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Entry
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- *137960 - MITOCHONDRIAL INNER MEMBRANE PROTEIN MPV17; MPV17
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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">*137960</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="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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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/137960">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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</ul>
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</nav>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div 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=ENSG00000115204;t=ENST00000380044" 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=4358" 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=137960" 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=ENSG00000115204;t=ENST00000380044" 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_002437,XM_005264326,XM_017004151" 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_002437" 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=137960" 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=08847&isoform_id=08847_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/MPV17" 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/434977,730059,3252878,4261714,4505241,12654561,34783266,51998557,62988911,119621002,119621003,119621004,119621005,119621006,119621007,119621008,119621009,311349378,311349380,311349382,311349384,311349386,311349388,311349390,311349392,311349394,311349396,311349398,311349400,311349402,311349404,311349406,311349408,311349410,311349412,311349414,311349416,311349418,311349420,311349422,311349424,311349426,311349428,311349430,311349432,311349434,311349436,311349438,311349440,311349442,311349444,311349446,311349448,311349450,311349452,311349454,311349456,530367611,957949786,957949789,957949792,957949795,1034614105,2462573410,2462573412" 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/P39210" 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=4358" 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=ENSG00000115204;t=ENST00000380044" 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=MPV17" 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=MPV17" 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+4358" 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/MPV17" 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:4358" 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/4358" 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=chr2&hgg_gene=ENST00000380044.6&hgg_start=27309492&hgg_end=27323097&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/genes/HGNC:7224" 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/mpv17" 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=137960[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=137960[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/MPV17/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/ENSG00000115204" 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=MPV17" 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=MPV17" 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=MPV17" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=MPV17&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/PA30929" 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:7224" 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/FBgn0039930.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:97138" 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/MPV17#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:97138" 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/4358/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://www.orthodb.org/?ncbi=4358" 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=WBGene00011826;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1168" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4358" 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=MPV17&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> 784346006<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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137960
|
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</span>
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</span>
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</div>
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</div>
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<div>
|
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
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MITOCHONDRIAL INNER MEMBRANE PROTEIN MPV17; MPV17
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</span>
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</h3>
|
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MPV17, MOUSE, HOMOLOG OF
|
|
</span>
|
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</h4>
|
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</div>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MPV17" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MPV17</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>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/2/131?start=-3&limit=10&highlight=131">2p23.3</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:27309492-27323097&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'})">2:27,309,492-27,323,097</a> </span>
|
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</em>
|
|
</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 />
|
|
</div>
|
|
<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">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=618400,256810" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/131?start=-3&limit=10&highlight=131">
|
|
2p23.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, axonal, type 2EE
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/618400"> 618400 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)
|
|
|
|
</span>
|
|
</td>
|
|
<td>
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<p>The MPV17 gene encodes a mitochondrial inner membrane protein that is involved in mitochondrial deoxynucleotide homeostasis and maintenance of mtDNA (summary by <a href="#2" class="mim-tip-reference" title="Baumann, M., Schreiber, H., Schlotter-Weigel, B., Loscher, W. N., Stucka, R., Karall, D., Strom, T. M., Bauer, P., Krabichler, B., Fauth, C., Glaeser, D., Senderek, J. <strong>MPV17 mutations in juvenile- and adult-onset axonal sensorimotor polyneuropathy.</strong> Clin. Genet. 95: 182-186, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30298599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30298599</a>] [<a href="https://doi.org/10.1111/cge.13462" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30298599">Baumann et al., 2019</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30298599" 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 Mpv17 strain of mice carries a transgenically produced retroviral insert in its genome (<a href="#12" class="mim-tip-reference" title="Weiher, H., Noda, T., Gray, D. A., Sharpe, A. H., Jaenisch, R. <strong>Transgenic mouse model of kidney disease: insertional inactivation of ubiquitously expressed gene leads to nephrotic syndrome.</strong> Cell 62: 425-434, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1696177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1696177</a>] [<a href="https://doi.org/10.1016/0092-8674(90)90008-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1696177">Weiher et al., 1990</a>). The integration prevents the expression of the Mpv17 gene, leading to the development of glomerulosclerosis in mice homozygous for the integration. Physiologically and histologically, the phenotype of the kidney disease resembles human glomerulosclerosis. The mice demonstrate nephrotic syndrome at an early age. <a href="#7" class="mim-tip-reference" title="Karasawa, M., Zwacka, R. M., Reuter, A., Fink, T., Hsieh, C. L., Lichter, P., Francke, U., Weiher, H. <strong>The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization.</strong> Hum. Molec. Genet. 2: 1829-1834, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8281143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8281143</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8281143">Karasawa et al. (1993)</a> isolated cDNA clones representing a single RNA species for the human MPV17 gene. Sequence analysis demonstrated over 90% identity to the mouse Mpv17 gene in the region coding for a protein of 176 amino acids and unknown function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1696177+8281143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., Zeviani, M. <strong>MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.</strong> Nature Genet. 38: 570-575, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582910</a>] [<a href="https://doi.org/10.1038/ng1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16582910">Spinazzola et al. (2006)</a> detected MPV17 transcript in human pancreas, kidney, muscle, liver, lung, placenta, brain and heart. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., Zeviani, M. <strong>MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.</strong> Nature Genet. 38: 570-575, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582910</a>] [<a href="https://doi.org/10.1038/ng1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16582910">Spinazzola et al. (2006)</a> noted that the MPV17 gene has 7 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Karasawa, M., Zwacka, R. M., Reuter, A., Fink, T., Hsieh, C. L., Lichter, P., Francke, U., Weiher, H. <strong>The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization.</strong> Hum. Molec. Genet. 2: 1829-1834, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8281143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8281143</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8281143">Karasawa et al. (1993)</a> used somatic cell hybrid analysis and in situ hybridization to map the MPV17 gene to chromosome 2p23-p21. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8281143" 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 Southern analysis of rodent/mouse somatic cell hybrids, <a href="#7" class="mim-tip-reference" title="Karasawa, M., Zwacka, R. M., Reuter, A., Fink, T., Hsieh, C. L., Lichter, P., Francke, U., Weiher, H. <strong>The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization.</strong> Hum. Molec. Genet. 2: 1829-1834, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8281143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8281143</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8281143">Karasawa et al. (1993)</a> demonstrated that the Mpv17 gene is located on mouse chromosome 5, thus defining a new region of homology between human 2p and mouse 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8281143" 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="#5" class="mim-tip-reference" title="Dallabona, C., Marsano, R. M., Arzuffi, P., Ghezzi, D., Mancini, P., Zeviani, M., Ferrero, I., Donnini, C. <strong>Sym1, the yeast ortholog of the MPV17 human disease protein, is a stress-induced bioenergetic and morphogenetic mitochondrial modulator.</strong> Hum. Molec. Genet. 19: 1098-1107, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20042463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20042463</a>] [<a href="https://doi.org/10.1093/hmg/ddp581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20042463">Dallabona et al. (2010)</a> showed that the gene product of the S. cerevisiae ortholog of MPV17, Sym1, is essential to maintain oxidative phosphorylation (OXPHOS), glycogen storage, mitochondrial morphology, and mitochondrial DNA (mtDNA) stability in stressing conditions such as high temperature and ethanol-dependent growth. The authors identified and characterized multicopy suppressor genes and metabolic suppressor compounds. The authors concluded that (i) metabolic impairment and mtDNA instability occur independently as a consequence of Sym1 ablation; (ii) ablation of Sym1 causes depletion of glycogen storage, possibly due to defective anaplerotic flux of tricarboxylic acid (TCA) cycle intermediates to the cytosol; and (iii) flattening of mitochondrial cristae in Sym1-defective organelles suggests a role for Sym1 in the structural preservation of the inner mitochondrial membrane, which could in turn control mtDNA maintenance and stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20042463" 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="Choi, Y.-R., Hong, Y. B., Jung, S.-C., Lee, J. H., Kim, Y. J., Park, H. J., Lee, J., Koo, H., Lee, J.-S., Jwa, D. H., Jung, N., Woo, S.-Y., Kim, S.-B., Chung, K. W., Choi, B.-O. <strong>A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy.</strong> BMC Neurol. 15: 179, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26437932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26437932</a>] [<a href="https://doi.org/10.1186/s12883-015-0430-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26437932">Choi et al. (2015)</a> found that siRNA-mediated knockdown of the Mpv17 gene in murine motor neurons reduced cell proliferation and viability against reactive oxygen species (ROS) compared to controls. Knockdown also adversely affected mitochondrial integrity, as manifest by decreased OXPHOS levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26437932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Alonzo, J. R., Venkataraman, C., Field, M. S., Stover, P. J. <strong>The mitochondrial inner membrane protein MPV17 prevents uracil accumulation in mitochondrial DNA.</strong> J. Biol. Chem. 293: 20285-20294, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30385507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30385507</a>] [<a href="https://doi.org/10.1074/jbc.RA118.004788" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30385507">Alonzo et al. (2018)</a> found knockdown of MPV17 in HeLa cells resulted in a 30% reduction of mitochondrial FPGS (<a href="/entry/136510">136510</a>) and a 43% reduction of mitochondrial folate levels compared with control cells. Uracil levels in mitochondrial DNA were 3-fold higher in MPV17-knockdown cells compared with control cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30385507" 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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In 3 families with mitochondrial DNA depletion syndrome-6 (MTDPS6; <a href="/entry/256810">256810</a>), manifest with hepatic and cerebral involvement, <a href="#9" class="mim-tip-reference" title="Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., Zeviani, M. <strong>MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.</strong> Nature Genet. 38: 570-575, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582910</a>] [<a href="https://doi.org/10.1038/ng1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16582910">Spinazzola et al. (2006)</a> identified a locus on chromosome 2p23-p21 and prioritized the genes on this locus using a new integrative genomic strategy. One of the top-scoring candidates was the MPV17 gene. They found disease-segregating MPV17 mutations (<a href="#0001">137960.0001</a>-<a href="#0004">137960.0004</a>) in the 3 families and demonstrated that, contrary to the alleged peroxisomal localization of the MPV17 gene product, MPV17 is a mitochondrial inner membrane protein, and its absence or malfunction causes failure of oxidative phosphorylation (OXPHOS) and mtDNA depletion in individuals with the hepatocerebral form of MTDPS and also in Mpv17 -/- mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582910" 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>MTDPS6 is also known as Navajo neurohepatopathy (NNH) because it had been described as a disorder prevalent in the Navajo population of the southwestern United States. Patients with NNH present with liver disease, severe sensory and motor neuropathy, corneal anesthesia and scarring, cerebral leukoencephalopathy, failure to thrive, and recurrent metabolic acidosis with intercurrent illness. The similarity of clinical, pathologic, and biochemical features seen in patients with NNH to those in patients with mtDNA depletion syndrome suggested that abnormal regulation of mtDNA copy number may be the primary defect in NNH. Supporting this suggestion was the finding of mtDNA depletion in liver biopsies from 2 patients with NNH (<a href="#11" class="mim-tip-reference" title="Vu, T. H., Tanji, K., Holve, S. A., Bonilla, E., Sokol, R. J., Snyder, R. D., Fiore, S., Deutsch, G. H., DiMauro, S., De Vivo, D. <strong>Navajo neurohepatopathy: a mitochondrial DNA depletion syndrome?</strong> Hepatology 34: 116-120, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431741</a>] [<a href="https://doi.org/10.1053/jhep.2001.25921" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11431741">Vu et al., 2001</a>). Both historical and demographic data from the Navajo population of a western Navajo reservation strongly suggested a founder effect as the origin of NNH. In this situation, homozygosity mapping is a powerful tool for the identification of the disease-causing gene. <a href="#6" class="mim-tip-reference" title="Karadimas, C. L., Vu, T. H., Holve, S. A., Chronopoulou, P., Quinzii, C., Johnsen, S. D., Kurth, J., Eggers, E., Palenzuela, L., Tanji, K., Bonilla, E., De Vivo, D. C., DiMauro, S., Hitano, M. <strong>Navajo neurohepatopathy is caused by a mutation in the MPV17 gene.</strong> Am. J. Hum. Genet. 79: 544-548, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16909392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16909392</a>] [<a href="https://doi.org/10.1086/506913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16909392">Karadimas et al. (2006)</a> performed homozygosity mapping in 2 families with NNH and found a suggestion of linkage to chromosome 2p24. This locus included the MPV17 gene, which, when mutated, was known to cause the hepatocerebral form of mitochondrial DNA depletion. Sequencing of the MPV17 gene in 6 patients with NNH from 5 families, revealed the homozygous arg50-to-gln mutation (<a href="#0001">137960.0001</a>), which had previously been described in a southern Italian family with hepatocerebral mtDNA depletion syndrome. Identification of a single missense mutation in patients with NNH corroborated the notion that the disease is due to a founder effect and extended the phenotypic spectrum associated with MPV17 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11431741+16909392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Charcot-Marie-Tooth Neuropathy, Type 2EE</em></strong></p><p>
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In a 21-year-old Pakistani man with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; <a href="/entry/618400">618400</a>), <a href="#3" class="mim-tip-reference" title="Blakely, E. L., Butterworth, A., Hadden, R. D. M., Bodi, I., He, L., McFarland, R., Taylor, R. W. <strong>MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle.</strong> Neuromusc. Disord. 22: 587-591, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22508010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22508010</a>] [<a href="https://doi.org/10.1016/j.nmd.2012.03.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22508010">Blakely et al. (2012)</a> identified a homozygous missense mutation in the MPV17 gene (P98L; <a href="#0008">137960.0008</a>). The mutation was found by direct sequencing of the MPV17 gene, but DNA from family members was not available for analysis. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22508010" 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 2 unrelated Korean patients with CMT2EE, <a href="#4" class="mim-tip-reference" title="Choi, Y.-R., Hong, Y. B., Jung, S.-C., Lee, J. H., Kim, Y. J., Park, H. J., Lee, J., Koo, H., Lee, J.-S., Jwa, D. H., Jung, N., Woo, S.-Y., Kim, S.-B., Chung, K. W., Choi, B.-O. <strong>A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy.</strong> BMC Neurol. 15: 179, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26437932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26437932</a>] [<a href="https://doi.org/10.1186/s12883-015-0430-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26437932">Choi et al. (2015)</a> identified a homozygous missense mutation in the MPV17 gene (R41Q; <a href="#0009">137960.0009</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. Transfection of the R41Q mutation into murine motor neurons inhibited cell proliferation, caused reduced of several OXPHOS proteins, and induced mtDNA depletion compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26437932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Baumann, M., Schreiber, H., Schlotter-Weigel, B., Loscher, W. N., Stucka, R., Karall, D., Strom, T. M., Bauer, P., Krabichler, B., Fauth, C., Glaeser, D., Senderek, J. <strong>MPV17 mutations in juvenile- and adult-onset axonal sensorimotor polyneuropathy.</strong> Clin. Genet. 95: 182-186, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30298599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30298599</a>] [<a href="https://doi.org/10.1111/cge.13462" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30298599">Baumann et al. (2019)</a> identified a homozygous R41Q mutation in the MPV17 gene in 2 Bosnian patients with CMT2EE. The mutation was found by Sanger sequencing and segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. Three 3 Iraqi brothers from the religious minority of 'Jesidians' (Yazidis) in Northern Iraq with the disorder were found to have a homozygous splice site mutation in the MPV17 gene (<a href="#0010">137960.0010</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The findings expanded the phenotype associated with biallelic MPV17 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30298599" 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 an Mpv17-knockout mouse model, <a href="#10" class="mim-tip-reference" title="Viscomi, C., Spinazzola, A., Maggioni, M., Fernandez-Vizarra, E., Massa, V., Pagano, C., Vettor, R., Mora, M., Zeviani, M. <strong>Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice.</strong> Hum. Molec. Genet. 18: 12-26, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18818194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18818194</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18818194[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18818194">Viscomi et al. (2009)</a> found severe mtDNA depletion in liver and skeletal muscle, whereas hardly any depletion was detected in brain and kidney. Mouse embryonic fibroblasts only showed mtDNA depletion after several culturing passages or in serum-free medium. In spite of severe mtDNA depletion, only moderate decreases in respiratory chain enzymatic activities and mild cytoarchitectural alterations were observed in Mpv17 -/- livers, but neither cirrhosis nor failure ever occurred. The mtDNA transcription rate was markedly increased in liver, which could contribute to compensation for the severe mtDNA depletion. This phenomenon was associated with specific downregulation of Mterf (<a href="/entry/602318">602318</a>), a negative modulator of mtDNA transcription. The most relevant clinical features involved skin, inner ear, and kidney. The coat of the Mpv17 -/- mice turned gray early in adulthood, and 18-month or older mice developed focal segmental glomerulosclerosis (FSGS) with massive proteinuria. Concomitant degeneration of cochlear sensory epithelia was reported as well. These symptoms were associated with significantly shorter life span. Coincidental with the onset of FSGS, minimal mtDNA was measurable in glomerular tufts. <a href="#10" class="mim-tip-reference" title="Viscomi, C., Spinazzola, A., Maggioni, M., Fernandez-Vizarra, E., Massa, V., Pagano, C., Vettor, R., Mora, M., Zeviani, M. <strong>Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice.</strong> Hum. Molec. Genet. 18: 12-26, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18818194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18818194</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18818194[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18818194">Viscomi et al. (2009)</a> concluded that Mpv17 controls mtDNA copy number by a highly tissue-specific and possibly cytotype-specific mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18818194" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121909721 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909721;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121909721?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121909721" 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=rs121909721" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of a southern Italian family with mitochondrial DNA depletion syndrome-6 (MTDPS6; <a href="/entry/256810">256810</a>), manifest with hepatic and cerebral involvement, <a href="#9" class="mim-tip-reference" title="Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., Zeviani, M. <strong>MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.</strong> Nature Genet. 38: 570-575, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582910</a>] [<a href="https://doi.org/10.1038/ng1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16582910">Spinazzola et al. (2006)</a> found homozygosity for a 149G-A transition in exon 2 of the MPV17 gene, resulting in an arg50-to-gln (R50Q) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582910" 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="Karadimas, C. L., Vu, T. H., Holve, S. A., Chronopoulou, P., Quinzii, C., Johnsen, S. D., Kurth, J., Eggers, E., Palenzuela, L., Tanji, K., Bonilla, E., De Vivo, D. C., DiMauro, S., Hitano, M. <strong>Navajo neurohepatopathy is caused by a mutation in the MPV17 gene.</strong> Am. J. Hum. Genet. 79: 544-548, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16909392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16909392</a>] [<a href="https://doi.org/10.1086/506913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16909392">Karadimas et al. (2006)</a> found the R50Q mutation as the basis of MTDPS6, also called Navajo neurohepatopathy because it was described as a founder disorder in the Navajo population of the southwestern United States. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16909392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of a consanguineous Moroccan family with mtDNA depletion syndrome-6 (MTDPS6; <a href="/entry/256810">256810</a>), manifest with hepatic and cerebral involvement, <a href="#9" class="mim-tip-reference" title="Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., Zeviani, M. <strong>MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.</strong> Nature Genet. 38: 570-575, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582910</a>] [<a href="https://doi.org/10.1038/ng1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16582910">Spinazzola et al. (2006)</a> identified homozygosity for a 498C-A transversion in exon 7 of the MPV17 gene, resulting in an asn166-to-lys (N166K) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121909723 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909723;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121909723?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121909723" 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=rs121909723" 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=RCV000017545 OR RCV000264441 OR RCV003227464 OR RCV003473105 OR RCV005025062" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017545, RCV000264441, RCV003227464, RCV003473105, RCV005025062" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017545...</a>
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<p>In a child with mtDNA depletion syndrome-6 (MTDPS6; <a href="/entry/256810">256810</a>), manifest with hepatic and cerebral involvement, <a href="#9" class="mim-tip-reference" title="Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., Zeviani, M. <strong>MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.</strong> Nature Genet. 38: 570-575, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582910</a>] [<a href="https://doi.org/10.1038/ng1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16582910">Spinazzola et al. (2006)</a> found compound heterozygosity for 2 mutations in the MPV17 gene: a 148C-T transition in exon 2 of the MPV17 gene, resulting in an arg50-to-trp (R50W) substitution, and a 26-bp deletion (116-141del; <a href="#0004">137960.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397507438 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397507438;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=rs397507438" 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=rs397507438" 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=RCV000017546" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017546" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017546</a>
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<p>For discussion of the 26-bp deletion in the MPV17 gene (116-141del) that was found in compound heterozygous state in a patient with mtDNA depletion syndrome-6 (MTDPS6; <a href="/entry/256810">256810</a>) by <a href="#9" class="mim-tip-reference" title="Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., Zeviani, M. <strong>MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.</strong> Nature Genet. 38: 570-575, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582910</a>] [<a href="https://doi.org/10.1038/ng1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16582910">Spinazzola et al. (2006)</a>, see <a href="#0003">137960.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121909724 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909724;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121909724?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121909724" 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=rs121909724" 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=RCV000017547 OR RCV001851891 OR RCV003466862" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017547, RCV001851891, RCV003466862" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017547...</a>
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<p>In 2 sisters, born of consanguineous Iraqi parents, with mitochondrial DNA depletion syndrome-6 (MTDPS6; <a href="/entry/256810">256810</a>), manifest with hepatic and cerebral involvement, <a href="#8" class="mim-tip-reference" title="Spinazzola, A., Santer, R., Akman, O. H., Tsiakas, K., Schaefer, H., Ding, X., Karadimas, C. L., Shanske, S., Ganesh, J., Di Mauro, S., Zeviani, M. <strong>Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.</strong> Arch. Neurol. 65: 1108-1113, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18695062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18695062</a>] [<a href="https://doi.org/10.1001/archneur.65.8.1108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18695062">Spinazzola et al. (2008)</a> identified a homozygous 359G-A transition in exon 5 of the MPV17 gene, resulting in a trp120-to-ter (W120X) substitution. Both died from rapidly progressive liver failure at ages 11 and 5 months, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18695062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909725 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909725;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=rs121909725" 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=rs121909725" 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=RCV000017548" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017548" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017548</a>
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<p>In an infant girl with mitochondrial DNA depletion syndrome-6 (MTDPS6; <a href="/entry/256810">256810</a>), <a href="#8" class="mim-tip-reference" title="Spinazzola, A., Santer, R., Akman, O. H., Tsiakas, K., Schaefer, H., Ding, X., Karadimas, C. L., Shanske, S., Ganesh, J., Di Mauro, S., Zeviani, M. <strong>Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.</strong> Arch. Neurol. 65: 1108-1113, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18695062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18695062</a>] [<a href="https://doi.org/10.1001/archneur.65.8.1108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18695062">Spinazzola et al. (2008)</a> identified compound heterozygosity for 2 mutations in the MPV17 gene: a G-to-T transversion resulting in a gly24-to-trp (G24W) substitution in the first transmembrane domain, and a 1.5-kb deletion encompassing intron 7 and part of exon 8 (<a href="#0007">137960.0007</a>). She died of liver failure at age 9 months after developing neurologic signs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18695062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</strong>
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MPV17, 1.5-KB DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000017549" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017549" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017549</a>
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<p>For discussion of the 1.5-kb deletion in the MPV17 gene that was found in compound heterozygous state in a patient with mitochondrial DNA depletion syndrome-6 (MTDPS6; <a href="/entry/256810">256810</a>) by <a href="#8" class="mim-tip-reference" title="Spinazzola, A., Santer, R., Akman, O. H., Tsiakas, K., Schaefer, H., Ding, X., Karadimas, C. L., Shanske, S., Ganesh, J., Di Mauro, S., Zeviani, M. <strong>Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.</strong> Arch. Neurol. 65: 1108-1113, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18695062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18695062</a>] [<a href="https://doi.org/10.1001/archneur.65.8.1108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18695062">Spinazzola et al. (2008)</a>, see <a href="#0006">137960.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18695062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<strong>.0008 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2EE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs267607258 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607258;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs267607258?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267607258" 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=rs267607258" 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=RCV000031911 OR RCV000198122 OR RCV000312148 OR RCV000768420 OR RCV002504849 OR RCV003478980" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000031911, RCV000198122, RCV000312148, RCV000768420, RCV002504849, RCV003478980" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000031911...</a>
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<p>In a 21-year-old Pakistani man with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; <a href="/entry/618400">618400</a>), <a href="#3" class="mim-tip-reference" title="Blakely, E. L., Butterworth, A., Hadden, R. D. M., Bodi, I., He, L., McFarland, R., Taylor, R. W. <strong>MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle.</strong> Neuromusc. Disord. 22: 587-591, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22508010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22508010</a>] [<a href="https://doi.org/10.1016/j.nmd.2012.03.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22508010">Blakely et al. (2012)</a> identified a homozygous c.2898C-T transition (c.2898C-T, NM_002437.4) in the MPV17 gene, resulting in a pro98-to-leu (P98L) substitution at a highly conserved residue. The mutation was found by direct sequencing of MPV17 and 2 other genes implicated in mitochondrial DNA maintenance disorders with hepatocerebral involvement; DNA from family members was not available for analysis. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22508010" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2EE</strong>
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MPV17, ARG41GLN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs140992482 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs140992482;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs140992482?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs140992482" 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=rs140992482" 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=RCV000768421 OR RCV000792530 OR RCV002279731 OR RCV003226382 OR RCV003227501 OR RCV003476888 OR RCV004733041" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000768421, RCV000792530, RCV002279731, RCV003226382, RCV003227501, RCV003476888, RCV004733041" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000768421...</a>
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<p>In 2 unrelated Korean patients with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; <a href="/entry/618400">618400</a>), <a href="#4" class="mim-tip-reference" title="Choi, Y.-R., Hong, Y. B., Jung, S.-C., Lee, J. H., Kim, Y. J., Park, H. J., Lee, J., Koo, H., Lee, J.-S., Jwa, D. H., Jung, N., Woo, S.-Y., Kim, S.-B., Chung, K. W., Choi, B.-O. <strong>A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy.</strong> BMC Neurol. 15: 179, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26437932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26437932</a>] [<a href="https://doi.org/10.1186/s12883-015-0430-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26437932">Choi et al. (2015)</a> identified a homozygous c.122G-A transition in the MPV17 gene, resulting in an arg41-to-gln (R41Q) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. The mutation was not found in the dbSNP (build 142) or 1000 Genomes Project databases, but was found at a low frequency in the Exome Sequencing Project (0.00008) and ExAC (0.00002471) databases. Transfection of the R41Q mutation into murine motor neurons inhibited cell proliferation, caused reduced of several OXPHOS proteins, and induced mtDNA depletion compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26437932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Baumann, M., Schreiber, H., Schlotter-Weigel, B., Loscher, W. N., Stucka, R., Karall, D., Strom, T. M., Bauer, P., Krabichler, B., Fauth, C., Glaeser, D., Senderek, J. <strong>MPV17 mutations in juvenile- and adult-onset axonal sensorimotor polyneuropathy.</strong> Clin. Genet. 95: 182-186, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30298599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30298599</a>] [<a href="https://doi.org/10.1111/cge.13462" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30298599">Baumann et al. (2019)</a> identified a homozygous R41Q mutation in the MPV17 gene in 2 Bosnian patients with CMT2EE. The mutation was found by Sanger sequencing and segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30298599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2EE</strong>
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MPV17, IVS5AS, T-G, -9
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs368900406 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs368900406;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs368900406?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs368900406" 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=rs368900406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000728355 OR RCV000735227 OR RCV000768422" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000728355, RCV000735227, RCV000768422" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000728355...</a>
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<p>In 3 brothers from the religious minority of 'Jesidians' (Yazidis) in northern Iraq with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; <a href="/entry/618400">618400</a>), <a href="#2" class="mim-tip-reference" title="Baumann, M., Schreiber, H., Schlotter-Weigel, B., Loscher, W. N., Stucka, R., Karall, D., Strom, T. M., Bauer, P., Krabichler, B., Fauth, C., Glaeser, D., Senderek, J. <strong>MPV17 mutations in juvenile- and adult-onset axonal sensorimotor polyneuropathy.</strong> Clin. Genet. 95: 182-186, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30298599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30298599</a>] [<a href="https://doi.org/10.1111/cge.13462" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30298599">Baumann et al. (2019)</a> identified a homozygous T-to-G transversion in intron 5 of the MPV17 gene (c.376-9T-G), resulting in a splicing defect. RT-PCR analysis of patient cells showed that the mutation resulted in skipping of exon 6 in the majority of mRNAs, causing an in-frame deletion of 11 residues (Asp126_Tyr136del). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found at a low frequency in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30298599" 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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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>REFERENCES</strong>
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Alonzo, J. R., Venkataraman, C., Field, M. S., Stover, P. J.
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<strong>The mitochondrial inner membrane protein MPV17 prevents uracil accumulation in mitochondrial DNA.</strong>
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J. Biol. Chem. 293: 20285-20294, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30385507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30385507</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30385507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.RA118.004788" target="_blank">Full Text</a>]
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Baumann, M., Schreiber, H., Schlotter-Weigel, B., Loscher, W. N., Stucka, R., Karall, D., Strom, T. M., Bauer, P., Krabichler, B., Fauth, C., Glaeser, D., Senderek, J.
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<strong>MPV17 mutations in juvenile- and adult-onset axonal sensorimotor polyneuropathy.</strong>
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Clin. Genet. 95: 182-186, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30298599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30298599</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30298599" 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/10.1111/cge.13462" target="_blank">Full Text</a>]
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<a id="Blakely2012" class="mim-anchor"></a>
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Blakely, E. L., Butterworth, A., Hadden, R. D. M., Bodi, I., He, L., McFarland, R., Taylor, R. W.
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<strong>MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle.</strong>
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Neuromusc. Disord. 22: 587-591, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22508010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22508010</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22508010" 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.2012.03.006" target="_blank">Full Text</a>]
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<a id="Choi2015" class="mim-anchor"></a>
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Choi, Y.-R., Hong, Y. B., Jung, S.-C., Lee, J. H., Kim, Y. J., Park, H. J., Lee, J., Koo, H., Lee, J.-S., Jwa, D. H., Jung, N., Woo, S.-Y., Kim, S.-B., Chung, K. W., Choi, B.-O.
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<strong>A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy.</strong>
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BMC Neurol. 15: 179, 2015. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26437932/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26437932</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26437932" 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/10.1186/s12883-015-0430-1" target="_blank">Full Text</a>]
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<a id="Dallabona2010" class="mim-anchor"></a>
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Dallabona, C., Marsano, R. M., Arzuffi, P., Ghezzi, D., Mancini, P., Zeviani, M., Ferrero, I., Donnini, C.
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<strong>Sym1, the yeast ortholog of the MPV17 human disease protein, is a stress-induced bioenergetic and morphogenetic mitochondrial modulator.</strong>
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Hum. Molec. Genet. 19: 1098-1107, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20042463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20042463</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20042463" 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/ddp581" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Karadimas2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Karadimas, C. L., Vu, T. H., Holve, S. A., Chronopoulou, P., Quinzii, C., Johnsen, S. D., Kurth, J., Eggers, E., Palenzuela, L., Tanji, K., Bonilla, E., De Vivo, D. C., DiMauro, S., Hitano, M.
|
|
<strong>Navajo neurohepatopathy is caused by a mutation in the MPV17 gene.</strong>
|
|
Am. J. Hum. Genet. 79: 544-548, 2006.
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|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16909392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16909392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16909392" 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/10.1086/506913" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Karasawa1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Karasawa, M., Zwacka, R. M., Reuter, A., Fink, T., Hsieh, C. L., Lichter, P., Francke, U., Weiher, H.
|
|
<strong>The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization.</strong>
|
|
Hum. Molec. Genet. 2: 1829-1834, 1993.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8281143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8281143</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8281143" 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/2.11.1829" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Spinazzola2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Spinazzola, A., Santer, R., Akman, O. H., Tsiakas, K., Schaefer, H., Ding, X., Karadimas, C. L., Shanske, S., Ganesh, J., Di Mauro, S., Zeviani, M.
|
|
<strong>Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.</strong>
|
|
Arch. Neurol. 65: 1108-1113, 2008.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18695062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18695062</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18695062" 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/10.1001/archneur.65.8.1108" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Spinazzola2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., Zeviani, M.
|
|
<strong>MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.</strong>
|
|
Nature Genet. 38: 570-575, 2006.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582910</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1765" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Viscomi2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Viscomi, C., Spinazzola, A., Maggioni, M., Fernandez-Vizarra, E., Massa, V., Pagano, C., Vettor, R., Mora, M., Zeviani, M.
|
|
<strong>Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice.</strong>
|
|
Hum. Molec. Genet. 18: 12-26, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18818194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18818194</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18818194[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=18818194" 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/ddn309" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Vu2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vu, T. H., Tanji, K., Holve, S. A., Bonilla, E., Sokol, R. J., Snyder, R. D., Fiore, S., Deutsch, G. H., DiMauro, S., De Vivo, D.
|
|
<strong>Navajo neurohepatopathy: a mitochondrial DNA depletion syndrome?</strong>
|
|
Hepatology 34: 116-120, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431741</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11431741" 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/10.1053/jhep.2001.25921" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Weiher1990" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weiher, H., Noda, T., Gray, D. A., Sharpe, A. H., Jaenisch, R.
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<strong>Transgenic mouse model of kidney disease: insertional inactivation of ubiquitously expressed gene leads to nephrotic syndrome.</strong>
|
|
Cell 62: 425-434, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1696177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1696177</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1696177" 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/10.1016/0092-8674(90)90008-3" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 05/10/2019
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 04/24/2019<br>George E. Tiller - updated : 11/10/2011<br>George E. Tiller - updated : 10/23/2009<br>Cassandra L. Kniffin - updated : 10/16/2008<br>Victor A. McKusick - updated : 8/23/2006<br>Victor A. McKusick - updated : 4/26/2006
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 12/10/1993
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/03/2019
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/16/2019<br>mgross : 05/10/2019<br>carol : 04/29/2019<br>alopez : 04/25/2019<br>ckniffin : 04/24/2019<br>carol : 08/12/2016<br>mcolton : 06/26/2015<br>alopez : 11/17/2011<br>terry : 11/10/2011<br>carol : 12/21/2010<br>ckniffin : 12/9/2010<br>wwang : 11/2/2009<br>terry : 10/23/2009<br>wwang : 10/20/2008<br>ckniffin : 10/16/2008<br>alopez : 8/25/2006<br>terry : 8/23/2006<br>wwang : 5/2/2006<br>terry : 4/26/2006<br>dkim : 12/15/1998<br>carol : 4/21/1994<br>carol : 12/10/1993
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 137960
|
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</span>
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</h3>
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</div>
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<div>
|
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<h3>
|
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<span class="mim-font">
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MITOCHONDRIAL INNER MEMBRANE PROTEIN MPV17; MPV17
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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MPV17, MOUSE, HOMOLOG OF
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: MPV17</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 784346006;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: 2p23.3
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|
|
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:27,309,492-27,323,097 </span>
|
|
</em>
|
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</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
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<tr class="active">
|
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<th>
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Location
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</th>
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<th>
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Phenotype
|
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</th>
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<th>
|
|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
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|
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<tr>
|
|
<td rowspan="2">
|
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<span class="mim-font">
|
|
2p23.3
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, axonal, type 2EE
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
618400
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
|
<span class="mim-font">
|
|
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)
|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
256810
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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</tbody>
|
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>The MPV17 gene encodes a mitochondrial inner membrane protein that is involved in mitochondrial deoxynucleotide homeostasis and maintenance of mtDNA (summary by Baumann et al., 2019). </p>
|
|
</span>
|
|
<div>
|
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<br />
|
|
</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The Mpv17 strain of mice carries a transgenically produced retroviral insert in its genome (Weiher et al., 1990). The integration prevents the expression of the Mpv17 gene, leading to the development of glomerulosclerosis in mice homozygous for the integration. Physiologically and histologically, the phenotype of the kidney disease resembles human glomerulosclerosis. The mice demonstrate nephrotic syndrome at an early age. Karasawa et al. (1993) isolated cDNA clones representing a single RNA species for the human MPV17 gene. Sequence analysis demonstrated over 90% identity to the mouse Mpv17 gene in the region coding for a protein of 176 amino acids and unknown function. </p><p>Spinazzola et al. (2006) detected MPV17 transcript in human pancreas, kidney, muscle, liver, lung, placenta, brain and heart. </p>
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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>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Spinazzola et al. (2006) noted that the MPV17 gene has 7 exons. </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>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Karasawa et al. (1993) used somatic cell hybrid analysis and in situ hybridization to map the MPV17 gene to chromosome 2p23-p21. </p><p>By Southern analysis of rodent/mouse somatic cell hybrids, Karasawa et al. (1993) demonstrated that the Mpv17 gene is located on mouse chromosome 5, thus defining a new region of homology between human 2p and mouse 5. </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>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Dallabona et al. (2010) showed that the gene product of the S. cerevisiae ortholog of MPV17, Sym1, is essential to maintain oxidative phosphorylation (OXPHOS), glycogen storage, mitochondrial morphology, and mitochondrial DNA (mtDNA) stability in stressing conditions such as high temperature and ethanol-dependent growth. The authors identified and characterized multicopy suppressor genes and metabolic suppressor compounds. The authors concluded that (i) metabolic impairment and mtDNA instability occur independently as a consequence of Sym1 ablation; (ii) ablation of Sym1 causes depletion of glycogen storage, possibly due to defective anaplerotic flux of tricarboxylic acid (TCA) cycle intermediates to the cytosol; and (iii) flattening of mitochondrial cristae in Sym1-defective organelles suggests a role for Sym1 in the structural preservation of the inner mitochondrial membrane, which could in turn control mtDNA maintenance and stability. </p><p>Choi et al. (2015) found that siRNA-mediated knockdown of the Mpv17 gene in murine motor neurons reduced cell proliferation and viability against reactive oxygen species (ROS) compared to controls. Knockdown also adversely affected mitochondrial integrity, as manifest by decreased OXPHOS levels. </p><p>Alonzo et al. (2018) found knockdown of MPV17 in HeLa cells resulted in a 30% reduction of mitochondrial FPGS (136510) and a 43% reduction of mitochondrial folate levels compared with control cells. Uracil levels in mitochondrial DNA were 3-fold higher in MPV17-knockdown cells compared with control cells. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Mitochondrial DNA Depletion Syndrome 6</em></strong></p><p>
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In 3 families with mitochondrial DNA depletion syndrome-6 (MTDPS6; 256810), manifest with hepatic and cerebral involvement, Spinazzola et al. (2006) identified a locus on chromosome 2p23-p21 and prioritized the genes on this locus using a new integrative genomic strategy. One of the top-scoring candidates was the MPV17 gene. They found disease-segregating MPV17 mutations (137960.0001-137960.0004) in the 3 families and demonstrated that, contrary to the alleged peroxisomal localization of the MPV17 gene product, MPV17 is a mitochondrial inner membrane protein, and its absence or malfunction causes failure of oxidative phosphorylation (OXPHOS) and mtDNA depletion in individuals with the hepatocerebral form of MTDPS and also in Mpv17 -/- mice. </p><p>MTDPS6 is also known as Navajo neurohepatopathy (NNH) because it had been described as a disorder prevalent in the Navajo population of the southwestern United States. Patients with NNH present with liver disease, severe sensory and motor neuropathy, corneal anesthesia and scarring, cerebral leukoencephalopathy, failure to thrive, and recurrent metabolic acidosis with intercurrent illness. The similarity of clinical, pathologic, and biochemical features seen in patients with NNH to those in patients with mtDNA depletion syndrome suggested that abnormal regulation of mtDNA copy number may be the primary defect in NNH. Supporting this suggestion was the finding of mtDNA depletion in liver biopsies from 2 patients with NNH (Vu et al., 2001). Both historical and demographic data from the Navajo population of a western Navajo reservation strongly suggested a founder effect as the origin of NNH. In this situation, homozygosity mapping is a powerful tool for the identification of the disease-causing gene. Karadimas et al. (2006) performed homozygosity mapping in 2 families with NNH and found a suggestion of linkage to chromosome 2p24. This locus included the MPV17 gene, which, when mutated, was known to cause the hepatocerebral form of mitochondrial DNA depletion. Sequencing of the MPV17 gene in 6 patients with NNH from 5 families, revealed the homozygous arg50-to-gln mutation (137960.0001), which had previously been described in a southern Italian family with hepatocerebral mtDNA depletion syndrome. Identification of a single missense mutation in patients with NNH corroborated the notion that the disease is due to a founder effect and extended the phenotypic spectrum associated with MPV17 mutations. </p><p><strong><em>Charcot-Marie-Tooth Neuropathy, Type 2EE</em></strong></p><p>
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|
In a 21-year-old Pakistani man with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; 618400), Blakely et al. (2012) identified a homozygous missense mutation in the MPV17 gene (P98L; 137960.0008). The mutation was found by direct sequencing of the MPV17 gene, but DNA from family members was not available for analysis. Functional studies of the variant were not performed. </p><p>In 2 unrelated Korean patients with CMT2EE, Choi et al. (2015) identified a homozygous missense mutation in the MPV17 gene (R41Q; 137960.0009). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. Transfection of the R41Q mutation into murine motor neurons inhibited cell proliferation, caused reduced of several OXPHOS proteins, and induced mtDNA depletion compared to controls. </p><p>Baumann et al. (2019) identified a homozygous R41Q mutation in the MPV17 gene in 2 Bosnian patients with CMT2EE. The mutation was found by Sanger sequencing and segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. Three 3 Iraqi brothers from the religious minority of 'Jesidians' (Yazidis) in Northern Iraq with the disorder were found to have a homozygous splice site mutation in the MPV17 gene (137960.0010). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The findings expanded the phenotype associated with biallelic MPV17 mutations. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In an Mpv17-knockout mouse model, Viscomi et al. (2009) found severe mtDNA depletion in liver and skeletal muscle, whereas hardly any depletion was detected in brain and kidney. Mouse embryonic fibroblasts only showed mtDNA depletion after several culturing passages or in serum-free medium. In spite of severe mtDNA depletion, only moderate decreases in respiratory chain enzymatic activities and mild cytoarchitectural alterations were observed in Mpv17 -/- livers, but neither cirrhosis nor failure ever occurred. The mtDNA transcription rate was markedly increased in liver, which could contribute to compensation for the severe mtDNA depletion. This phenomenon was associated with specific downregulation of Mterf (602318), a negative modulator of mtDNA transcription. The most relevant clinical features involved skin, inner ear, and kidney. The coat of the Mpv17 -/- mice turned gray early in adulthood, and 18-month or older mice developed focal segmental glomerulosclerosis (FSGS) with massive proteinuria. Concomitant degeneration of cochlear sensory epithelia was reported as well. These symptoms were associated with significantly shorter life span. Coincidental with the onset of FSGS, minimal mtDNA was measurable in glomerular tufts. Viscomi et al. (2009) concluded that Mpv17 controls mtDNA copy number by a highly tissue-specific and possibly cytotype-specific mechanism. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>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">
|
|
<strong>.0001 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</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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MPV17, ARG50GLN
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<br />
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SNP: rs121909721,
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gnomAD: rs121909721,
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ClinVar: RCV000017543, RCV000712314, RCV002509162, RCV003466861, RCV004732550, RCV004786268
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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 affected members of a southern Italian family with mitochondrial DNA depletion syndrome-6 (MTDPS6; 256810), manifest with hepatic and cerebral involvement, Spinazzola et al. (2006) found homozygosity for a 149G-A transition in exon 2 of the MPV17 gene, resulting in an arg50-to-gln (R50Q) substitution. </p><p>Karadimas et al. (2006) found the R50Q mutation as the basis of MTDPS6, also called Navajo neurohepatopathy because it was described as a founder disorder in the Navajo population of the southwestern United States. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0002 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</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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MPV17, ASN166LYS
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<br />
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SNP: rs121909722,
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ClinVar: RCV000017544
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In affected members of a consanguineous Moroccan family with mtDNA depletion syndrome-6 (MTDPS6; 256810), manifest with hepatic and cerebral involvement, Spinazzola et al. (2006) identified homozygosity for a 498C-A transversion in exon 7 of the MPV17 gene, resulting in an asn166-to-lys (N166K) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0003 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</strong>
|
|
</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MPV17, ARG50TRP
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<br />
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SNP: rs121909723,
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gnomAD: rs121909723,
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ClinVar: RCV000017545, RCV000264441, RCV003227464, RCV003473105, RCV005025062
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a child with mtDNA depletion syndrome-6 (MTDPS6; 256810), manifest with hepatic and cerebral involvement, Spinazzola et al. (2006) found compound heterozygosity for 2 mutations in the MPV17 gene: a 148C-T transition in exon 2 of the MPV17 gene, resulting in an arg50-to-trp (R50W) substitution, and a 26-bp deletion (116-141del; 137960.0004). </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</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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MPV17, 26-BP DEL, NT116
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<br />
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SNP: rs397507438,
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ClinVar: RCV000017546
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 26-bp deletion in the MPV17 gene (116-141del) that was found in compound heterozygous state in a patient with mtDNA depletion syndrome-6 (MTDPS6; 256810) by Spinazzola et al. (2006), see 137960.0003. </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>.0005 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
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MPV17, TRP120TER
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<br />
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|
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SNP: rs121909724,
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gnomAD: rs121909724,
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|
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ClinVar: RCV000017547, RCV001851891, RCV003466862
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|
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|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sisters, born of consanguineous Iraqi parents, with mitochondrial DNA depletion syndrome-6 (MTDPS6; 256810), manifest with hepatic and cerebral involvement, Spinazzola et al. (2008) identified a homozygous 359G-A transition in exon 5 of the MPV17 gene, resulting in a trp120-to-ter (W120X) substitution. Both died from rapidly progressive liver failure at ages 11 and 5 months, respectively. </p>
|
|
</span>
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</div>
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<div>
|
|
<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 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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MPV17, GLY24TRP
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<br />
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|
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SNP: rs121909725,
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ClinVar: RCV000017548
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant girl with mitochondrial DNA depletion syndrome-6 (MTDPS6; 256810), Spinazzola et al. (2008) identified compound heterozygosity for 2 mutations in the MPV17 gene: a G-to-T transversion resulting in a gly24-to-trp (G24W) substitution in the first transmembrane domain, and a 1.5-kb deletion encompassing intron 7 and part of exon 8 (137960.0007). She died of liver failure at age 9 months after developing neurologic signs. </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>.0007 MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE)</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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|
MPV17, 1.5-KB DEL
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<br />
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|
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ClinVar: RCV000017549
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1.5-kb deletion in the MPV17 gene that was found in compound heterozygous state in a patient with mitochondrial DNA depletion syndrome-6 (MTDPS6; 256810) by Spinazzola et al. (2008), see 137960.0006. </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>.0008 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2EE</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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MPV17, PRO98LEU
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<br />
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|
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SNP: rs267607258,
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gnomAD: rs267607258,
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ClinVar: RCV000031911, RCV000198122, RCV000312148, RCV000768420, RCV002504849, RCV003478980
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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 21-year-old Pakistani man with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; 618400), Blakely et al. (2012) identified a homozygous c.2898C-T transition (c.2898C-T, NM_002437.4) in the MPV17 gene, resulting in a pro98-to-leu (P98L) substitution at a highly conserved residue. The mutation was found by direct sequencing of MPV17 and 2 other genes implicated in mitochondrial DNA maintenance disorders with hepatocerebral involvement; DNA from family members was not available for analysis. Functional studies of the variant were not performed. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<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 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2EE</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<span class="mim-text-font">
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MPV17, ARG41GLN
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<br />
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SNP: rs140992482,
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gnomAD: rs140992482,
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ClinVar: RCV000768421, RCV000792530, RCV002279731, RCV003226382, RCV003227501, RCV003476888, RCV004733041
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</span>
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<p>In 2 unrelated Korean patients with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; 618400), Choi et al. (2015) identified a homozygous c.122G-A transition in the MPV17 gene, resulting in an arg41-to-gln (R41Q) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. The mutation was not found in the dbSNP (build 142) or 1000 Genomes Project databases, but was found at a low frequency in the Exome Sequencing Project (0.00008) and ExAC (0.00002471) databases. Transfection of the R41Q mutation into murine motor neurons inhibited cell proliferation, caused reduced of several OXPHOS proteins, and induced mtDNA depletion compared to controls. </p><p>Baumann et al. (2019) identified a homozygous R41Q mutation in the MPV17 gene in 2 Bosnian patients with CMT2EE. The mutation was found by Sanger sequencing and segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. </p>
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<h4>
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<span class="mim-font">
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<strong>.0010 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2EE</strong>
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</h4>
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<span class="mim-text-font">
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MPV17, IVS5AS, T-G, -9
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<br />
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SNP: rs368900406,
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gnomAD: rs368900406,
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ClinVar: RCV000728355, RCV000735227, RCV000768422
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<span class="mim-text-font">
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<p>In 3 brothers from the religious minority of 'Jesidians' (Yazidis) in northern Iraq with autosomal recessive Charcot-Marie-Tooth neuropathy type 2EE (CMT2EE; 618400), Baumann et al. (2019) identified a homozygous T-to-G transversion in intron 5 of the MPV17 gene (c.376-9T-G), resulting in a splicing defect. RT-PCR analysis of patient cells showed that the mutation resulted in skipping of exon 6 in the majority of mRNAs, causing an in-frame deletion of 11 residues (Asp126_Tyr136del). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found at a low frequency in the gnomAD database. </p>
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</span>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</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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<ol>
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<li>
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<p class="mim-text-font">
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Alonzo, J. R., Venkataraman, C., Field, M. S., Stover, P. J.
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<strong>The mitochondrial inner membrane protein MPV17 prevents uracil accumulation in mitochondrial DNA.</strong>
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J. Biol. Chem. 293: 20285-20294, 2018.
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[PubMed: 30385507]
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[Full Text: https://doi.org/10.1074/jbc.RA118.004788]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Baumann, M., Schreiber, H., Schlotter-Weigel, B., Loscher, W. N., Stucka, R., Karall, D., Strom, T. M., Bauer, P., Krabichler, B., Fauth, C., Glaeser, D., Senderek, J.
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<strong>MPV17 mutations in juvenile- and adult-onset axonal sensorimotor polyneuropathy.</strong>
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Clin. Genet. 95: 182-186, 2019.
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[PubMed: 30298599]
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[Full Text: https://doi.org/10.1111/cge.13462]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Blakely, E. L., Butterworth, A., Hadden, R. D. M., Bodi, I., He, L., McFarland, R., Taylor, R. W.
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<strong>MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle.</strong>
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Neuromusc. Disord. 22: 587-591, 2012.
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[PubMed: 22508010]
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[Full Text: https://doi.org/10.1016/j.nmd.2012.03.006]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Choi, Y.-R., Hong, Y. B., Jung, S.-C., Lee, J. H., Kim, Y. J., Park, H. J., Lee, J., Koo, H., Lee, J.-S., Jwa, D. H., Jung, N., Woo, S.-Y., Kim, S.-B., Chung, K. W., Choi, B.-O.
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<strong>A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy.</strong>
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BMC Neurol. 15: 179, 2015. Note: Electronic Article.
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[PubMed: 26437932]
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[Full Text: https://doi.org/10.1186/s12883-015-0430-1]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dallabona, C., Marsano, R. M., Arzuffi, P., Ghezzi, D., Mancini, P., Zeviani, M., Ferrero, I., Donnini, C.
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<strong>Sym1, the yeast ortholog of the MPV17 human disease protein, is a stress-induced bioenergetic and morphogenetic mitochondrial modulator.</strong>
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Hum. Molec. Genet. 19: 1098-1107, 2010.
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[PubMed: 20042463]
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[Full Text: https://doi.org/10.1093/hmg/ddp581]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Karadimas, C. L., Vu, T. H., Holve, S. A., Chronopoulou, P., Quinzii, C., Johnsen, S. D., Kurth, J., Eggers, E., Palenzuela, L., Tanji, K., Bonilla, E., De Vivo, D. C., DiMauro, S., Hitano, M.
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<strong>Navajo neurohepatopathy is caused by a mutation in the MPV17 gene.</strong>
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Am. J. Hum. Genet. 79: 544-548, 2006.
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[PubMed: 16909392]
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[Full Text: https://doi.org/10.1086/506913]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Karasawa, M., Zwacka, R. M., Reuter, A., Fink, T., Hsieh, C. L., Lichter, P., Francke, U., Weiher, H.
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<strong>The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization.</strong>
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Hum. Molec. Genet. 2: 1829-1834, 1993.
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[PubMed: 8281143]
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[Full Text: https://doi.org/10.1093/hmg/2.11.1829]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Spinazzola, A., Santer, R., Akman, O. H., Tsiakas, K., Schaefer, H., Ding, X., Karadimas, C. L., Shanske, S., Ganesh, J., Di Mauro, S., Zeviani, M.
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|
<strong>Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.</strong>
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Arch. Neurol. 65: 1108-1113, 2008.
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[PubMed: 18695062]
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[Full Text: https://doi.org/10.1001/archneur.65.8.1108]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., Zeviani, M.
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<strong>MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.</strong>
|
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Nature Genet. 38: 570-575, 2006.
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[PubMed: 16582910]
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[Full Text: https://doi.org/10.1038/ng1765]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Viscomi, C., Spinazzola, A., Maggioni, M., Fernandez-Vizarra, E., Massa, V., Pagano, C., Vettor, R., Mora, M., Zeviani, M.
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<strong>Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice.</strong>
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Hum. Molec. Genet. 18: 12-26, 2009.
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[PubMed: 18818194]
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[Full Text: https://doi.org/10.1093/hmg/ddn309]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Vu, T. H., Tanji, K., Holve, S. A., Bonilla, E., Sokol, R. J., Snyder, R. D., Fiore, S., Deutsch, G. H., DiMauro, S., De Vivo, D.
|
|
<strong>Navajo neurohepatopathy: a mitochondrial DNA depletion syndrome?</strong>
|
|
Hepatology 34: 116-120, 2001.
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[PubMed: 11431741]
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[Full Text: https://doi.org/10.1053/jhep.2001.25921]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Weiher, H., Noda, T., Gray, D. A., Sharpe, A. H., Jaenisch, R.
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<strong>Transgenic mouse model of kidney disease: insertional inactivation of ubiquitously expressed gene leads to nephrotic syndrome.</strong>
|
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Cell 62: 425-434, 1990.
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[PubMed: 1696177]
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[Full Text: https://doi.org/10.1016/0092-8674(90)90008-3]
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</p>
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</li>
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</ol>
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<div>
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<br />
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Contributors:
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<span class="mim-text-font">
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Bao Lige - updated : 05/10/2019<br>Cassandra L. Kniffin - updated : 04/24/2019<br>George E. Tiller - updated : 11/10/2011<br>George E. Tiller - updated : 10/23/2009<br>Cassandra L. Kniffin - updated : 10/16/2008<br>Victor A. McKusick - updated : 8/23/2006<br>Victor A. McKusick - updated : 4/26/2006
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<span class="mim-text-font">
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Victor A. McKusick : 12/10/1993
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carol : 09/03/2019<br>carol : 08/16/2019<br>mgross : 05/10/2019<br>carol : 04/29/2019<br>alopez : 04/25/2019<br>ckniffin : 04/24/2019<br>carol : 08/12/2016<br>mcolton : 06/26/2015<br>alopez : 11/17/2011<br>terry : 11/10/2011<br>carol : 12/21/2010<br>ckniffin : 12/9/2010<br>wwang : 11/2/2009<br>terry : 10/23/2009<br>wwang : 10/20/2008<br>ckniffin : 10/16/2008<br>alopez : 8/25/2006<br>terry : 8/23/2006<br>wwang : 5/2/2006<br>terry : 4/26/2006<br>dkim : 12/15/1998<br>carol : 4/21/1994<br>carol : 12/10/1993
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