reduced levels of myotubularin had significantly impaired motor function and obvious histopathologic muscle changes, including abnormally shaped and positioned nuclei and myofiber hypotrophy, as observed in the human disease. Loss of myotubularin caused increased PI3P levels in muscle in vivo. Morpholino knockdown of Mtm1 in zebrafish muscle resulted in abnormalities in the T-tubule and sarcoplasmic reticulum network, similar to T-tubule disorganization observed in patients with myotubular myopathy. Expression of the homologous myotubularin-related proteins Mtmr1 and Mtmr2 could functionally compensate for the loss of myotubularin in zebrafish. <a href="#10" class="mim-tip-reference" title="Dowling, J. J., Vreede, A. P., Low, S. E., Gibbs, E. M., Kuwada, J. Y., Bonnemann, C. G., Feldman, E. L. <strong>Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy.</strong> PLoS Genet. 5: e1000372, 2009. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19197364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19197364</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19197364[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.1000372" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19197364">Dowling et al. (2009)</a> suggested that XLMTM may be linked mechanistically by tubuloreticular abnormalities and defective excitation-contraction coupling to myopathies caused by mutations in the RYR1 gene (<a href="/entry/180901">180901</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19197364" 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="Fetalvero, K. M., Yu, Y., Goetschkes, M., Liang, G., Valdez, R. A., Gould, T., Triantafellow, E., Bergling, S., Loureiro, J., Eash, J., Lin, V., Porter, J. A., Finan, P. M., Walsh, K., Yang, Y., Mao, X., Murphy, L. O. <strong>Defective autophagy and mTORC1 signaling in myotubularin null mice.</strong> Molec. Cell. Biol. 33: 98-110, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23109424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23109424</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23109424[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.01075-12" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23109424">Fetalvero et al. (2013)</a> found that Mtm1 -/- skeletal muscle showed increased content of PI3P, ubiquitinated proteins, and lipidated proteins normally degraded via autophagy. Mtm1 -/- skeletal muscle also showed accumulation of defective mitochondria with decreased COX enzyme activity and elevated activity of mTORC1 (see <a href="/entry/601231">601231</a>), a major nutrient sensor and autophagy inhibitor. No change in mTORC1, mitochondria, or content of nondegraded proteins was observed in liver, heart, or brain of Mtm1 -/- mice. Overnight fasting activated mTORC1-dependent inhibition of autophagy in wildtype, but not Mtm1 -/-, skeletal muscle. Inhibition of hyperactivated mTORC1 normalized autophagy and rescued muscle mass in Mtm1 -/- mice. <a href="#11" class="mim-tip-reference" title="Fetalvero, K. M., Yu, Y., Goetschkes, M., Liang, G., Valdez, R. A., Gould, T., Triantafellow, E., Bergling, S., Loureiro, J., Eash, J., Lin, V., Porter, J. A., Finan, P. M., Walsh, K., Yang, Y., Mao, X., Murphy, L. O. <strong>Defective autophagy and mTORC1 signaling in myotubularin null mice.</strong> Molec. Cell. Biol. 33: 98-110, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23109424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23109424</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23109424[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.01075-12" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23109424">Fetalvero et al. (2013)</a> concluded that MTM1 is involved in regulation of mTORC1 and autophagy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23109424" 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="Cowling, B. S., Chevremont, T., Prokic, I., Kretz, C., Ferry, A., Coirault, C., Koutsopoulos, O., Laugel, V., Romero, N. B., Laporte, J. <strong>Reducing dynamin 2 expression rescues X-linked centronuclear myopathy.</strong> J. Clin. Invest. 124: 1350-1363, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24569376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24569376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24569376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI71206" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24569376">Cowling et al. (2014)</a> found a 1.5-fold increase in DNM2 (<a href="/entry/602378">602378</a>) expression in muscle biopsies isolated from human patients with CNMX (XLMTM) and in heterozygous Mtm1 -/y mice compared to controls. Crossing Mtm1 -/y with Dnm2 +/- mice resulted in increased survival and greatly improved muscle strength, suggesting that reduced expression of the Dnm2 gene can rescue the early lethality observed in Mtm1 -/y mice. Skeletal muscle from the double-mutant mice showed decreased or even rescued atrophy compared to Mtm1 -/y mice, and histologic abnormalities such as fiber atrophy and nuclei mispositioning were absent or reduced in the double-mutant mice. Ultrastructural analysis showed improvement of sarcomere organization and triad structures. In addition, muscle-specific reduction of Dnm2, particularly in the diaphragm, was sufficient to rescue the lethal phenotype even after birth and the onset of symptoms. The findings indicated that MTM1 and DNM2 regulate muscle organization and force through a common pathway, and suggested that MTM1 may act as a negative regulator of DNM2. <a href="#6" class="mim-tip-reference" title="Cowling, B. S., Chevremont, T., Prokic, I., Kretz, C., Ferry, A., Coirault, C., Koutsopoulos, O., Laugel, V., Romero, N. B., Laporte, J. <strong>Reducing dynamin 2 expression rescues X-linked centronuclear myopathy.</strong> J. Clin. Invest. 124: 1350-1363, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24569376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24569376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24569376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI71206" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24569376">Cowling et al. (2014)</a> concluded that reduction of DNM2 protein levels may provide a therapeutic approach for patients with CNMX. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24569376" 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 male with X-linked myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>), <a href="#22" class="mim-tip-reference" title="Laporte, J., Hu, L. J., Kretz, C., Mandel, J.-L., Kioschis, P., Coy, J. F., Klauck, S. M., Poustka, A., Dahl, N. <strong>A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.</strong> Nature Genet. 13: 175-182, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640223</a>] [<a href="https://doi.org/10.1038/ng0696-175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640223">Laporte et al. (1996)</a> demonstrated an A-to-G transition of nucleotide 620 predicting a substitution of serine for asparagine-207 in the MTM1 gene. This was 1 of 4 missense mutations that, together with 3 frameshift mutations, were found in 7 of 60 MTM1 patients studied. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8640223" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011803" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011803" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011803</a>
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<p>In an affected individual thought to have a form of X-linked myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>) distinct from the Xq28 form (<a href="#24" class="mim-tip-reference" title="Samson, F., Mesnard, L., Heimburger, M., Hanauer, A., Chevallay, M., Mercadier, J. J., Pelissier, J. F., Feingold, N., Junien, C., Mandel, J.-L., Fardeau, M. <strong>Genetic linkage heterogeneity in myotubular myopathy.</strong> Am. J. Hum. Genet. 57: 120-126, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7611280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7611280</a>]" pmid="7611280">Samson et al., 1995</a>), <a href="#12" class="mim-tip-reference" title="Guiraud-Chaumeil, C., Vincent, M. C., Laporte, J., Fardeau, M., Samson, F., Mandel, J.-L. <strong>A mutation in the MTM1 gene invalidates a previous suggestion of nonallelic heterogeneity in X-linked myotubular myopathy. (Letter)</strong> Am. J. Hum. Genet. 60: 1542-1544, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199578</a>] [<a href="https://doi.org/10.1016/S0002-9297(07)64249-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199578">Guiraud-Chaumeil et al. (1997)</a> found a single basepair change, 1244A-G, resulting in a change of tyrosine-415 to cysteine in the predicted protein (called myotubularin by them). This tyrosine coded in exon c (<a href="#22" class="mim-tip-reference" title="Laporte, J., Hu, L. J., Kretz, C., Mandel, J.-L., Kioschis, P., Coy, J. F., Klauck, S. M., Poustka, A., Dahl, N. <strong>A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.</strong> Nature Genet. 13: 175-182, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640223</a>] [<a href="https://doi.org/10.1038/ng0696-175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640223">Laporte et al., 1996</a>) is close to the putative tyrosine phosphatase active site (positions 389 to 402) and is conserved in the homologs of myotubularin in both yeast and C. elegans. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8640223+7611280+9199578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630304 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630304;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=rs132630304" 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=rs132630304" 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=RCV000011804 OR RCV003441713 OR RCV004732460" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011804, RCV003441713, RCV004732460" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011804...</a>
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<p>In 3 patients with X-linked myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>) studied by <a href="#9" class="mim-tip-reference" title="de Gouyon, B. M., Zhao, W., Laporte, J., Mandel, J.-L., Metzenberg, A., Herman, G. E. <strong>Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy.</strong> Hum. Molec. Genet. 6: 1499-1504, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285787</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285787">de Gouyon et al. (1997)</a> and in 1 patient studied by <a href="#21" class="mim-tip-reference" title="Laporte, J., Guiraud-Chaumeil, C., Vincent, M.-C., Mandel, J.-L., Tanner, S. M., Liechti-Gallati, S., Wallgren-Pettersson, C., Dahl, N., Kress, W., Bolhuis, P. A., Fardeau, M., Samson, F., Bertini, E., members of the ENMC International Consortium on Myotubular Myopathy. <strong>Mutations in the MTM1 gene implicated in X-linked myotubular myopathy.</strong> Hum. Molec. Genet. 6: 1505-1511, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9305655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9305655</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9305655">Laporte et al. (1997)</a>, a C-to-T transition of nucleotide 259 in the MTM1 gene was identified, predicted to result in an arg69-to-cys (R69C) amino acid substitution. The patient of <a href="#21" class="mim-tip-reference" title="Laporte, J., Guiraud-Chaumeil, C., Vincent, M.-C., Mandel, J.-L., Tanner, S. M., Liechti-Gallati, S., Wallgren-Pettersson, C., Dahl, N., Kress, W., Bolhuis, P. A., Fardeau, M., Samson, F., Bertini, E., members of the ENMC International Consortium on Myotubular Myopathy. <strong>Mutations in the MTM1 gene implicated in X-linked myotubular myopathy.</strong> Hum. Molec. Genet. 6: 1505-1511, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9305655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9305655</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9305655">Laporte et al. (1997)</a> was still alive at 3 years of age; 2 of the patients reported by <a href="#9" class="mim-tip-reference" title="de Gouyon, B. M., Zhao, W., Laporte, J., Mandel, J.-L., Metzenberg, A., Herman, G. E. <strong>Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy.</strong> Hum. Molec. Genet. 6: 1499-1504, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285787</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285787">de Gouyon et al. (1997)</a> were known to have had a mild phenotype and 1 of them had an affected uncle. This mutation was associated with a CpG dinucleotide. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9285787+9305655" 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 family with X-linked myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>), <a href="#27" class="mim-tip-reference" title="Tanner, S. M., Laporte, J., Guiraud-Chaumeil, C., Liechti-Gallati, S. <strong>Confirmation of prenatal diagnosis results of X-linked recessive myotubular myopathy by mutational screening, and description of three new mutations in the MTM1 gene.</strong> Hum. Mutat. 11: 62-68, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450905</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:1<62::AID-HUMU10>3.0.CO;2-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9450905">Tanner et al. (1998)</a> identified a G-to-A transition in the acceptor splice site of intron 8 (at nucleotide 733-1). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587783791 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587783791;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=rs587783791" 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=rs587783791" 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=RCV000011806 OR RCV002253197 OR RCV003335026 OR RCV004732461" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011806, RCV002253197, RCV003335026, RCV004732461" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011806...</a>
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<p>In a family with X-linked myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>), <a href="#27" class="mim-tip-reference" title="Tanner, S. M., Laporte, J., Guiraud-Chaumeil, C., Liechti-Gallati, S. <strong>Confirmation of prenatal diagnosis results of X-linked recessive myotubular myopathy by mutational screening, and description of three new mutations in the MTM1 gene.</strong> Hum. Mutat. 11: 62-68, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450905</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:1<62::AID-HUMU10>3.0.CO;2-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9450905">Tanner et al. (1998)</a> identified a 4-bp deletion (195delAGAA) leading to a frameshift at amino acid position 66. The mutation was expected to result in a premature stop codon and truncation of the MTM1 gene product. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397518445 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397518445;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=rs397518445" 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=rs397518445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a family with X-linked myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>), <a href="#27" class="mim-tip-reference" title="Tanner, S. M., Laporte, J., Guiraud-Chaumeil, C., Liechti-Gallati, S. <strong>Confirmation of prenatal diagnosis results of X-linked recessive myotubular myopathy by mutational screening, and description of three new mutations in the MTM1 gene.</strong> Hum. Mutat. 11: 62-68, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450905</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:1<62::AID-HUMU10>3.0.CO;2-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9450905">Tanner et al. (1998)</a> found that an A-to-G transition in intron 11 (nucleotide 1315-10) cosegregated with the haplotype associated with the MTM1 phenotype. It was presumed that a cryptic splice site existed at nucleotide position 1315-10. RT-PCR of muscle derived RNA from the patient and subsequent sequencing of the obtained products proved that splicing occurred at the new splice site. This predicted the insertion of 3 amino acids (FIQ) in frame between exon c and exon 12 in a conserved region of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450905" 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 the tabulation of <a href="#17" class="mim-tip-reference" title="Laporte, J., Biancalana, V., Tanner, S. M., Kress, W., Schneider, V., Wallgren-Pettersson, C., Herger, F., Buj-Bello, A., Blondeau, F., Liechti-Gallati, S., Mandel, J.-L. <strong>MTM1 mutations in X-linked myotubular myopathy.</strong> Hum. Mutat. 15: 393-409, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790201</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<393::AID-HUMU1>3.0.CO;2-R" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10790201">Laporte et al. (2000)</a>, this was the most frequent mutation found in the MTM1 gene in cases of X-linked myotubular myopathy and causes a severe myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011808 OR RCV000725013" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011808, RCV000725013" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011808...</a>
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<p>In the tabulation of <a href="#17" class="mim-tip-reference" title="Laporte, J., Biancalana, V., Tanner, S. M., Kress, W., Schneider, V., Wallgren-Pettersson, C., Herger, F., Buj-Bello, A., Blondeau, F., Liechti-Gallati, S., Mandel, J.-L. <strong>MTM1 mutations in X-linked myotubular myopathy.</strong> Hum. Mutat. 15: 393-409, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790201</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<393::AID-HUMU1>3.0.CO;2-R" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10790201">Laporte et al. (2000)</a>, the second most frequent recurrent mutation in the MTM1 gene in X-linked myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>) was a C-to-T transition at nucleotide 721, resulting in an arg241-to-cys amino acid substitution. The phenotype was mild in 5 patients (with 3 patients still alive at age 4 years) and severe in 2 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630306 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630306;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=rs132630306" 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=rs132630306" 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=RCV000011809 OR RCV004732462" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011809, RCV004732462" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011809...</a>
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<p><a href="#26" class="mim-tip-reference" title="Sutton, I. J., Winer, J. B., Norman, A. N., Liechti-Gallati, S., MacDonald, F. <strong>Limb girdle and facial weakness in female carriers of X-linked myotubular myopathy mutations.</strong> Neurology 57: 900-902, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11552027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11552027</a>] [<a href="https://doi.org/10.1212/wnl.57.5.900" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11552027">Sutton et al. (2001)</a> described a family with X-linked myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>) in which the index male was hemizygous for an arg224-to-ter (R224X) mutation in exon 8 of the MTM1 gene. The mother and maternal grandmother were obligate carriers according to linkage analysis, but neither showed any clinical manifestations of a myopathy. On the other hand, a maternal aunt had noted difficulty climbing stairs at the age of 5 years followed by progressive wasting and weakness of proximal limb muscles. Facial weakness beginning at the age of 8 years resulted in mild dysarthria. At the age of 13 years she was noted to have scoliosis. Examination at the age of 29 years showed bilateral facial weakness, proximal limb-girdle wasting and weakness, and bilateral weakness of the tibialis anterior. There was no weakness of extraocular movements. Creatine kinase was elevated at 203 IU/L. Although a skewed pattern of X-chromosome inactivation was suspected, such was detected in either the lymphocyte or muscle DNA of the woman, who was found to be heterozygous for the R224X mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11552027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#25" class="mim-tip-reference" title="Schara, U., Kress, W., Tucke, J., Mortier, W. <strong>X-linked myotubular myopathy in a female infant caused by a new MTM1 gene mutation.</strong> Neurology 60: 1363-1365, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707446</a>] [<a href="https://doi.org/10.1212/01.wnl.0000058763.90924.fa" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12707446">Schara et al. (2003)</a> reported a female with prenatal/neonatal onset of clinical symptoms due to myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>). During pregnancy, fetal movements were reduced. After birth, she showed severe hypotonia, dyspnea, a weak cry, absent tendon reflexes, a high-arched palate, and a right-sided ptosis. She later had limb-girdle and facial muscle weakness and a waddling gait. Skeletal muscle biopsy showed a wide variation of fiber size and numerous internal nuclei. Direct sequencing of the MTM1 gene showed a heterozygous frameshift mutation, 605delT. <a href="#25" class="mim-tip-reference" title="Schara, U., Kress, W., Tucke, J., Mortier, W. <strong>X-linked myotubular myopathy in a female infant caused by a new MTM1 gene mutation.</strong> Neurology 60: 1363-1365, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707446</a>] [<a href="https://doi.org/10.1212/01.wnl.0000058763.90924.fa" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12707446">Schara et al. (2003)</a> noted the more severe clinical course in this female compared to other reported affected females and emphasized the prenatal onset of symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12707446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630307 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630307;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=rs132630307" 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=rs132630307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a family with an unusually mild form of X-linked myotubular myopathy (CNMX; <a href="/entry/310400">310400</a>), as indicated by 3 males surviving into adulthood, <a href="#31" class="mim-tip-reference" title="Yu, S., Manson, J., White, S., Bourne, A., Waddy, H., Davis, M., Haan, E. <strong>X-linked myotubular myopathy in a family with three adult survivors.</strong> Clin. Genet. 64: 148-152, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12859411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12859411</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00118.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12859411">Yu et al. (2003)</a> identified a 469G-A transition in exon 7 of the MTM1 gene, resulting in a glu157-to-lys (E157K) substitution. There was no neonatal or infant mortality resulting from the myopathy. One affected male did not have neonatal asphyxia, had normal early motor milestones, and was able to increase his muscle mass and strength to normal by weight lifting. Another affected male, 55 years of age, lived independently. Two other families, each with a mild phenotype caused by a missense mutation in the MTM1 gene and multiple adult survivors, had previously been described (<a href="#1" class="mim-tip-reference" title="Barth, P. G., Dubowitz, V. <strong>X-linked myotubular myopathy--a long-term follow-up study.</strong> Europ. J. Paediat. Neurol. 2: 49-56, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10726846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10726846</a>] [<a href="https://doi.org/10.1016/1090-3798(98)01004-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10726846">Barth and Dubowitz, 1998</a>; <a href="#2" class="mim-tip-reference" title="Biancalana, V., Caron, O., Gallati, S., Baas, F., Kress, W., Novelli, G., D'Apice, M. R., Lagier-Tourenne, C., Buj-Bello, A., Romero, N. B., Mandel, J.-L. <strong>Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype.</strong> Hum. Genet. 112: 135-142, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522554</a>] [<a href="https://doi.org/10.1007/s00439-002-0869-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12522554">Biancalana et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10726846+12859411+12522554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Barth1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barth, P. G., Dubowitz, V.
|
|
<strong>X-linked myotubular myopathy--a long-term follow-up study.</strong>
|
|
Europ. J. Paediat. Neurol. 2: 49-56, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10726846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10726846</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10726846" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/1090-3798(98)01004-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Biancalana2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Biancalana, V., Caron, O., Gallati, S., Baas, F., Kress, W., Novelli, G., D'Apice, M. R., Lagier-Tourenne, C., Buj-Bello, A., Romero, N. B., Mandel, J.-L.
|
|
<strong>Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype.</strong>
|
|
Hum. Genet. 112: 135-142, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12522554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00439-002-0869-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Blondeau2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Blondeau, F., Laporte, J., Bodin, S., Superti-Furga, G., Payrastre, B., Mandel, J.-L.
|
|
<strong>Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway.</strong>
|
|
Hum. Molec. Genet. 9: 2223-2229, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11001925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11001925</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11001925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/oxfordjournals.hmg.a018913" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Buj-Bello1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Buj-Bello, A., Biancalana, V., Moutou, C., Laporte, J., Mandel, J.-L.
|
|
<strong>Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy.</strong>
|
|
Hum. Mutat. 14: 320-325, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<320::AID-HUMU7>3.0.CO;2-O" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Buj-Bello2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Buj-Bello, A., Laugel, V., Messaddeq, N., Zahreddine, H., Laporte, J., Pellissier, J.-F., Mandel, J.-L.
|
|
<strong>The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 15060-15065, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12391329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12391329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12391329[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12391329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.212498399" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Cowling2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cowling, B. S., Chevremont, T., Prokic, I., Kretz, C., Ferry, A., Coirault, C., Koutsopoulos, O., Laugel, V., Romero, N. B., Laporte, J.
|
|
<strong>Reducing dynamin 2 expression rescues X-linked centronuclear myopathy.</strong>
|
|
J. Clin. Invest. 124: 1350-1363, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24569376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24569376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24569376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24569376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI71206" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Cui1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cui, X., De Vivo, I., Slany, R., Miyamoto, A., Firestein, R., Cleary, M. L.
|
|
<strong>Association of SET domain and myotubularin-related proteins modulates growth control.</strong>
|
|
Nature Genet. 18: 331-337, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537414</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0498-331" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="de Gouyon1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Gouyon, B., Chatterjee, A., Monaco, A., Quaderi, N., Brown, S. D. M., Herman, G. E.
|
|
<strong>Comparative mapping on the mouse X chromosome defines a myotubular myopathy equivalent region.</strong>
|
|
Mammalian Genome 7: 575-579, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8678976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8678976</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8678976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s003359900172" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="de Gouyon1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Gouyon, B. M., Zhao, W., Laporte, J., Mandel, J.-L., Metzenberg, A., Herman, G. E.
|
|
<strong>Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy.</strong>
|
|
Hum. Molec. Genet. 6: 1499-1504, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285787</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9285787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/6.9.1499" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Dowling2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dowling, J. J., Vreede, A. P., Low, S. E., Gibbs, E. M., Kuwada, J. Y., Bonnemann, C. G., Feldman, E. L.
|
|
<strong>Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy.</strong>
|
|
PLoS Genet. 5: e1000372, 2009. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19197364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19197364</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19197364[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19197364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1371/journal.pgen.1000372" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Fetalvero2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fetalvero, K. M., Yu, Y., Goetschkes, M., Liang, G., Valdez, R. A., Gould, T., Triantafellow, E., Bergling, S., Loureiro, J., Eash, J., Lin, V., Porter, J. A., Finan, P. M., Walsh, K., Yang, Y., Mao, X., Murphy, L. O.
|
|
<strong>Defective autophagy and mTORC1 signaling in myotubularin null mice.</strong>
|
|
Molec. Cell. Biol. 33: 98-110, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23109424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23109424</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23109424[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23109424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.01075-12" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Guiraud-Chaumeil1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guiraud-Chaumeil, C., Vincent, M. C., Laporte, J., Fardeau, M., Samson, F., Mandel, J.-L.
|
|
<strong>A mutation in the MTM1 gene invalidates a previous suggestion of nonallelic heterogeneity in X-linked myotubular myopathy. (Letter)</strong>
|
|
Am. J. Hum. Genet. 60: 1542-1544, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199578</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/S0002-9297(07)64249-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Herman2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Herman, G. E., Kopacz, K., Zhao, W., Mills, P. L., Metzenberg, A., Das, S.
|
|
<strong>Characterization of mutations in fifty North American patients with X-linked myotubular myopathy.</strong>
|
|
Hum. Mutat. 19: 114-121, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11793470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11793470</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11793470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.10033" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Ketel2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ketel, K., Krauss, M., Nicot, A.-S., Puchkov, D., Wieffer, M., Muller, R., Subramanian, D., Schultz, C., Laporte, J., Haucke, V.
|
|
<strong>A phosphoinositide conversion mechanism for exit from endosomes.</strong>
|
|
Nature 529: 408-412, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26760201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26760201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26760201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature16516" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Kioschis1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kioschis, P., Rogner, U. C., Pick, E., Klauck, S. M., Heiss, N., Siebenhaar, R., Korn, B., Coy, J. F., Laporte, J., Liechti-Gallati, S., Poustka, A.
|
|
<strong>A 900-kb cosmid contig and 10 new transcripts within the candidate region for myotubular myopathy (MTM1).</strong>
|
|
Genomics 33: 365-373, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8660996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8660996</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8660996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1996.0212" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Kioschis1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kioschis, P., Wiemann, S., Heiss, N. S., Francis, F., Gotz, C., Poustka, A., Taudien, S., Platzer, M., Wiehe, T., Beckmann, G., Weber, J., Nordsiek, G., Rosenthal, A.
|
|
<strong>Genomic organization of a 225-kb region in Xq28 containing the gene for X-linked myotubular myopathy (MTM1) and a related gene (MTMR1).</strong>
|
|
Genomics 54: 256-266, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9828128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9828128</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9828128" 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/10.1006/geno.1998.5560" target="_blank">Full Text</a>]
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|
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|
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|
|
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|
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<a id="Laporte2000" class="mim-anchor"></a>
|
|
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|
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Laporte, J., Biancalana, V., Tanner, S. M., Kress, W., Schneider, V., Wallgren-Pettersson, C., Herger, F., Buj-Bello, A., Blondeau, F., Liechti-Gallati, S., Mandel, J.-L.
|
|
<strong>MTM1 mutations in X-linked myotubular myopathy.</strong>
|
|
Hum. Mutat. 15: 393-409, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<393::AID-HUMU1>3.0.CO;2-R" target="_blank">Full Text</a>]
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|
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|
|
<div class="">
|
|
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|
|
Laporte, J., Blondeau, F., Buj-Bello, A., Mandel, J.-L.
|
|
<strong>The myotubularin family: from genetic disease to phosphoinositide metabolism.</strong>
|
|
Trends Genet. 17: 221-228, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11275328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11275328</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11275328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1016/s0168-9525(01)02245-4" target="_blank">Full Text</a>]
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|
|
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|
|
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|
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<a id="Laporte1998" class="mim-anchor"></a>
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|
|
Laporte, J., Blondeau, F., Buj-Bello, A., Tentler, D., Kretz, C., Dahl, N., Mandel, J.-L.
|
|
<strong>Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human.</strong>
|
|
Hum. Molec. Genet. 7: 1703-1712, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9736772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9736772</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9736772" 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/7.11.1703" target="_blank">Full Text</a>]
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|
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|
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Laporte, J., Guiraud-Chaumeil, C., Tanner, S. M., Blondeau, F., Hu, L.-J., Vicaire, S., Liechti-Gallati, S., Mandel, J.-L.
|
|
<strong>Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy.</strong>
|
|
Europ. J. Hum. Genet. 6: 325-330, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9781038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9781038</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9781038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1038/sj.ejhg.5200189" target="_blank">Full Text</a>]
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<a id="Laporte1997" class="mim-anchor"></a>
|
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|
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Laporte, J., Guiraud-Chaumeil, C., Vincent, M.-C., Mandel, J.-L., Tanner, S. M., Liechti-Gallati, S., Wallgren-Pettersson, C., Dahl, N., Kress, W., Bolhuis, P. A., Fardeau, M., Samson, F., Bertini, E., members of the ENMC International Consortium on Myotubular Myopathy.
|
|
<strong>Mutations in the MTM1 gene implicated in X-linked myotubular myopathy.</strong>
|
|
Hum. Molec. Genet. 6: 1505-1511, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9305655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9305655</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9305655" 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/6.9.1505" target="_blank">Full Text</a>]
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|
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|
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|
|
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|
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|
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|
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Laporte, J., Hu, L. J., Kretz, C., Mandel, J.-L., Kioschis, P., Coy, J. F., Klauck, S. M., Poustka, A., Dahl, N.
|
|
<strong>A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.</strong>
|
|
Nature Genet. 13: 175-182, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640223</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8640223" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1038/ng0696-175" target="_blank">Full Text</a>]
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|
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|
|
</li>
|
|
|
|
<li>
|
|
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|
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|
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|
|
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|
|
Nandurkar, H. H., Layton, M., Laporte, J., Selan, C., Corcoran, L., Caldwell, K. K., Mochizuki, Y., Majerus, P. W., Mitchell, C. A.
|
|
<strong>Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter (sic) protein, 3-PAP.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 8660-8665, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12847286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12847286</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12847286[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12847286" 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/10.1073/pnas.1033097100" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
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|
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|
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|
|
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|
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Samson, F., Mesnard, L., Heimburger, M., Hanauer, A., Chevallay, M., Mercadier, J. J., Pelissier, J. F., Feingold, N., Junien, C., Mandel, J.-L., Fardeau, M.
|
|
<strong>Genetic linkage heterogeneity in myotubular myopathy.</strong>
|
|
Am. J. Hum. Genet. 57: 120-126, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7611280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7611280</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7611280" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
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|
|
|
|
<li>
|
|
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|
|
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|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schara, U., Kress, W., Tucke, J., Mortier, W.
|
|
<strong>X-linked myotubular myopathy in a female infant caused by a new MTM1 gene mutation.</strong>
|
|
Neurology 60: 1363-1365, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12707446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1212/01.wnl.0000058763.90924.fa" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
<p class="mim-text-font">
|
|
Sutton, I. J., Winer, J. B., Norman, A. N., Liechti-Gallati, S., MacDonald, F.
|
|
<strong>Limb girdle and facial weakness in female carriers of X-linked myotubular myopathy mutations.</strong>
|
|
Neurology 57: 900-902, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11552027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11552027</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11552027" 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.57.5.900" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
Tanner, S. M., Laporte, J., Guiraud-Chaumeil, C., Liechti-Gallati, S.
|
|
<strong>Confirmation of prenatal diagnosis results of X-linked recessive myotubular myopathy by mutational screening, and description of three new mutations in the MTM1 gene.</strong>
|
|
Hum. Mutat. 11: 62-68, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450905</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450905" 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/(SICI)1098-1004(1998)11:1<62::AID-HUMU10>3.0.CO;2-X" target="_blank">Full Text</a>]
|
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|
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|
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|
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|
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|
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|
|
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|
|
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|
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Taylor, G. S., Maehama, T., Dixon, J. E.
|
|
<strong>Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 8910-8915, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10900271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10900271</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10900271[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10900271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1073/pnas.160255697" target="_blank">Full Text</a>]
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|
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|
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|
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|
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Tsai, T.-C., Horinouchi, H., Noguchi, S., Minami, N., Murayama, K., Hayashi, Y. K., Nonaka, I., Nishino, I.
|
|
<strong>Characterization of MTM1 mutations in 31 Japanese families with myotubular myopathy, including a patient carrying 240 kb deletion in Xq28 without male hypogenitalism.</strong>
|
|
Neuromusc. Disord. 15: 245-252, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15725586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15725586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15725586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2004.12.005" target="_blank">Full Text</a>]
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Van Wijngaarden, G. K., Fleury, P., Bethlem, J., Meijer, A. E. F. H.
|
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<strong>Familial 'myotubular' myopathy.</strong>
|
|
Neurology 19: 901-908, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5816884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5816884</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5816884" 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.19.9.901" target="_blank">Full Text</a>]
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Yu, S., Manson, J., White, S., Bourne, A., Waddy, H., Davis, M., Haan, E.
|
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<strong>X-linked myotubular myopathy in a family with three adult survivors.</strong>
|
|
Clin. Genet. 64: 148-152, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12859411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12859411</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12859411" 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/10.1034/j.1399-0004.2003.00118.x" target="_blank">Full Text</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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Ada Hamosh - updated : 12/14/2016
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Cassandra L. Kniffin - updated : 12/15/2014<br>Patricia A. Hartz - updated : 10/31/2013<br>Cassandra L. Kniffin - updated : 6/5/2009<br>Cassandra L. Kniffin - updated : 4/11/2005<br>Victor A. McKusick - updated : 8/28/2003<br>Victor A. McKusick - updated : 8/20/2003<br>Cassandra L. Kniffin - updated : 6/16/2003<br>Victor A. McKusick - updated : 1/14/2003
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Creation Date:
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Cassandra L. Kniffin : 12/11/2002
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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mgross : 05/14/2021
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alopez : 12/14/2016<br>alopez : 12/22/2014<br>alopez : 12/16/2014<br>mcolton : 12/15/2014<br>ckniffin : 12/15/2014<br>mgross : 11/7/2013<br>mcolton : 11/1/2013<br>mcolton : 10/31/2013<br>carol : 9/1/2010<br>wwang : 6/23/2009<br>wwang : 6/22/2009<br>ckniffin : 6/5/2009<br>wwang : 4/25/2005<br>ckniffin : 4/11/2005<br>cwells : 9/3/2003<br>terry : 8/28/2003<br>tkritzer : 8/27/2003<br>tkritzer : 8/25/2003<br>terry : 8/20/2003<br>carol : 6/16/2003<br>ckniffin : 6/11/2003<br>carol : 1/23/2003<br>carol : 1/23/2003<br>tkritzer : 1/17/2003<br>terry : 1/14/2003<br>carol : 12/17/2002<br>ckniffin : 12/12/2002
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<strong>*</strong> 300415
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MYOTUBULARIN; MTM1
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<strong><em>HGNC Approved Gene Symbol: MTM1</em></strong>
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<strong>SNOMEDCT:</strong> 46804001;
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<strong>ICD10CM:</strong> G71.220;
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Cytogenetic location: Xq28
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Genomic coordinates <span class="small">(GRCh38)</span> : X:150,562,653-150,673,143 </span>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Xq28
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Myopathy, centronuclear, X-linked
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310400
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X-linked recessive
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The MTM1 gene encodes a protein that belongs to a family of putative tyrosine phosphatases. Myotubularin is required for muscle cell differentiation. Myotubularin is also a potent phosphatidylinositol 3-phosphate (PI3P) phosphatase (Blondeau et al., 2000; Taylor et al., 2000). </p><p>According to Laporte et al. (1998), 8 different genes encoding human myotubularin-related proteins had been reported: MTMR1 (300171) on Xq28; MTMR2 (603557) on 11q22; MTMR3 (603558) on 22q12; MTMR4 (603559) on chromosome 17; SBF1, also known as MTMR5 (603560), on 22qter; MTMR6 (603561) on 13q12; MTMR7 (603562) on 8p22; and MTMR8 (MTMR9; 606260) on 8p23-p22. </p>
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<strong>Cloning and Expression</strong>
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<p>A consortium of 3 groups (Laporte et al., 1996) reported the isolation and characterization of the MTM1 gene (Laporte et al., 1996). They restricted the candidate region for the gene mutated in X-linked myotubular myopathy-1 (XLMTM; 310400) to 280 kb and then used positional cloning to characterize a 3.4-kb cDNA that encodes at least 621 amino acids and a polyadenylation site. Additional clones from liver and skeletal muscle showed an alternative upstream polyadenylation site. The protein encoded by the MTM1 gene, designated myotubularin, was found to be highly conserved in yeast. The protein contains the consensus sequence for the active site of tyrosine phosphatases, a wide class of proteins involved in signal transduction. Preliminary Northern analysis showed ubiquitous expression of a 3.9-kb MTM1 transcript, while a 2.4-kb message was detected in skeletal muscle and testis. Both the high conservation in yeast and the ubiquitous expression of the MTM1 transcript contrasted strikingly with the apparent muscle specificity of the disease myotubular myopathy. Laporte et al. (1996) stated that at least 3 other genes, 1 located within 100 kb distal from the MTM1 gene, encode proteins with very high sequence similarities and define, together with the MTM1 gene, a new family of putative tyrosine phosphatases (PTPs) in man. Kioschis et al. (1996) constructed a 900-kb cosmid contig including the entire MTM1 candidate region and identified 10 new transcripts within the region. </p>
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<strong>Mapping</strong>
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<p>By positional cloning, Laporte et al. (1996) mapped the MTM1 gene to Xq28. </p><p>Kioschis et al. (1998) determined that the MTM1 and MTMR1 genes are transcribed in the same direction and are separated by 20 kb. Analysis of the genomic region containing MTM1 and MTMR1 suggested that the 2 genes are related and arose from an intrachromosomal gene duplication. The authors stated that other examples of intrachromosomal gene duplication in Xq28 include the IDS (300823) gene duplication and a cluster of MAGE genes (see 300016). </p><p>As part of an effort to clone the MTM1 gene, de Gouyon et al. (1996) developed a YAC contig of the mouse X chromosome which included loci homologous to those within the human MTM1 critical region, a 300-kb interval between IDS (300823) and GABRA3 (305660) on Xq28. They aligned the human and murine physical maps by isolating conserved mouse genomic fragments, including CpG islands and trapped exons. </p>
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<strong>Gene Function</strong>
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<p>The SET (Suvar3-9, Enhancer of zeste, trithorax) domain was originally identified as a characteristic motif in several Drosophila proteins that contribute to epigenetic mechanisms of gene regulation. The human protooncoprotein HRX (159555) also contains a SET domain. Cui et al. (1998) determined that MTM1 and SBF1 (603560) interacted with HRX in vitro and in vivo. This interaction was abrogated in an oncogenic form of HRX lacking the SET domain. Like HRX, both SBF1 and MTM1 localized to the nucleus of mammalian cells. The authors found that MTM1 and SBF1 have a conserved SET interaction domain (SID) that displays a paired amphipathic helix secondary structure. In contrast with MTM1, SBF1 lacked dual-specificity phosphatase activity in vitro, suggesting that SBF1 acts as a protective factor that prevents substrate dephosphorylation. Ectopic expression of SBF1 impaired the in vitro differentiation of myoblast cells, implying that interactions of SET-domain proteins with catalytically active members of the myotubularin family are essential for execution of the myogenic program. The authors stated that these results are consistent with the adverse effects of inherited MTM1 loss-of-function mutations on muscle maturation in X-linked myotubular myopathy (XLMTM). They concluded that myotubularin proteins link SET domain-containing components of the epigenetic regulatory machinery with signaling pathways involved in differentiation. </p><p>Taylor et al. (2000) reported that myotubularin, a protein-tyrosine phosphatase required for muscle cell differentiation, is a potent phosphatidylinositol 3-phosphate (PI3P) phosphatase. They found that mutations in the MTM1 gene that cause human myotubular myopathy dramatically reduced the ability of the phosphatase to dephosphorylate PI3P. The findings provided evidence that myotubularin exerts its effects during myogenesis by regulating the cellular levels of the inositol lipid PI3P. </p><p>Blondeau et al. (2000) investigated the activity and substrate specificity of MTM1. Expression of active human myotubularin inhibited growth of S. pombe and induced a vacuolar phenotype similar to that of mutants of the vacuolar protein sorting (VPS) pathway and notably of mutants of VPS34, a phosphatidylinositol 3-kinase (PI3K; see 602838). In S. pombe cells deleted for the endogenous MTM homologous gene, expression of human myotubularin decreased the level of phosphatidylinositol 3-phosphate (PI3P). A substrate trap mutant relocalized to plasma membrane projections (spikes) in HeLa cells and was inactive in the S. pombe assay. This mutant, but not the wildtype or a phosphatase site mutant, was able to immunoprecipitate a VPS34 kinase activity. Wildtype myotubularin was also able to directly dephosphorylate PI3P and PI4P in vitro. The authors hypothesized that myotubularin may decrease PI3P levels by downregulating PI3K activity and by directly degrading PI3P. </p><p>Laporte et al. (2001) provided an extensive review of the myotubularin-related genes. These genes define a large family of eukaryotic proteins, most of which were initially characterized by the presence of a 10-amino acid consensus sequence related to the active sites of tyrosine phosphatases, dual-specificity protein phosphatases, and the lipid phosphatase PTEN (601728). MTM1 is the founding member of the family. A close homolog, MTMR2 (603557), is mutated in a recessive form of Charcot-Marie-Tooth neuropathy (601382). Laporte et al. (2001) pointed out that although myotubularin was thought to be a dual-specificity protein phosphatase, studies indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and possibly involved in the regulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking. </p><p>Nandurkar et al. (2003) identified myotubularin as the catalytically active 3-phosphatase subunit interacting with 3PAP (606501). Recombinant myotubularin localized to the plasma membrane, causing extensive filopodia formation. However, coexpression of 3PAP with myotubularin led to attenuation of the plasma membrane phenotype, associated with myotubularin relocalization to the cytosol. Collectively these studies indicated that 3PAP functions as an 'adaptor' for myotubularin, regulating myotubularin intracellular location and thereby altering the phenotype resulting from myotubularin overexpression. </p><p>Ketel et al. (2016) reported that surface delivery of endosomal cargo requires hydrolysis of PI(3)P by the phosphatidylinositol 3-phosphatase MTM1, an enzyme whose loss of function leads to X-linked centronuclear myopathy (also called myotubular myopathy) in humans. Removal of endosomal PI(3)P by MTM1 is accompanied by phosphatidylinositol 4-kinase-2-alpha (PI4K2-alpha)-dependent generation of PI(4)P and recruitment of the exocyst tethering complex to enable membrane fusion. Ketel et al. (2016) concluded that their data established a mechanism for phosphoinositide conversion from PI(3)P to PI(4)P at endosomes en route to the plasma membrane and suggested that defective phosphoinositide conversion at endosomes underlies X-linked centronuclear myopathy caused by mutation of MTM1 in humans. </p>
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<strong>Molecular Genetics</strong>
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<p>In a male with XLMTM, Laporte et al. (1996) demonstrated an A-to-G transition at nucleotide 620 predicting a substitution of serine for asparagine-207 in the MTM1 gene (300415.0001). This was 1 of 4 missense mutations that, together with 3 frameshift mutations, were found in 7 of 60 MTM1 patients studied. </p><p>By direct genomic sequencing of 92% of the known coding sequence of the myotubularin gene, de Gouyon et al. (1997) identified mutations in 26 of 41 unrelated male patients with muscle biopsy-proven myotubular myopathy. Point mutations were found in 18 patients, including an A-to-G transition found in 4 patients, which altered a splice acceptor site in exon 12 and led to a 3-amino acid insertion. Six patients had small deletions involving less than 6 bp, while 2 larger deletions encompassed 2 and 6 exons, respectively. All 5 patients with a mild phenotype had missense mutations (e.g., 300415.0003). While 50% of the mutations were found in exons 4 and 12, and 3 distinct mutations were found in more than 1 patient, no single mutation accounted for more than 10% of the cases. Low frequency of large deletions and the varied mutations identified suggested to de Gouyon et al. (1997) that direct mutation screening for molecular diagnosis may require gene sequencing. </p><p>Simultaneously, a consortium of 3 groups of investigators (Laporte et al., 1997) reported the identification of MTM1 mutations in 55 of 85 unrelated patients screened by SSCP for all the coding sequence. Large deletions were observed in only 3 patients. Five point mutations were found in multiple unrelated patients, accounting for 27% of the observed mutations. More than half of the mutations were expected to inactivate the putative enzymatic activity of myotubularin, either by truncation or by missense mutations affecting the predicted protein tyrosine phosphatase domain. Laporte et al. (1997) suggested that there are likely to be other functional domains of the protein since additional missense mutations were clustered in 2 regions of the protein where the affected amino acids are conserved in yeast and C. elegans. </p><p>In 3 families previously investigated by linkage analysis, Tanner et al. (1998) identified 3 new mutations in the MTM1 gene as the cause of X-linked recessive myotubular myopathy: an acceptor splice site mutation (300415.0004), a frameshift mutation (300415.0005), and an intronic mutation involving a cryptic splice site (300415.0006). </p><p>Buj-Bello et al. (1999) reported the identification of 21 mutations (14 novel) in XLMTM patients. Seventeen mutations were associated with a severe phenotype. The other 4 mutations (3 missense and 1 single-amino acid deletion) were found in patients with a much milder phenotype; although all of them had severe hypotonia at birth, the hypotonia improved with age. </p><p>Laporte et al. (1998) determined intronic flanking sequences for all 15 exons of the MTM1 gene to facilitate the detection of mutations in patients and genetic counseling. They characterized a new polymorphic marker in the immediate vicinity of the gene that might prove useful for linkage analysis. Laporte et al. (2000) reported 29 mutations in cases of myotubular myopathy, including 16 novel mutations. They stated that 198 mutations had been identified in unrelated families, accounting for 133 different disease-associated mutations widely distributed throughout the gene. Most of the point mutations were truncating, but 26% (35 of 133) were missense mutations affecting residues conserved in the Drosophila ortholog and in the homologous MTMR1 gene. Three recurrent mutations affected 17% of the patients, and a total of 21 mutations were found in several independent families. The frequency of female carriers appeared higher than expected; only 17% were de novo mutations. Whereas most truncating mutations caused a severe and early lethal phenotype, some missense mutations were associated with milder forms and prolonged survival, up to 54 years in the first reported family (Van Wijngaarden et al., 1969; Barth and Dubowitz, 1998). </p><p>Herman et al. (2002) stated that 133 different mutations had been identified in the MTM1 gene worldwide. They reported mutations detected in 50 additional U.S. families with biopsy-proven MTM1. Eighteen novel mutations were identified in 41 patients who had not previously been described. Eighty-eight percent of the mothers of sporadic cases studied were identified as carriers. </p><p>Tsai et al. (2005) reported 31 Japanese patients with myotubular myopathy caused by mutation in the MTM1 gene, and identified 14 novel mutations. Truncating mutations and gene-abolishing large deletions accounted for 52% of the mutations. A splice site mutation (300415.0006) was identified in 3 unrelated patients, suggesting it is a mutation hotspot. </p>
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<p>To understand the pathophysiologic mechanism of XLMTM, Buj-Bello et al. (2002) generated mice lacking myotubularin by homologous recombination. These mice were viable, but their life span was severely reduced. They developed a generalized and progressive myopathy starting at approximately 4 weeks of age, with amyotrophy and accumulation of central nuclei in skeletal muscle fibers leading to death at 6 to 14 weeks of age. Buj-Bello et al. (2002) showed that muscle differentiation in knockout mice occurred normally, contrary to expectations. They provided evidence that fibers with centralized myonuclei originate mainly from a structural maintenance defect affecting myotubularin-deficient muscle rather than a regenerative process. In addition, they demonstrated through a conditional gene-targeting approach that skeletal muscle is the primary target of murine XLMTM pathology. </p><p>Dowling et al. (2009) observed that zebrafish with reduced levels of myotubularin had significantly impaired motor function and obvious histopathologic muscle changes, including abnormally shaped and positioned nuclei and myofiber hypotrophy, as observed in the human disease. Loss of myotubularin caused increased PI3P levels in muscle in vivo. Morpholino knockdown of Mtm1 in zebrafish muscle resulted in abnormalities in the T-tubule and sarcoplasmic reticulum network, similar to T-tubule disorganization observed in patients with myotubular myopathy. Expression of the homologous myotubularin-related proteins Mtmr1 and Mtmr2 could functionally compensate for the loss of myotubularin in zebrafish. Dowling et al. (2009) suggested that XLMTM may be linked mechanistically by tubuloreticular abnormalities and defective excitation-contraction coupling to myopathies caused by mutations in the RYR1 gene (180901). </p><p>Fetalvero et al. (2013) found that Mtm1 -/- skeletal muscle showed increased content of PI3P, ubiquitinated proteins, and lipidated proteins normally degraded via autophagy. Mtm1 -/- skeletal muscle also showed accumulation of defective mitochondria with decreased COX enzyme activity and elevated activity of mTORC1 (see 601231), a major nutrient sensor and autophagy inhibitor. No change in mTORC1, mitochondria, or content of nondegraded proteins was observed in liver, heart, or brain of Mtm1 -/- mice. Overnight fasting activated mTORC1-dependent inhibition of autophagy in wildtype, but not Mtm1 -/-, skeletal muscle. Inhibition of hyperactivated mTORC1 normalized autophagy and rescued muscle mass in Mtm1 -/- mice. Fetalvero et al. (2013) concluded that MTM1 is involved in regulation of mTORC1 and autophagy. </p><p>Cowling et al. (2014) found a 1.5-fold increase in DNM2 (602378) expression in muscle biopsies isolated from human patients with CNMX (XLMTM) and in heterozygous Mtm1 -/y mice compared to controls. Crossing Mtm1 -/y with Dnm2 +/- mice resulted in increased survival and greatly improved muscle strength, suggesting that reduced expression of the Dnm2 gene can rescue the early lethality observed in Mtm1 -/y mice. Skeletal muscle from the double-mutant mice showed decreased or even rescued atrophy compared to Mtm1 -/y mice, and histologic abnormalities such as fiber atrophy and nuclei mispositioning were absent or reduced in the double-mutant mice. Ultrastructural analysis showed improvement of sarcomere organization and triad structures. In addition, muscle-specific reduction of Dnm2, particularly in the diaphragm, was sufficient to rescue the lethal phenotype even after birth and the onset of symptoms. The findings indicated that MTM1 and DNM2 regulate muscle organization and force through a common pathway, and suggested that MTM1 may act as a negative regulator of DNM2. Cowling et al. (2014) concluded that reduction of DNM2 protein levels may provide a therapeutic approach for patients with CNMX. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>10 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MYOTUBULAR MYOPATHY, X-LINKED</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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MTM1, ASN207SER
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<br />
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SNP: rs132630302,
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ClinVar: RCV000011802, RCV004700217
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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 X-linked myotubular myopathy (CNMX; 310400), Laporte et al. (1996) demonstrated an A-to-G transition of nucleotide 620 predicting a substitution of serine for asparagine-207 in the MTM1 gene. This was 1 of 4 missense mutations that, together with 3 frameshift mutations, were found in 7 of 60 MTM1 patients studied. </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>.0002 MYOTUBULAR MYOPATHY, X-LINKED</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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MTM1, TYR415CYS
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<br />
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SNP: rs132630303,
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ClinVar: RCV000011803
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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 an affected individual thought to have a form of X-linked myotubular myopathy (CNMX; 310400) distinct from the Xq28 form (Samson et al., 1995), Guiraud-Chaumeil et al. (1997) found a single basepair change, 1244A-G, resulting in a change of tyrosine-415 to cysteine in the predicted protein (called myotubularin by them). This tyrosine coded in exon c (Laporte et al., 1996) is close to the putative tyrosine phosphatase active site (positions 389 to 402) and is conserved in the homologs of myotubularin in both yeast and C. elegans. </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>.0003 MYOTUBULAR MYOPATHY, X-LINKED</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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MTM1, ARG69CYS
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<br />
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SNP: rs132630304,
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ClinVar: RCV000011804, RCV003441713, RCV004732460
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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 3 patients with X-linked myotubular myopathy (CNMX; 310400) studied by de Gouyon et al. (1997) and in 1 patient studied by Laporte et al. (1997), a C-to-T transition of nucleotide 259 in the MTM1 gene was identified, predicted to result in an arg69-to-cys (R69C) amino acid substitution. The patient of Laporte et al. (1997) was still alive at 3 years of age; 2 of the patients reported by de Gouyon et al. (1997) were known to have had a mild phenotype and 1 of them had an affected uncle. This mutation was associated with a CpG dinucleotide. </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>.0004 MYOTUBULAR MYOPATHY, X-LINKED</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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MTM1, IVS8, G-A, -1
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<br />
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SNP: rs672601324,
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ClinVar: RCV000011805
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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 family with X-linked myotubular myopathy (CNMX; 310400), Tanner et al. (1998) identified a G-to-A transition in the acceptor splice site of intron 8 (at nucleotide 733-1). </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>.0005 MYOTUBULAR MYOPATHY, X-LINKED</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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MTM1, 4-BP DEL, NT195
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<br />
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SNP: rs587783791,
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ClinVar: RCV000011806, RCV002253197, RCV003335026, RCV004732461
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a family with X-linked myotubular myopathy (CNMX; 310400), Tanner et al. (1998) identified a 4-bp deletion (195delAGAA) leading to a frameshift at amino acid position 66. The mutation was expected to result in a premature stop codon and truncation of the MTM1 gene product. </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>.0006 MYOTUBULAR MYOPATHY, X-LINKED</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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|
|
MTM1, IVS11, A-G, -10
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<br />
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|
SNP: rs397518445,
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|
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ClinVar: RCV000011807, RCV000255138, RCV004585996, RCV004739300
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with X-linked myotubular myopathy (CNMX; 310400), Tanner et al. (1998) found that an A-to-G transition in intron 11 (nucleotide 1315-10) cosegregated with the haplotype associated with the MTM1 phenotype. It was presumed that a cryptic splice site existed at nucleotide position 1315-10. RT-PCR of muscle derived RNA from the patient and subsequent sequencing of the obtained products proved that splicing occurred at the new splice site. This predicted the insertion of 3 amino acids (FIQ) in frame between exon c and exon 12 in a conserved region of the protein. </p><p>In the tabulation of Laporte et al. (2000), this was the most frequent mutation found in the MTM1 gene in cases of X-linked myotubular myopathy and causes a severe myopathy. </p>
|
|
</span>
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|
</div>
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MYOTUBULAR MYOPATHY, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTM1, ARG241CYS
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|
|
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|
|
<br />
|
|
|
|
SNP: rs132630305,
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|
|
|
|
|
|
|
ClinVar: RCV000011808, RCV000725013
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the tabulation of Laporte et al. (2000), the second most frequent recurrent mutation in the MTM1 gene in X-linked myotubular myopathy (CNMX; 310400) was a C-to-T transition at nucleotide 721, resulting in an arg241-to-cys amino acid substitution. The phenotype was mild in 5 patients (with 3 patients still alive at age 4 years) and severe in 2 patients. </p>
|
|
</span>
|
|
</div>
|
|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MYOTUBULAR MYOPATHY, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTM1, ARG224TER
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|
<br />
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|
|
SNP: rs132630306,
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|
|
|
|
|
ClinVar: RCV000011809, RCV004732462
|
|
|
|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Sutton et al. (2001) described a family with X-linked myotubular myopathy (CNMX; 310400) in which the index male was hemizygous for an arg224-to-ter (R224X) mutation in exon 8 of the MTM1 gene. The mother and maternal grandmother were obligate carriers according to linkage analysis, but neither showed any clinical manifestations of a myopathy. On the other hand, a maternal aunt had noted difficulty climbing stairs at the age of 5 years followed by progressive wasting and weakness of proximal limb muscles. Facial weakness beginning at the age of 8 years resulted in mild dysarthria. At the age of 13 years she was noted to have scoliosis. Examination at the age of 29 years showed bilateral facial weakness, proximal limb-girdle wasting and weakness, and bilateral weakness of the tibialis anterior. There was no weakness of extraocular movements. Creatine kinase was elevated at 203 IU/L. Although a skewed pattern of X-chromosome inactivation was suspected, such was detected in either the lymphocyte or muscle DNA of the woman, who was found to be heterozygous for the R224X mutation. </p>
|
|
</span>
|
|
</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>.0009 MYOTUBULAR MYOPATHY, X-LINKED</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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MTM1, 1-BP DEL, 605T
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<br />
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SNP: rs672601325,
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|
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|
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ClinVar: RCV000011810
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|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Schara et al. (2003) reported a female with prenatal/neonatal onset of clinical symptoms due to myotubular myopathy (CNMX; 310400). During pregnancy, fetal movements were reduced. After birth, she showed severe hypotonia, dyspnea, a weak cry, absent tendon reflexes, a high-arched palate, and a right-sided ptosis. She later had limb-girdle and facial muscle weakness and a waddling gait. Skeletal muscle biopsy showed a wide variation of fiber size and numerous internal nuclei. Direct sequencing of the MTM1 gene showed a heterozygous frameshift mutation, 605delT. Schara et al. (2003) noted the more severe clinical course in this female compared to other reported affected females and emphasized the prenatal onset of symptoms. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MYOTUBULAR MYOPATHY, X-LINKED</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
MTM1, GLU157LYS
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<br />
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SNP: rs132630307,
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ClinVar: RCV000011811, RCV004589504
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with an unusually mild form of X-linked myotubular myopathy (CNMX; 310400), as indicated by 3 males surviving into adulthood, Yu et al. (2003) identified a 469G-A transition in exon 7 of the MTM1 gene, resulting in a glu157-to-lys (E157K) substitution. There was no neonatal or infant mortality resulting from the myopathy. One affected male did not have neonatal asphyxia, had normal early motor milestones, and was able to increase his muscle mass and strength to normal by weight lifting. Another affected male, 55 years of age, lived independently. Two other families, each with a mild phenotype caused by a missense mutation in the MTM1 gene and multiple adult survivors, had previously been described (Barth and Dubowitz, 1998; Biancalana et al., 2003). </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>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barth, P. G., Dubowitz, V.
|
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<strong>X-linked myotubular myopathy--a long-term follow-up study.</strong>
|
|
Europ. J. Paediat. Neurol. 2: 49-56, 1998.
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|
[PubMed: 10726846]
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[Full Text: https://doi.org/10.1016/1090-3798(98)01004-9]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Biancalana, V., Caron, O., Gallati, S., Baas, F., Kress, W., Novelli, G., D'Apice, M. R., Lagier-Tourenne, C., Buj-Bello, A., Romero, N. B., Mandel, J.-L.
|
|
<strong>Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype.</strong>
|
|
Hum. Genet. 112: 135-142, 2003.
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[PubMed: 12522554]
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[Full Text: https://doi.org/10.1007/s00439-002-0869-1]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Blondeau, F., Laporte, J., Bodin, S., Superti-Furga, G., Payrastre, B., Mandel, J.-L.
|
|
<strong>Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway.</strong>
|
|
Hum. Molec. Genet. 9: 2223-2229, 2000.
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[PubMed: 11001925]
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[Full Text: https://doi.org/10.1093/oxfordjournals.hmg.a018913]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Buj-Bello, A., Biancalana, V., Moutou, C., Laporte, J., Mandel, J.-L.
|
|
<strong>Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy.</strong>
|
|
Hum. Mutat. 14: 320-325, 1999.
|
|
|
|
|
|
[PubMed: 10502779]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<320::AID-HUMU7>3.0.CO;2-O]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Buj-Bello, A., Laugel, V., Messaddeq, N., Zahreddine, H., Laporte, J., Pellissier, J.-F., Mandel, J.-L.
|
|
<strong>The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 15060-15065, 2002.
|
|
|
|
|
|
[PubMed: 12391329]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.212498399]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cowling, B. S., Chevremont, T., Prokic, I., Kretz, C., Ferry, A., Coirault, C., Koutsopoulos, O., Laugel, V., Romero, N. B., Laporte, J.
|
|
<strong>Reducing dynamin 2 expression rescues X-linked centronuclear myopathy.</strong>
|
|
J. Clin. Invest. 124: 1350-1363, 2014.
|
|
|
|
|
|
[PubMed: 24569376]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI71206]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cui, X., De Vivo, I., Slany, R., Miyamoto, A., Firestein, R., Cleary, M. L.
|
|
<strong>Association of SET domain and myotubularin-related proteins modulates growth control.</strong>
|
|
Nature Genet. 18: 331-337, 1998.
|
|
|
|
|
|
[PubMed: 9537414]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0498-331]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Gouyon, B., Chatterjee, A., Monaco, A., Quaderi, N., Brown, S. D. M., Herman, G. E.
|
|
<strong>Comparative mapping on the mouse X chromosome defines a myotubular myopathy equivalent region.</strong>
|
|
Mammalian Genome 7: 575-579, 1996.
|
|
|
|
|
|
[PubMed: 8678976]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s003359900172]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Gouyon, B. M., Zhao, W., Laporte, J., Mandel, J.-L., Metzenberg, A., Herman, G. E.
|
|
<strong>Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy.</strong>
|
|
Hum. Molec. Genet. 6: 1499-1504, 1997.
|
|
|
|
|
|
[PubMed: 9285787]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/6.9.1499]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dowling, J. J., Vreede, A. P., Low, S. E., Gibbs, E. M., Kuwada, J. Y., Bonnemann, C. G., Feldman, E. L.
|
|
<strong>Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy.</strong>
|
|
PLoS Genet. 5: e1000372, 2009. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 19197364]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1371/journal.pgen.1000372]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fetalvero, K. M., Yu, Y., Goetschkes, M., Liang, G., Valdez, R. A., Gould, T., Triantafellow, E., Bergling, S., Loureiro, J., Eash, J., Lin, V., Porter, J. A., Finan, P. M., Walsh, K., Yang, Y., Mao, X., Murphy, L. O.
|
|
<strong>Defective autophagy and mTORC1 signaling in myotubularin null mice.</strong>
|
|
Molec. Cell. Biol. 33: 98-110, 2013.
|
|
|
|
|
|
[PubMed: 23109424]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.01075-12]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guiraud-Chaumeil, C., Vincent, M. C., Laporte, J., Fardeau, M., Samson, F., Mandel, J.-L.
|
|
<strong>A mutation in the MTM1 gene invalidates a previous suggestion of nonallelic heterogeneity in X-linked myotubular myopathy. (Letter)</strong>
|
|
Am. J. Hum. Genet. 60: 1542-1544, 1997.
|
|
|
|
|
|
[PubMed: 9199578]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0002-9297(07)64249-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Herman, G. E., Kopacz, K., Zhao, W., Mills, P. L., Metzenberg, A., Das, S.
|
|
<strong>Characterization of mutations in fifty North American patients with X-linked myotubular myopathy.</strong>
|
|
Hum. Mutat. 19: 114-121, 2002.
|
|
|
|
|
|
[PubMed: 11793470]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10033]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ketel, K., Krauss, M., Nicot, A.-S., Puchkov, D., Wieffer, M., Muller, R., Subramanian, D., Schultz, C., Laporte, J., Haucke, V.
|
|
<strong>A phosphoinositide conversion mechanism for exit from endosomes.</strong>
|
|
Nature 529: 408-412, 2016.
|
|
|
|
|
|
[PubMed: 26760201]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature16516]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kioschis, P., Rogner, U. C., Pick, E., Klauck, S. M., Heiss, N., Siebenhaar, R., Korn, B., Coy, J. F., Laporte, J., Liechti-Gallati, S., Poustka, A.
|
|
<strong>A 900-kb cosmid contig and 10 new transcripts within the candidate region for myotubular myopathy (MTM1).</strong>
|
|
Genomics 33: 365-373, 1996.
|
|
|
|
|
|
[PubMed: 8660996]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0212]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kioschis, P., Wiemann, S., Heiss, N. S., Francis, F., Gotz, C., Poustka, A., Taudien, S., Platzer, M., Wiehe, T., Beckmann, G., Weber, J., Nordsiek, G., Rosenthal, A.
|
|
<strong>Genomic organization of a 225-kb region in Xq28 containing the gene for X-linked myotubular myopathy (MTM1) and a related gene (MTMR1).</strong>
|
|
Genomics 54: 256-266, 1998.
|
|
|
|
|
|
[PubMed: 9828128]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1998.5560]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laporte, J., Biancalana, V., Tanner, S. M., Kress, W., Schneider, V., Wallgren-Pettersson, C., Herger, F., Buj-Bello, A., Blondeau, F., Liechti-Gallati, S., Mandel, J.-L.
|
|
<strong>MTM1 mutations in X-linked myotubular myopathy.</strong>
|
|
Hum. Mutat. 15: 393-409, 2000.
|
|
|
|
|
|
[PubMed: 10790201]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<393::AID-HUMU1>3.0.CO;2-R]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laporte, J., Blondeau, F., Buj-Bello, A., Mandel, J.-L.
|
|
<strong>The myotubularin family: from genetic disease to phosphoinositide metabolism.</strong>
|
|
Trends Genet. 17: 221-228, 2001.
|
|
|
|
|
|
[PubMed: 11275328]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0168-9525(01)02245-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laporte, J., Blondeau, F., Buj-Bello, A., Tentler, D., Kretz, C., Dahl, N., Mandel, J.-L.
|
|
<strong>Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human.</strong>
|
|
Hum. Molec. Genet. 7: 1703-1712, 1998.
|
|
|
|
|
|
[PubMed: 9736772]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.11.1703]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laporte, J., Guiraud-Chaumeil, C., Tanner, S. M., Blondeau, F., Hu, L.-J., Vicaire, S., Liechti-Gallati, S., Mandel, J.-L.
|
|
<strong>Genomic organization of the MTM1 gene implicated in X-linked myotubular myopathy.</strong>
|
|
Europ. J. Hum. Genet. 6: 325-330, 1998.
|
|
|
|
|
|
[PubMed: 9781038]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200189]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laporte, J., Guiraud-Chaumeil, C., Vincent, M.-C., Mandel, J.-L., Tanner, S. M., Liechti-Gallati, S., Wallgren-Pettersson, C., Dahl, N., Kress, W., Bolhuis, P. A., Fardeau, M., Samson, F., Bertini, E., members of the ENMC International Consortium on Myotubular Myopathy.
|
|
<strong>Mutations in the MTM1 gene implicated in X-linked myotubular myopathy.</strong>
|
|
Hum. Molec. Genet. 6: 1505-1511, 1997.
|
|
|
|
|
|
[PubMed: 9305655]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/6.9.1505]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Laporte, J., Hu, L. J., Kretz, C., Mandel, J.-L., Kioschis, P., Coy, J. F., Klauck, S. M., Poustka, A., Dahl, N.
|
|
<strong>A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.</strong>
|
|
Nature Genet. 13: 175-182, 1996.
|
|
|
|
|
|
[PubMed: 8640223]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0696-175]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nandurkar, H. H., Layton, M., Laporte, J., Selan, C., Corcoran, L., Caldwell, K. K., Mochizuki, Y., Majerus, P. W., Mitchell, C. A.
|
|
<strong>Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter (sic) protein, 3-PAP.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 8660-8665, 2003.
|
|
|
|
|
|
[PubMed: 12847286]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1033097100]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Samson, F., Mesnard, L., Heimburger, M., Hanauer, A., Chevallay, M., Mercadier, J. J., Pelissier, J. F., Feingold, N., Junien, C., Mandel, J.-L., Fardeau, M.
|
|
<strong>Genetic linkage heterogeneity in myotubular myopathy.</strong>
|
|
Am. J. Hum. Genet. 57: 120-126, 1995.
|
|
|
|
|
|
[PubMed: 7611280]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schara, U., Kress, W., Tucke, J., Mortier, W.
|
|
<strong>X-linked myotubular myopathy in a female infant caused by a new MTM1 gene mutation.</strong>
|
|
Neurology 60: 1363-1365, 2003.
|
|
|
|
|
|
[PubMed: 12707446]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000058763.90924.fa]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sutton, I. J., Winer, J. B., Norman, A. N., Liechti-Gallati, S., MacDonald, F.
|
|
<strong>Limb girdle and facial weakness in female carriers of X-linked myotubular myopathy mutations.</strong>
|
|
Neurology 57: 900-902, 2001.
|
|
|
|
|
|
[PubMed: 11552027]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.57.5.900]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tanner, S. M., Laporte, J., Guiraud-Chaumeil, C., Liechti-Gallati, S.
|
|
<strong>Confirmation of prenatal diagnosis results of X-linked recessive myotubular myopathy by mutational screening, and description of three new mutations in the MTM1 gene.</strong>
|
|
Hum. Mutat. 11: 62-68, 1998.
|
|
|
|
|
|
[PubMed: 9450905]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:1<62::AID-HUMU10>3.0.CO;2-X]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, G. S., Maehama, T., Dixon, J. E.
|
|
<strong>Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 8910-8915, 2000.
|
|
|
|
|
|
[PubMed: 10900271]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.160255697]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsai, T.-C., Horinouchi, H., Noguchi, S., Minami, N., Murayama, K., Hayashi, Y. K., Nonaka, I., Nishino, I.
|
|
<strong>Characterization of MTM1 mutations in 31 Japanese families with myotubular myopathy, including a patient carrying 240 kb deletion in Xq28 without male hypogenitalism.</strong>
|
|
Neuromusc. Disord. 15: 245-252, 2005.
|
|
|
|
|
|
[PubMed: 15725586]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2004.12.005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Wijngaarden, G. K., Fleury, P., Bethlem, J., Meijer, A. E. F. H.
|
|
<strong>Familial 'myotubular' myopathy.</strong>
|
|
Neurology 19: 901-908, 1969.
|
|
|
|
|
|
[PubMed: 5816884]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.19.9.901]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yu, S., Manson, J., White, S., Bourne, A., Waddy, H., Davis, M., Haan, E.
|
|
<strong>X-linked myotubular myopathy in a family with three adult survivors.</strong>
|
|
Clin. Genet. 64: 148-152, 2003.
|
|
|
|
|
|
[PubMed: 12859411]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00118.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
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|
|
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|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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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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Ada Hamosh - updated : 12/14/2016<br>Cassandra L. Kniffin - updated : 12/15/2014<br>Patricia A. Hartz - updated : 10/31/2013<br>Cassandra L. Kniffin - updated : 6/5/2009<br>Cassandra L. Kniffin - updated : 4/11/2005<br>Victor A. McKusick - updated : 8/28/2003<br>Victor A. McKusick - updated : 8/20/2003<br>Cassandra L. Kniffin - updated : 6/16/2003<br>Victor A. McKusick - updated : 1/14/2003
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Creation Date:
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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 : 12/11/2002
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mgross : 05/14/2021<br>alopez : 12/14/2016<br>alopez : 12/22/2014<br>alopez : 12/16/2014<br>mcolton : 12/15/2014<br>ckniffin : 12/15/2014<br>mgross : 11/7/2013<br>mcolton : 11/1/2013<br>mcolton : 10/31/2013<br>carol : 9/1/2010<br>wwang : 6/23/2009<br>wwang : 6/22/2009<br>ckniffin : 6/5/2009<br>wwang : 4/25/2005<br>ckniffin : 4/11/2005<br>cwells : 9/3/2003<br>terry : 8/28/2003<br>tkritzer : 8/27/2003<br>tkritzer : 8/25/2003<br>terry : 8/20/2003<br>carol : 6/16/2003<br>ckniffin : 6/11/2003<br>carol : 1/23/2003<br>carol : 1/23/2003<br>tkritzer : 1/17/2003<br>terry : 1/14/2003<br>carol : 12/17/2002<br>ckniffin : 12/12/2002
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