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- *516005 - COMPLEX I, SUBUNIT ND5; MTND5
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- OMIM
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<p>
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<span class="h4">*516005</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</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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<a href="#mapping">Mapping</a>
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<a href="#geneStructure">Gene Structure</a>
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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="#geneticVariability">Genetic Variability</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/516005">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<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=ENSG00000198786;t=-" 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://mitomap.org/bin/view.pl/Main/SearchSite?search=MT-ND5" class="mim-tip-hint" title="A curated repository of published and unpublished data on human mitochondrial DNA variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MITOMAP', 'domain': 'mitomap.org'})">MITOMAP</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=4540" 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=516005" 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 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=ENSG00000198786;t=-" 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</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=516005" 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://www.proteinatlas.org/search/MT-ND5" 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/2052366,6648059,251831117" 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/P03915" 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=4540" 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=ENSG00000198786;t=-" 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=MT-ND5" 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=MT-ND5" 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+4540" 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/MT-ND5" 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:4540" 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/4540" 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>
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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:7461" 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/mt-nd5" 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=516005[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 class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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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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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=516005[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/MT-ND5/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/ENSG00000198786" 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.gwascentral.org/search?q=MT-ND5" 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=MT-ND5" 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=MT-ND5&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/PA31265" 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 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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<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:7461" 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/FBgn0013684.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:102496" 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/MT-ND5#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:102496" 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/4540/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=4540" 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 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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<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 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:4540" 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=MT-ND5&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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<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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<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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<a id="title" class="mim-anchor"></a>
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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> 230426003, 39925003, 58610003<br />
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<strong>ICD10CM:</strong> E88.41, E88.42, H47.22<br />
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">ICD+</a>
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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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516005
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</span>
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</span>
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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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COMPLEX I, SUBUNIT ND5; MTND5
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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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<a id="alternativeTitles" class="mim-anchor"></a>
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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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<div>
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<h4>
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<span class="mim-font">
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NADH-UBIQUINONE OXIDOREDUCTASE, SUBUNIT ND5<br />
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NADH DEHYDROGENASE, SUBUNIT 5
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</h4>
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</div>
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<div>
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<br />
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MT-ND5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MT-ND5</a></em></strong>
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<div>
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<br />
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Subunit 5 is 1 of the 7 mitochondrial DNA (mtDNA) encoded subunits (MTND1, MTND2, MTND3, MTND4L, MTND4, MTND5, MTND6) included among the approximately 41 polypeptides of respiratory complex I (NADH:ubiquinone oxidoreductase, <a href="https://enzyme.expasy.org/EC/1.6.5.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.6.5.3</a>)(<a href="#36" class="mim-tip-reference" title="Shoffner, J. M., Wallace, D. C. <strong>Oxidative phosphorylation diseases.In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. Vol. 1.</strong> New York: McGraw-Hill (pub.) 1995. Pp. 1535-1609."None>Shoffner and Wallace, 1995</a>; <a href="#2" class="mim-tip-reference" title="Arizmendi, J. M., Skehel, J. M., Runswick, M. J., Fearnley, I. M., Walker, J. E. <strong>Complementary DNA sequences of two 14.5 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Complementation of the primary structure of the complex.</strong> FEBS Lett. 313: 80-84, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1426273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1426273</a>] [<a href="https://doi.org/10.1016/0014-5793(92)81189-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1426273">Arizmendi et al., 1992</a>; <a href="#39" class="mim-tip-reference" title="Walker, J. E., Arizmendi, J. M., Dupuis, A., Fearnley, I. M., Finel, M., Medd, S. M., Pilkington, S. J., Runswick, M. J., Skehel, J. M. <strong>Sequences of 20 subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Application of a novel strategy for sequencing proteins using the polymerase chain reaction.</strong> J. Molec. Biol. 226: 1051, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1518044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1518044</a>] [<a href="https://doi.org/10.1016/0022-2836(92)91052-q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1518044">Walker et al., 1992</a>; <a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#3" class="mim-tip-reference" title="Attardi, G., Chomyn, A., Doolittle, R. F., Mariottini, P., Ragan, C. I. <strong>Seven unidentified reading frames of human mitochondrial DNA encode subunits of the respiratory chain NADH dehydrogenase.</strong> Cold Spring Harbor Symp. Quant. Biol. 51: 103-114, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3472707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3472707</a>] [<a href="https://doi.org/10.1101/sqb.1986.051.01.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3472707">Attardi et al., 1986</a>; Chomyn et al. (<a href="#11" class="mim-tip-reference" title="Chomyn, A., Mariottini, P., Cleeter, M. W. J., Ragan, C. I., Matsuno-Yagi, A., Hatefi, Y., Doolittle, R. G., Attardi, G. <strong>Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase.</strong> Nature 314: 592-597, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3921850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3921850</a>] [<a href="https://doi.org/10.1038/314592a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3921850">1985</a>, <a href="#10" class="mim-tip-reference" title="Chomyn, A., Cleeter, W. J., Ragan, C. I., Riley, M., Doolittle, R. F., Attardi, G. <strong>URF6, last unidentified reading frame of human mtDNA, codes for an NADH dehydrogenase subunit.</strong> Science 234: 614-618, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3764430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3764430</a>] [<a href="https://doi.org/10.1126/science.3764430" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3764430">1986</a>); <a href="#41" class="mim-tip-reference" title="Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J. <strong>Computer prediction of peptide maps: Assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two-dimensional-proteolytic digest gels.</strong> Am. J. Hum. Genet. 38: 461, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3518425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3518425</a>]" pmid="3518425">Wallace et al., 1986</a>; <a href="#28" class="mim-tip-reference" title="Oliver, N. A., Wallace, D. C. <strong>Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction.</strong> Molec. Cell. Biol. 2: 30-41, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6955589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6955589</a>] [<a href="https://doi.org/10.1128/mcb.2.1.30-41.1982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6955589">Oliver and Wallace, 1982</a>; <a href="#40" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the Committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). Complex I accepts electron from NADH, transfers them to ubiquinone (Coenzyme Q10) and uses the energy released to pump protons across the mitochondrial inner membrane. Complex I is more fully described under <a href="/entry/516000">516000</a>. MTND5 is probably a component of the hydrophobic protein fragment (<a href="#32" class="mim-tip-reference" title="Ragan, C. I. <strong>Structure of NADH-ubiquinone reductase (complex I).</strong> Curr. Top. Bioenerg. 15: 1-36, 1987."None>Ragan, 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6955589+3921850+1518044+3518425+3764430+3472707+7219534+1426273" 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>MTND5 is encoded by the guanine-rich heavy (H) strand of the mtDNA and located between nucleotide pairs (nps) 12337 and 14148 (<a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#40" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the Committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). It is maternally inherited along with the mtDNA (<a href="#14" class="mim-tip-reference" title="Giles, R. E., Blanc, H., Cann, H. M., Wallace, D. C. <strong>Maternal inheritance of human mitochondrial DNA.</strong> Proc. Nat. Acad. Sci. 77: 6715-6719, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6256757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6256757</a>] [<a href="https://doi.org/10.1073/pnas.77.11.6715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6256757">Giles et al., 1980</a>; <a href="#8" class="mim-tip-reference" title="Case, J. T., Wallace, D. C. <strong>Maternal inheritance of mitochondrial DNA polymorphisms in cultured human fibroblasts.</strong> Somat. Cell Genet. 7: 103-108, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261411</a>] [<a href="https://doi.org/10.1007/BF01544751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6261411">Case and Wallace, 1981</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7219534+6256757+6261411" 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>This gene encompasses 1811 nps of continuous coding sequence contained within a mRNA which begins with the AUA methionine start codon, ends with a UAA stop codon, and extends an additional 521 nps as 3-prime noncoding sequence before the polyadenosine tail begins. The 3-prime noncoding sequence of the MTND5 mRNA is the antisense sequence of the MTND6 sequence (<a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>). This mRNA is transcribed as a part of the polycistronic H-strand transcript, flanked by tRNALeu(CUN) and the 5-prime end and tRNA(Glu) on the 3-prime end. These tRNAs are cleaved from the transcript freeing transcript 5, the MTND5 mRNA. The mRNA is then polyadenylated (<a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#26" class="mim-tip-reference" title="Ojala, D., Montoya, J., Attardi, G. <strong>tRNA punctuation model of RNA processing in human mitochondria.</strong> Nature 290: 470-474, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219536</a>] [<a href="https://doi.org/10.1038/290470a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219536">Ojala et al., 1981</a>; <a href="#4" class="mim-tip-reference" title="Attardi, G., Chomyn, A., Montoya, J., Ojala, D. <strong>Identification and mapping of human mitochondrial genes.</strong> Cytogenet. Cell Genet. 32: 85-98, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7140372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7140372</a>] [<a href="https://doi.org/10.1159/000131689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7140372">Attardi et al., 1982</a>; <a href="#40" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the Committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7219534+7140372+7219536" 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 predicted polypeptide molecular mass is 66.6 kD (<a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>; <a href="#40" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the Committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). However, the apparent molecular mass on SDS-PAGE using Tris-glycine buffer is 43.5 kD (<a href="#41" class="mim-tip-reference" title="Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J. <strong>Computer prediction of peptide maps: Assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two-dimensional-proteolytic digest gels.</strong> Am. J. Hum. Genet. 38: 461, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3518425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3518425</a>]" pmid="3518425">Wallace et al., 1986</a>; <a href="#27" class="mim-tip-reference" title="Oliver, N. A., McCarthy, J., Wallace, D. C. <strong>Comparison of mitochondrially synthesized polypeptides of human, mouse, and monkey cell lines by a two-dimensional protease gel system.</strong> Somat. Cell Molec. Genet. 10: 639-643, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438810</a>] [<a href="https://doi.org/10.1007/BF01535230" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6438810">Oliver et al., 1984</a>), whereas using urea-phosphate buffer the molecular mass is 51 kD (<a href="#40" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the Committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7219534+3518425+6438810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Park, J. S., Sharma, L. K., Li, H., Xiang, R., Holstein, D., Wu, J., Lechleiter, J., Naylor, S. L., Deng, J. J., Lu, J., Bai, Y. <strong>A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis.</strong> Hum. Molec. Genet. 18: 1578-1589, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208652</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208652[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/ddp069" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208652">Park et al. (2009)</a> examined the contribution of mtDNA mutation and mitochondrial dysfunction in tumorigenesis using human cell lines carrying a frameshift in the MTND5 gene. With increasing mutant MTND5 mtDNA content, respiratory function (including oxygen consumption and ATP generation through oxidative phosphorylation) declined progressively, while lactate production and dependence on glucose increased. The reactive oxygen species (ROS) levels and apoptosis exhibited antagonistic pleiotropy associated with mitochondrial defects. The anchorage-dependence phenotype and tumor-forming capacity of cells carrying wildtype and mutant mtDNA were tested by growth assay in soft agar and subcutaneous implantation of the cells in nude mice. A cell line with a heteroplasmic MTND5 mutation showed significantly enhanced tumor growth, while cells with the same homoplasmic mutation inhibited tumor formation. Similar results were obtained from the analysis of a series of mouse cell lines carrying a MTND5 nonsense mutation. <a href="#29" class="mim-tip-reference" title="Park, J. S., Sharma, L. K., Li, H., Xiang, R., Holstein, D., Wu, J., Lechleiter, J., Naylor, S. L., Deng, J. J., Lu, J., Bai, Y. <strong>A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis.</strong> Hum. Molec. Genet. 18: 1578-1589, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208652</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208652[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/ddp069" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208652">Park et al. (2009)</a> hypothesized that the mtDNA mutations might play an important role in the early stage of cancer development, possibly through alteration of ROS generation and apoptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19208652" 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="#33" class="mim-tip-reference" title="Safra, M., Sas-Chen, A., Nir, R., Winkler, R., Nachshon, A., Bar-Yaacov, D., Erlacher, M., Rossmanith, W., Stern-Ginossar, N., Schwartz, S. <strong>The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution.</strong> Nature 551: 251-255, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29072297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29072297</a>] [<a href="https://doi.org/10.1038/nature24456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29072297">Safra et al. (2017)</a> developed an approach that allows the transcriptomewide mapping of N1-methyladenosine (m1A) at single-nucleotide resolution. Within the cytosol, m1A is present in a low number of mRNAs, typically at low stoichiometries, and almost invariably in tRNA T-loop-like structures, where it is introduced by the TRMT6/TRMT61A complex. <a href="#33" class="mim-tip-reference" title="Safra, M., Sas-Chen, A., Nir, R., Winkler, R., Nachshon, A., Bar-Yaacov, D., Erlacher, M., Rossmanith, W., Stern-Ginossar, N., Schwartz, S. <strong>The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution.</strong> Nature 551: 251-255, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29072297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29072297</a>] [<a href="https://doi.org/10.1038/nature24456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29072297">Safra et al. (2017)</a> identify a single m1A site in the mitochondrial ND5 mRNA, catalyzed by TRMT10C (<a href="/entry/615423">615423</a>), with methylation levels that are highly tissue-specific and tightly developmentally controlled. m1A leads to translational repression, probably through a mechanism involving ribosomal scanning or translation. <a href="#33" class="mim-tip-reference" title="Safra, M., Sas-Chen, A., Nir, R., Winkler, R., Nachshon, A., Bar-Yaacov, D., Erlacher, M., Rossmanith, W., Stern-Ginossar, N., Schwartz, S. <strong>The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution.</strong> Nature 551: 251-255, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29072297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29072297</a>] [<a href="https://doi.org/10.1038/nature24456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29072297">Safra et al. (2017)</a> concluded that their findings suggested that m1A on mRNA, probably because of its disruptive impact on basepairing, leads to translational repression, and is generally avoided by cells, while revealing 1 case in mitochondria where tight spatiotemporal control over m1A levels was adopted as a potential means of posttranscriptional regulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29072297" 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>Heteroplasmic mutations in the MTND5 gene can result in several different mitochondrial disorders, including Leber hereditary optic neuropathy (LHON; <a href="/entry/535000">535000</a>), MELAS syndrome (<a href="/entry/540000">540000</a>), Leigh syndrome (<a href="/entry/500017">500017</a>), and complex I deficiency (see <a href="/entry/252010">252010</a>).</p><p><a href="#25" class="mim-tip-reference" title="Nishigaki, Y., Marti, R., Hirano, M. <strong>ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy.</strong> Hum. Molec. Genet. 13: 91-101, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613972</a>] [<a href="https://doi.org/10.1093/hmg/ddh010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14613972">Nishigaki et al. (2004)</a> found that the MTND5 gene was a hotspot for mtDNA deletions in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE; <a href="/entry/603041">603041</a>), an autosomal recessive multisystem disorder associated with depletion, multiple deletions, and site-specific point mutations of mtDNA. MNGIE is caused by loss-of-function mutations in the ECGF1 gene (TYMP; <a href="/entry/131222">131222</a>), which result in increased levels of circulating thymidine and deoxyuridine. The authors postulated that alterations of pyrimidine nucleoside metabolism cause imbalances of mitochondrial nucleotide pools that, in turn, may cause somatic alterations of mtDNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14613972" 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>Among 116 patients suspected to have an oxidative phosphorylation disease and in whom common mitochondrial mutations had been excluded, <a href="#5" class="mim-tip-reference" title="Blok, M. J., Spruijt, L., de Coo, I. F. M., Schoonderwoerd, K., Hendrickx, A., Smeets, H. J. <strong>Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease.</strong> J. Med. Genet. 44: e74, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17400793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17400793</a>] [<a href="https://doi.org/10.1136/jmg.2006.045716" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17400793">Blok et al. (2007)</a> identified 14 pathogenic mutations in mitochondrial-encoded genes, 4 (27%) of which were in the MTND5 gene (see, e.g., <a href="#0007">516005.0007</a>; <a href="#0008">516005.0008</a>). The authors suggested that screening of this gene may be beneficial in routine diagnosis of these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17400793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Piccoli, C., Ripoli, M., Quarato, G., Scrima, R., D'Aprile, A., Boffoli, D., Margaglione, M., Criscuolo, C., De Michele, G., Sardanelli, A., Papa, S., Capitanio, N. <strong>Coexistence of mutations in PINK1 and mitochondrial DNA in early onset parkinsonism. (Letter)</strong> J. Med. Genet. 45: 596-602, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18524835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18524835</a>] [<a href="https://doi.org/10.1136/jmg.2008.058628" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18524835">Piccoli et al. (2008)</a> presented evidence that mutation in the MTND5 gene (<a href="#0010">516005.0010</a>) may modify the onset and severity of Parkinson disease (see, e.g., PARK6; <a href="/entry/605909">605909</a>) caused by nuclear mutations. See also <a href="/entry/556500">556500</a> for a discussion of Parkinson disease associated with mutations in mitochondrial genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18524835" 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>Restriction site polymorphisms have been identified at the following nucleotide position for the indicated enzymes (where '+' = site gain, '-' = site loss relative to the reference sequence, <a href="#1" class="mim-tip-reference" title="Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G. <strong>Sequence and organization of the human mitochondrial genome.</strong> Nature 290: 457-465, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>] [<a href="https://doi.org/10.1038/290457a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7219534">Anderson et al., 1981</a>): Alu I: -12560, +12763, +12990/12993/12996/13594, +13068, +13262, +13284, -14015; Ava II: -12629, -13367; BamHI: +13366, -14258; BstNI: -13704; Dde I: -12663, -12891, +12946, -13065, +13467; Hae II: +12949; Hae III: +13018, -13051, +13284, +13633, -13702, -13957; Hha I: +12940, +12950, -13208, +13940; HincII: +12026, -12406, -13259, -13634; HinfI: +12925, -13031, -13103, -13268, -13916; Hpa I: -12406; Mbo I: +12528, +12629, +12795/12798/12806/13374, +12849, +13004/13018/13182/13194, +13104, +13152, +13180, +13367, +13575; Msp I: +13100, +14139; Rsa I: +12345, +12345/12350/12528, +12810, +13096, -13325, +13542; Taq I: -13404, +13635, +14050/14366 (<a href="#40" class="mim-tip-reference" title="Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M. <strong>Report of the Committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong> Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845."None>Wallace et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=516005[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28359178 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28359178;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=rs28359178" 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=rs28359178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>This allele changes the moderately conserved alanine at amino acid 458 to a threonine (A458T). This mutation does not in itself appear to cause LHON, but is present in about 30% of Caucasian patients as compared to 6% of random population controls. The mutation is generally associated with the primary LHON mutations MTND6*LHON14484A (<a href="/entry/516006#0001">516006.0001</a>) and/or MTCYB*LHON15257A (<a href="/entry/516020#0001">516020.0001</a>) and occasionally with the secondary LHON mutations MTND2*LHON5244A (<a href="/entry/516001#0002">516001.0002</a>) and MTCYB*LHON15812A (<a href="/entry/516020#0002">516020.0002</a>). (<a href="#7" class="mim-tip-reference" title="Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., Wallace, D. C. <strong>Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.</strong> Genetics 130: 163-173, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1732158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1732158</a>] [<a href="https://doi.org/10.1093/genetics/130.1.163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1732158">Brown et al., 1992</a>; <a href="#16" class="mim-tip-reference" title="Johns, D. R., Berman, J. <strong>Alternative, simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic atrophy.</strong> Biochem. Biophys. Res. Commun. 174: 1324-1330, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1900003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1900003</a>] [<a href="https://doi.org/10.1016/0006-291x(91)91567-v" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1900003">Johns and Berman, 1991</a>; <a href="#17" class="mim-tip-reference" title="Johns, D. R., Neufeld, M. J., Park, R. D. <strong>An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy.</strong> Biochem. Biophys. Res. Commun. 187: 1551-1557, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1417830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1417830</a>] [<a href="https://doi.org/10.1016/0006-291x(92)90479-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1417830">Johns et al., 1992</a>; <a href="#18" class="mim-tip-reference" title="Johns, D. R., Neufeld, M. J. <strong>Cytochrome b mutations in Leber hereditary optic neuropathy.</strong> Biochem. Biophys. Res. Commun. 181: 1358-1364, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1764087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1764087</a>] [<a href="https://doi.org/10.1016/0006-291x(91)92088-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1764087">Johns and Neufeld, 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1764087+1732158+1900003+1417830" 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">rs387906425 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906425;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=rs387906425" 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=rs387906425" 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=RCV000010337 OR RCV004595478" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010337, RCV004595478" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010337...</a>
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<p>In a screening of bilateral optic atrophy patients who did not carry known primary LHON mutations, <a href="#15" class="mim-tip-reference" title="Howell, N., Halvorson, S., Burns, J., McCullough, D. A., Poulton, J. <strong>When does bilateral optic atrophy become Leber hereditary optic neuropathy? (Letter)</strong> Am. J. Hum. Genet. 53: 959-963, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213825</a>]" pmid="8213825">Howell et al. (1993)</a> identified 1 patient with a transition mutation at nucleotide 13730 that resulted in the substitution of glutamic acid for glycine at position 465 of the ND5 protein. The patient was heteroplasmic for the mutation, which the authors believed was the primary event contributing to bilateral optic atrophy. Studies suggested that the mutation was of recent origin, probably within the germline of the patient's mother. The mutation was similar to the primary LHON mutation at nucleotide 14484 in the ND6 protein (<a href="/entry/516006#0001">516006.0001</a>) in that it was weakly conserved and occurred within a hydrophobic region of the complex I region. Further, the patient with the 13730 mutation showed substantial recovery of vision, as do patients with the 14484 mutation. <a href="#15" class="mim-tip-reference" title="Howell, N., Halvorson, S., Burns, J., McCullough, D. A., Poulton, J. <strong>When does bilateral optic atrophy become Leber hereditary optic neuropathy? (Letter)</strong> Am. J. Hum. Genet. 53: 959-963, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213825</a>]" pmid="8213825">Howell et al. (1993)</a> suggested that the screening of a broad range of optic atrophies would result in identification of additional primary or secondary LHON mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8213825" 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">rs267606893 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606893;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=rs267606893" 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=rs267606893" 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=RCV000010338 OR RCV000144015 OR RCV002247308 OR RCV002260591" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010338, RCV000144015, RCV002247308, RCV002260591" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010338...</a>
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<p><a href="#38" class="mim-tip-reference" title="Taylor, R. W., Morris, A. A. M., Hutchinson, M., Turnbull, D. M. <strong>Leigh disease associated with a novel mitochondrial DNA ND5 mutation.</strong> Europ. J. Hum. Genet. 10: 141-144, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11938446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11938446</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200773" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11938446">Taylor et al. (2002)</a> reported a 12706T-C transition in the MTND5 gene in a patient with Leigh syndrome (<a href="/entry/500017">500017</a>) and specific complex I deficiency (33% of control value in muscle mitochondria) (<a href="/entry/252010">252010</a>). The mutation was heteroplasmic (43% mutant load in skeletal muscle and 30% mutant load in skin fibroblasts) and changed an invariant amino acid (phe124 to leu) in a highly conserved transmembrane helix of the protein. The patient presented at age 6 years with optic atrophy. At age 20, he complained of leg weakness, and over the next several years he developed ataxia, facial weakness, impaired hearing, ophthalmoplegia, and weakness of the muscles of mastication, palate, and larynx. He died at age 24. Neuropathology revealed symmetrical foci of neuronal loss, gliosis and microcapillary proliferation in the putamen, periaqueductal gray matter, inferior olives, and cerebellar cortex. There was no family history, but the family declined further investigation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11938446" 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">rs267606894 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606894;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=rs267606894" 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=rs267606894" 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=RCV000010339" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010339" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010339</a>
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<p>In a patient with MELAS syndrome (<a href="/entry/540000">540000</a>) characterized by focal neurologic dysfunction, increased CSF lactate, and abnormalities on MRI, <a href="#20" class="mim-tip-reference" title="Liolitsa, D., Rahman, S., Benton, S., Carr, L. J., Hanna, M. G. <strong>Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations?</strong> Ann. Neurol. 53: 128-132, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509858</a>] [<a href="https://doi.org/10.1002/ana.10435" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12509858">Liolitsa et al. (2003)</a> identified a heteroplasmic 12770A-G transition in the MTND5 gene, resulting in a glu145-to-gly (E145G) mutation. Skeletal muscle biopsy was normal, with no ragged-red fibers or COX-negative fibers. There was a 48% mutant load in muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509858" 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">rs267606895 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606895;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=rs267606895" 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=rs267606895" 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=RCV000010340 OR RCV000010341 OR RCV000010342 OR RCV004791209" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010340, RCV000010341, RCV000010342, RCV004791209" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010340...</a>
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<p>In a patient with phenotypic overlap of MELAS syndrome (<a href="/entry/540000">540000</a>), Leber optic atrophy (<a href="/entry/535000">535000</a>), and Leigh syndrome (<a href="/entry/500017">500017</a>), <a href="#20" class="mim-tip-reference" title="Liolitsa, D., Rahman, S., Benton, S., Carr, L. J., Hanna, M. G. <strong>Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations?</strong> Ann. Neurol. 53: 128-132, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509858</a>] [<a href="https://doi.org/10.1002/ana.10435" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12509858">Liolitsa et al. (2003)</a> identified a heteroplasmic 13045A-C transversion in the MTND5 gene, resulting in a met237-to-leu (M237L) mutation. The patient had neurologic symptoms including migraine, ataxia, seizures, cognitive impairment, lesions on MRI, and ocular abnormalities. Muscle biopsy showed no ragged-red fibers or COX-negative fibers, and complex I activity was mildly reduced (<a href="/entry/252010">252010</a>). Mutant load was 82% in muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509858" 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 LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606896 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606896;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=rs267606896" 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=rs267606896" 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=RCV000010343 OR RCV000010344 OR RCV004791210" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010343, RCV000010344, RCV004791210" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010343...</a>
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<p>In a patient with a progressive neurodegenerative disorder combining features of Leigh (<a href="/entry/500017">500017</a>) and MELAS (<a href="/entry/540000">540000</a>) syndromes, <a href="#12" class="mim-tip-reference" title="Crimi, M., Galbiati, S., Moroni, I., Bordoni, A., Perini, M. P., Lamantea, E., Sciacco, M., Zeviani, M., Biunno, I., Moggio, M., Scarlato, G., Comi, G. P. <strong>A missense mutation in the mitochondrial ND5 gene associated with a Leigh-MELAS overlap syndrome.</strong> Neurology 60: 1857-1861, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12796552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12796552</a>] [<a href="https://doi.org/10.1212/01.wnl.0000066048.72780.69" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12796552">Crimi et al. (2003)</a> identified a 13084A-T transversion in the MTND5 gene, resulting in a ser250-to-cys (S250C) substitution. Muscle biopsy revealed partial complex I deficiency (<a href="/entry/252010">252010</a>). The mutation was detected in a heteroplasmic state in the lymphocytes of the patient's mother (57%), who had migraine and optic atrophy, and younger sister (41%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12796552" 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 MELAS SYNDROME</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">rs267606897 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606897;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=rs267606897" 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=rs267606897" 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=RCV000010345 OR RCV000010346 OR RCV000144016 OR RCV000224472 OR RCV000494941" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010345, RCV000010346, RCV000144016, RCV000224472, RCV000494941" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010345...</a>
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<p>In a patient with MELAS syndrome (<a href="/entry/540000">540000</a>), <a href="#34" class="mim-tip-reference" title="Santorelli, F. M., Tanji, K., Kulikova, R., Shanske, S., Vilarinho, L., Hays, A. P., DiMauro, S. <strong>Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS.</strong> Biochem. Biophys. Res. Commun. 238: 326-328, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9299505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9299505</a>] [<a href="https://doi.org/10.1006/bbrc.1997.7167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9299505">Santorelli et al. (1997)</a> identified a heteroplasmic 13513G-A transition in the MTND5 gene, resulting in an asp393-to-asn (D393N) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9299505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Kirby, D. M., Boneh, A., Chow, C. W., Ohtake, A., Ryan, M. T., Thyagarajan, D., Thorburn, D. R. <strong>Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease.</strong> Ann. Neurol. 54: 473-478, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520659</a>] [<a href="https://doi.org/10.1002/ana.10687" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520659">Kirby et al. (2003)</a> identified the D393N mutation in 3 unrelated patients with Leigh syndrome (<a href="/entry/500017">500017</a>) and complex I deficiency (<a href="/entry/252010">252010</a>). The mutation was present in mutant loads of approximately 50% or less in all tissues tested, including multiple brain regions. The threshold mutant load for causing a complex I defect in cultured cells was approximately 30%. The findings suggested that the mutation causes a complex I defect when present at unusually low mutant loads and may act dominantly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 of 14 unrelated children with Leigh syndrome and complex I deficiency, <a href="#9" class="mim-tip-reference" title="Chol, M., Lebon, S., Benit, P., Chretien, D., de Lonlay, P., Goldenberg, A., Odent, S., Hertz-Pannier, L., Vincent-Delorme, C., Cormier-Daire, V., Rustin, P., Rotig, A., Munnich, A. <strong>The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency.</strong> J. Med. Genet. 40: 188-191, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12624137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12624137</a>] [<a href="https://doi.org/10.1136/jmg.40.3.188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12624137">Chol et al. (2003)</a> identified the D393N mutation in the MTND5 gene. All 3 children had a peculiar MRI aspect distinct from typical Leigh syndrome: brain MRI consistently showed a specific involvement of the substantia nigra and medulla oblongata sparing the basal ganglia. The mutation, which affects an evolutionarily conserved amino acid, had previously been observed in adult patients with MELAS syndrome or an overlap of Leber hereditary optic neuropathy (LHON; <a href="/entry/535000">535000</a>) and MELAS syndromes (<a href="#31" class="mim-tip-reference" title="Pulkes, T., Eunson, L., Patterson, V., Siddiqui, A., Wood, N. W., Nelson, I. P., Morgan-Hughes, J. A., Hanna, M. G. <strong>The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS.</strong> Ann. Neurol. 46: 916-919, 1999. Note: Erratum: Ann. Neurol. 47: 841 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10589546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10589546</a>] [<a href="https://doi.org/10.1002/1531-8249(199912)46:6<916::aid-ana16>3.0.co;2-r" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10589546">Pulkes et al., 1999</a>), emphasizing the clinical heterogeneity of mitochondrial DNA mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10589546+12624137" 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="#37" class="mim-tip-reference" title="Sudo, A., Honzawa, S., Nonaka, I., Goto, Y. <strong>Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and clinical features in Japan.</strong> J. Hum. Genet. 49: 92-96, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14730434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14730434</a>] [<a href="https://doi.org/10.1007/s10038-003-0116-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14730434">Sudo et al. (2004)</a> identified the D393N mutation in 6 of 84 (7%) Japanese patients with Leigh syndrome. The proportions of mutant mtDNA in muscles were relatively low (42 to 70%). The onset in patients with this mutation was delayed compared to those with the more common mutations at nucleotide 8993 in the MTATP6 gene (see <a href="/entry/516060#0001">516060.0001</a> and <a href="/entry/516060#0002">516060.0002</a>), and ptosis and cardiac conduction abnormalities were frequently seen (83%). <a href="#37" class="mim-tip-reference" title="Sudo, A., Honzawa, S., Nonaka, I., Goto, Y. <strong>Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and clinical features in Japan.</strong> J. Hum. Genet. 49: 92-96, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14730434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14730434</a>] [<a href="https://doi.org/10.1007/s10038-003-0116-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14730434">Sudo et al. (2004)</a> suggested that the 13513G-A mutation is a frequent cause of Leigh syndrome and that patients with this mutation may have a characteristic clinical course. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14730434" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a clinical presentation case, <a href="#13" class="mim-tip-reference" title="Dickerson, B. C., Holtzman, D., Grant, P. E., Tian, D. <strong>Case 36-2005: a 61-year-old woman with seizure, disturbed gait, and altered mental status.</strong> New Eng. J. Med. 353: 2271-2280, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16306525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16306525</a>] [<a href="https://doi.org/10.1056/NEJMcpc059032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16306525">Dickerson et al. (2005)</a> discussed a patient with the MELAS syndrome due to the 13513G-A mutation who had onset of her illness in her early sixties, making her the oldest patient with this syndrome known to carry that specific mutation. The onset of the clinical manifestations consisted of seizures and altered mental status at the age of 61 years. Difficulty hearing began about 6 months later. The patient died about 2 years after onset. <a href="#13" class="mim-tip-reference" title="Dickerson, B. C., Holtzman, D., Grant, P. E., Tian, D. <strong>Case 36-2005: a 61-year-old woman with seizure, disturbed gait, and altered mental status.</strong> New Eng. J. Med. 353: 2271-2280, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16306525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16306525</a>] [<a href="https://doi.org/10.1056/NEJMcpc059032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16306525">Dickerson et al. (2005)</a> stated that among the 6 reported patients with the MELAS syndrome and the 13513G-A mutation, all had the clinical features of the disorder, including hearing loss, by their mid-forties, and most were in their second decade at onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16306525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Blok, M. J., Spruijt, L., de Coo, I. F. M., Schoonderwoerd, K., Hendrickx, A., Smeets, H. J. <strong>Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease.</strong> J. Med. Genet. 44: e74, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17400793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17400793</a>] [<a href="https://doi.org/10.1136/jmg.2006.045716" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17400793">Blok et al. (2007)</a> reported 2 unrelated patients with oxidative phosphorylation defects associated with low levels of 13513G-A heteroplasmy. An 11-year-old girl presented with exercise intolerance and mild developmental delay. Brain MRI showed a subinsular cerebral infarct consistent with MELAS. She also had mild external ophthalmoplegia and strabismus. Skeletal muscle biopsy as an adult showed decreased complex I activity (58% of control). The mutation was present in blood (4 to 6%), fibroblasts (1 to 5%) and muscle (13 to 15%). A 5-month-old boy with a MELAS/Leigh phenotype showed failure to thrive, psychomotor retardation, retinitis pigmentosa, microcytic anemia, and characteristic brain lesions on MRI. He died at age 19 months after a viral infection. Skeletal muscle complex I activity was 8% of control; the mutation was present at 11 to 17% in blood, hair, and skeletal muscle. <a href="#5" class="mim-tip-reference" title="Blok, M. J., Spruijt, L., de Coo, I. F. M., Schoonderwoerd, K., Hendrickx, A., Smeets, H. J. <strong>Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease.</strong> J. Med. Genet. 44: e74, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17400793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17400793</a>] [<a href="https://doi.org/10.1136/jmg.2006.045716" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17400793">Blok et al. (2007)</a> noted that low loads of MTND5 mutations can still result in a severe clinical phenotype because ND5 synthesis is probably the rate-limiting step for the activity of complex I. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17400793" 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="#35" class="mim-tip-reference" title="Shanske, S., Coku, J., Lu, J., Ganesh, J., Krishna, S., Tanji, K., Bonilla, E., Naini, A. B., Hirano, M., DiMauro, S. <strong>The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome.</strong> Arch. Neurol. 65: 368-372, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18332249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18332249</a>] [<a href="https://doi.org/10.1001/archneurol.2007.67" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18332249">Shanske et al. (2008)</a> reported 12 patients with the 13513G-A mutation. The 3 adult patients had typical features of MELAS, whereas the other 9 infants and children had typical features of Leigh syndrome. Biochemical studies showed that complex I deficiency was inconsistent and generally mild, but mutation load in muscle and blood was relatively high. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18332249" 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">rs267606898 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606898;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=rs267606898" 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=rs267606898" 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=RCV000010347 OR RCV000010348 OR RCV000010349 OR RCV000854885 OR RCV002260592" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010347, RCV000010348, RCV000010349, RCV000854885, RCV002260592" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010347...</a>
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<p>In a 25-year-old man with MELAS syndrome (<a href="/entry/540000">540000</a>), <a href="#24" class="mim-tip-reference" title="Naini, A. B., Lu, J., Kaufmann, P., Bernstein, R. A., Mancuso, M., Bonilla, E., Hirano, M., DiMauro, S. <strong>Novel mitochondrial DNA ND5 mutation in a patient with clinical features of MELAS and MERRF.</strong> Arch. Neurol. 62: 473-476, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15767514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15767514</a>] [<a href="https://doi.org/10.1001/archneur.62.3.473" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15767514">Naini et al. (2005)</a> identified a heteroplasmic 13042G-A transition in the MTND5 gene, resulting in an ala236-to-thr (A236T) substitution. The patient had normal psychomotor development until age 17 years, when he had a tonic-clonic seizure. At age 20 years, he had a severe stroke necessitating prolonged rehabilitation. In the following years, he experienced more stroke-like episodes, partial seizures, memory loss, migraine-like headaches, myoclonus, exercise intolerance, and osteoporosis with vertebral fracture. <a href="#24" class="mim-tip-reference" title="Naini, A. B., Lu, J., Kaufmann, P., Bernstein, R. A., Mancuso, M., Bonilla, E., Hirano, M., DiMauro, S. <strong>Novel mitochondrial DNA ND5 mutation in a patient with clinical features of MELAS and MERRF.</strong> Arch. Neurol. 62: 473-476, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15767514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15767514</a>] [<a href="https://doi.org/10.1001/archneur.62.3.473" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15767514">Naini et al. (2005)</a> noted the similarities to MERRF syndrome (<a href="/entry/545000">545000</a>), although there were no ragged-red fibers on muscle biopsy. Muscle biopsy showed decreased activity of complex I. The mutation was heteroplasmic in both muscle (90%) and blood (50%). The patient's mother reportedly had multiple strokes and seizures since her thirties, as well as migraine headaches and mild hearing loss. She did not have myoclonus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15767514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Blok, M. J., Spruijt, L., de Coo, I. F. M., Schoonderwoerd, K., Hendrickx, A., Smeets, H. J. <strong>Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease.</strong> J. Med. Genet. 44: e74, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17400793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17400793</a>] [<a href="https://doi.org/10.1136/jmg.2006.045716" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17400793">Blok et al. (2007)</a> reported a boy with a Leigh-like syndrome (<a href="/entry/500017">500017</a>) who was heteroplasmic for the 13042G-A mutation, which was identified in blood (77%), muscle (84%), and fibroblasts (86%). He presented at age 3 years with ataxia, internuclear ophthalmoplegia, increased serum and CSF lactate, and hyperintensities in the pons and midbrain. Skeletal muscle histology was normal. The patient's unaffected mother and grandmother also carried the mutation at much lower levels (2 to 25% in various tissues). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17400793" 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">rs267606899 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606899;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=rs267606899" 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=rs267606899" 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=RCV000010350" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010350" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010350</a>
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<p>In a man with Leber optic atrophy (<a href="/entry/535000">535000</a>) with onset at age 20 years, <a href="#22" class="mim-tip-reference" title="Mayorov, V., Biousse, V., Newman, N. J., Brown, M. D. <strong>The role of the ND5 gene in LHON: characterization of a new, heteroplasmic LHON mutation.</strong> Ann. Neurol. 58: 807-811, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16240359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16240359</a>] [<a href="https://doi.org/10.1002/ana.20669" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16240359">Mayorov et al. (2005)</a> identified a heteroplasmic 12848C-T transition in a highly conserved region of the MTND5 gene, resulting in an ala171-to-val (A171V) substitution. Lymphoblasts derived from the proband contained 54% mutant mtDNA, whereas lymphoblasts from his unaffected mother contained 37% mutant mtDNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16240359" 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 PARKINSON DISEASE 6, MODIFIER OF</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">rs1556424100 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1556424100;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=rs1556424100" 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=rs1556424100" 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=RCV000010351 OR RCV000854803" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000010351, RCV000854803" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000010351...</a>
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<p>In a patient with early-onset Parkinson disease (PARK6; <a href="/entry/605909">605909</a>) due to a homozygous mutation in the PINK1 gene (<a href="/entry/608309#0002">608309.0002</a>), <a href="#30" class="mim-tip-reference" title="Piccoli, C., Ripoli, M., Quarato, G., Scrima, R., D'Aprile, A., Boffoli, D., Margaglione, M., Criscuolo, C., De Michele, G., Sardanelli, A., Papa, S., Capitanio, N. <strong>Coexistence of mutations in PINK1 and mitochondrial DNA in early onset parkinsonism. (Letter)</strong> J. Med. Genet. 45: 596-602, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18524835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18524835</a>] [<a href="https://doi.org/10.1136/jmg.2008.058628" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18524835">Piccoli et al. (2008)</a> identified a homoplasmic 12397A-G mutation in the MTND5 gene and a homoplasmic mutation in the MTND6 gene (<a href="/entry/516006#0008">516006.0008</a>). The 12397A-G mutation results in a thr21-to-ala (T21A) substitution in a hydrophilic segment that is likely exposed to the intermembrane mitochondrial space. The patient had onset at age 22 years. His mother, who was heterozygous for the PINK1 mutation, was also homoplasmic for both mitochondrial mutations and showed disease onset at age 53. The father, who was heterozygous for the PINK1 mutation only, was unaffected at age 79. Biochemical studies of the proband's fibroblasts showed mitochondrial dysfunction, with decreased amounts of cytochrome c oxidase, impaired complex I activity, and increased hydrogen peroxide generation. <a href="#30" class="mim-tip-reference" title="Piccoli, C., Ripoli, M., Quarato, G., Scrima, R., D'Aprile, A., Boffoli, D., Margaglione, M., Criscuolo, C., De Michele, G., Sardanelli, A., Papa, S., Capitanio, N. <strong>Coexistence of mutations in PINK1 and mitochondrial DNA in early onset parkinsonism. (Letter)</strong> J. Med. Genet. 45: 596-602, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18524835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18524835</a>] [<a href="https://doi.org/10.1136/jmg.2008.058628" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18524835">Piccoli et al. (2008)</a> concluded that the presence of the mitochondrial mutations in combination with the PINK1 mutation may have accelerated the onset of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18524835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 LEBER OPTIC ATROPHY</strong>
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MTND5, 12338T-C, MET1THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs201863060 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201863060;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=rs201863060" 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=rs201863060" 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=RCV000022893 OR RCV000854787" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022893, RCV000854787" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022893...</a>
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<p><a href="#21" class="mim-tip-reference" title="Liu, X.-L., Zhou, X., Zhou, J., Zhao, F., Zhang, J., Li, C., Ji, Y., Zhang, Y., Wei, Q.-P., Sun, Y.-H., Yang, L., Lin, B., Yuan, Y., Li, Y., Qu, J., Guan, M.-X. <strong>Leber's hereditary optic neuropathy is associated with the T12338C mutation in mitochondrial ND5 gene in six Han Chinese families.</strong> Ophthalmology 118: 978-985, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21131053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21131053</a>] [<a href="https://doi.org/10.1016/j.ophtha.2010.09.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21131053">Liu et al. (2011)</a> investigated the molecular pathogenesis of LHON (<a href="/entry/535000">535000</a>) in 6 Han Chinese families in which 9 (6 males/3 females) of 86 matrilineal relatives exhibited variable severity and age of onset of optic neuropathy. The average age of onset was 20 years and the penetrance of visual impairment averaged 10.8%. Molecular analysis of mtDNA in these families identified the homoplasmic ND5 12338T-C mutation and a distinct set of variants belonging to the Asian haplogroup F2. The mutation resulted in the replacement of the first amino acid, translation-initiating methionine with a threonine (M1T). This methionine in ND5 is an extraordinarily conserved residue from bacteria to human mitochondria. The 12338T-C mutation was present in the maternal lineage of the 6 pedigrees and not in 178 Chinese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21131053" 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="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>See Also:</strong>
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<a href="#Brown1992" class="mim-tip-reference" title="Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., Wallace, D. C. <strong>Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.</strong> Genetics 130: 163-173, 1992.">Brown et al. (1992)</a>; <a href="#Montoya1981" class="mim-tip-reference" title="Montoya, J., Ojala, D., Attardi, G. <strong>Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs.</strong> Nature 290: 465-470, 1981.">Montoya et al. (1981)</a>
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<strong>REFERENCES</strong>
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Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G.
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<strong>Sequence and organization of the human mitochondrial genome.</strong>
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Nature 290: 457-465, 1981.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219534" 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/10.1038/290457a0" target="_blank">Full Text</a>]
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Arizmendi, J. M., Skehel, J. M., Runswick, M. J., Fearnley, I. M., Walker, J. E.
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<strong>Complementary DNA sequences of two 14.5 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Complementation of the primary structure of the complex.</strong>
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FEBS Lett. 313: 80-84, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1426273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1426273</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1426273" 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/10.1016/0014-5793(92)81189-s" target="_blank">Full Text</a>]
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<a id="Attardi1986" class="mim-anchor"></a>
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Attardi, G., Chomyn, A., Doolittle, R. F., Mariottini, P., Ragan, C. I.
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<strong>Seven unidentified reading frames of human mitochondrial DNA encode subunits of the respiratory chain NADH dehydrogenase.</strong>
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Cold Spring Harbor Symp. Quant. Biol. 51: 103-114, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3472707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3472707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3472707" 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/10.1101/sqb.1986.051.01.013" target="_blank">Full Text</a>]
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<a id="Attardi1982" class="mim-anchor"></a>
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Attardi, G., Chomyn, A., Montoya, J., Ojala, D.
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<strong>Identification and mapping of human mitochondrial genes.</strong>
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Cytogenet. Cell Genet. 32: 85-98, 1982.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7140372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7140372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7140372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000131689" target="_blank">Full Text</a>]
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Blok, M. J., Spruijt, L., de Coo, I. F. M., Schoonderwoerd, K., Hendrickx, A., Smeets, H. J.
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<strong>Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease.</strong>
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J. Med. Genet. 44: e74, 2007. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17400793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17400793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17400793" 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/10.1136/jmg.2006.045716" target="_blank">Full Text</a>]
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<a id="Brown1992" class="mim-anchor"></a>
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Brown, M. D., Voljavec, A. S., Lott, M. T., MacDonald, I., Wallace, D. C.
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<strong>Leber's hereditary optic neuropathy; a model for mitochondrial neurodegenerative diseases.</strong>
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FASEB J. 6: 2791-2799, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1634041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1634041</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1634041" 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/10.1096/fasebj.6.10.1634041" target="_blank">Full Text</a>]
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Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., Wallace, D. C.
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<strong>Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.</strong>
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Genetics 130: 163-173, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1732158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1732158</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1732158" 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/genetics/130.1.163" target="_blank">Full Text</a>]
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Case, J. T., Wallace, D. C.
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<strong>Maternal inheritance of mitochondrial DNA polymorphisms in cultured human fibroblasts.</strong>
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Somat. Cell Genet. 7: 103-108, 1981.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261411</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6261411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF01544751" target="_blank">Full Text</a>]
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Chol, M., Lebon, S., Benit, P., Chretien, D., de Lonlay, P., Goldenberg, A., Odent, S., Hertz-Pannier, L., Vincent-Delorme, C., Cormier-Daire, V., Rustin, P., Rotig, A., Munnich, A.
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<strong>The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency.</strong>
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J. Med. Genet. 40: 188-191, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12624137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12624137</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12624137" 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/10.1136/jmg.40.3.188" target="_blank">Full Text</a>]
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Chomyn, A., Cleeter, W. J., Ragan, C. I., Riley, M., Doolittle, R. F., Attardi, G.
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<strong>URF6, last unidentified reading frame of human mtDNA, codes for an NADH dehydrogenase subunit.</strong>
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Science 234: 614-618, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3764430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3764430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3764430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.3764430" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Chomyn1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chomyn, A., Mariottini, P., Cleeter, M. W. J., Ragan, C. I., Matsuno-Yagi, A., Hatefi, Y., Doolittle, R. G., Attardi, G.
|
|
<strong>Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase.</strong>
|
|
Nature 314: 592-597, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3921850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3921850</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3921850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/314592a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Crimi2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crimi, M., Galbiati, S., Moroni, I., Bordoni, A., Perini, M. P., Lamantea, E., Sciacco, M., Zeviani, M., Biunno, I., Moggio, M., Scarlato, G., Comi, G. P.
|
|
<strong>A missense mutation in the mitochondrial ND5 gene associated with a Leigh-MELAS overlap syndrome.</strong>
|
|
Neurology 60: 1857-1861, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12796552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12796552</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12796552" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000066048.72780.69" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Dickerson2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dickerson, B. C., Holtzman, D., Grant, P. E., Tian, D.
|
|
<strong>Case 36-2005: a 61-year-old woman with seizure, disturbed gait, and altered mental status.</strong>
|
|
New Eng. J. Med. 353: 2271-2280, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16306525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16306525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16306525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMcpc059032" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Giles1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giles, R. E., Blanc, H., Cann, H. M., Wallace, D. C.
|
|
<strong>Maternal inheritance of human mitochondrial DNA.</strong>
|
|
Proc. Nat. Acad. Sci. 77: 6715-6719, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6256757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6256757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6256757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.77.11.6715" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Howell1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Howell, N., Halvorson, S., Burns, J., McCullough, D. A., Poulton, J.
|
|
<strong>When does bilateral optic atrophy become Leber hereditary optic neuropathy? (Letter)</strong>
|
|
Am. J. Hum. Genet. 53: 959-963, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8213825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8213825</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8213825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Johns1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Berman, J.
|
|
<strong>Alternative, simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic atrophy.</strong>
|
|
Biochem. Biophys. Res. Commun. 174: 1324-1330, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1900003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1900003</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1900003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(91)91567-v" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Johns1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Neufeld, M. J., Park, R. D.
|
|
<strong>An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy.</strong>
|
|
Biochem. Biophys. Res. Commun. 187: 1551-1557, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1417830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1417830</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1417830" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(92)90479-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Johns1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Neufeld, M. J.
|
|
<strong>Cytochrome b mutations in Leber hereditary optic neuropathy.</strong>
|
|
Biochem. Biophys. Res. Commun. 181: 1358-1364, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1764087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1764087</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1764087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0006-291x(91)92088-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Kirby2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kirby, D. M., Boneh, A., Chow, C. W., Ohtake, A., Ryan, M. T., Thyagarajan, D., Thorburn, D. R.
|
|
<strong>Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease.</strong>
|
|
Ann. Neurol. 54: 473-478, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520659</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.10687" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Liolitsa2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liolitsa, D., Rahman, S., Benton, S., Carr, L. J., Hanna, M. G.
|
|
<strong>Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations?</strong>
|
|
Ann. Neurol. 53: 128-132, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.10435" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Liu2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liu, X.-L., Zhou, X., Zhou, J., Zhao, F., Zhang, J., Li, C., Ji, Y., Zhang, Y., Wei, Q.-P., Sun, Y.-H., Yang, L., Lin, B., Yuan, Y., Li, Y., Qu, J., Guan, M.-X.
|
|
<strong>Leber's hereditary optic neuropathy is associated with the T12338C mutation in mitochondrial ND5 gene in six Han Chinese families.</strong>
|
|
Ophthalmology 118: 978-985, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21131053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21131053</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21131053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ophtha.2010.09.003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Mayorov2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mayorov, V., Biousse, V., Newman, N. J., Brown, M. D.
|
|
<strong>The role of the ND5 gene in LHON: characterization of a new, heteroplasmic LHON mutation.</strong>
|
|
Ann. Neurol. 58: 807-811, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16240359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16240359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16240359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.20669" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Montoya1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montoya, J., Ojala, D., Attardi, G.
|
|
<strong>Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs.</strong>
|
|
Nature 290: 465-470, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219535</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219535" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/290465a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Naini2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Naini, A. B., Lu, J., Kaufmann, P., Bernstein, R. A., Mancuso, M., Bonilla, E., Hirano, M., DiMauro, S.
|
|
<strong>Novel mitochondrial DNA ND5 mutation in a patient with clinical features of MELAS and MERRF.</strong>
|
|
Arch. Neurol. 62: 473-476, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15767514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15767514</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15767514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.62.3.473" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Nishigaki2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nishigaki, Y., Marti, R., Hirano, M.
|
|
<strong>ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy.</strong>
|
|
Hum. Molec. Genet. 13: 91-101, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14613972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddh010" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Ojala1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ojala, D., Montoya, J., Attardi, G.
|
|
<strong>tRNA punctuation model of RNA processing in human mitochondria.</strong>
|
|
Nature 290: 470-474, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7219536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7219536</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7219536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/290470a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Oliver1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., McCarthy, J., Wallace, D. C.
|
|
<strong>Comparison of mitochondrially synthesized polypeptides of human, mouse, and monkey cell lines by a two-dimensional protease gel system.</strong>
|
|
Somat. Cell Molec. Genet. 10: 639-643, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6438810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6438810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6438810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/BF01535230" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Oliver1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., Wallace, D. C.
|
|
<strong>Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction.</strong>
|
|
Molec. Cell. Biol. 2: 30-41, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6955589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6955589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6955589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/mcb.2.1.30-41.1982" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Park2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Park, J. S., Sharma, L. K., Li, H., Xiang, R., Holstein, D., Wu, J., Lechleiter, J., Naylor, S. L., Deng, J. J., Lu, J., Bai, Y.
|
|
<strong>A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis.</strong>
|
|
Hum. Molec. Genet. 18: 1578-1589, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208652</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208652[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=19208652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp069" target="_blank">Full Text</a>]
|
|
|
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|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Piccoli2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Piccoli, C., Ripoli, M., Quarato, G., Scrima, R., D'Aprile, A., Boffoli, D., Margaglione, M., Criscuolo, C., De Michele, G., Sardanelli, A., Papa, S., Capitanio, N.
|
|
<strong>Coexistence of mutations in PINK1 and mitochondrial DNA in early onset parkinsonism. (Letter)</strong>
|
|
J. Med. Genet. 45: 596-602, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18524835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18524835</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18524835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2008.058628" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Pulkes1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pulkes, T., Eunson, L., Patterson, V., Siddiqui, A., Wood, N. W., Nelson, I. P., Morgan-Hughes, J. A., Hanna, M. G.
|
|
<strong>The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS.</strong>
|
|
Ann. Neurol. 46: 916-919, 1999. Note: Erratum: Ann. Neurol. 47: 841 only, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10589546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10589546</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10589546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1531-8249(199912)46:6<916::aid-ana16>3.0.co;2-r" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Ragan1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ragan, C. I.
|
|
<strong>Structure of NADH-ubiquinone reductase (complex I).</strong>
|
|
Curr. Top. Bioenerg. 15: 1-36, 1987.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Safra2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Safra, M., Sas-Chen, A., Nir, R., Winkler, R., Nachshon, A., Bar-Yaacov, D., Erlacher, M., Rossmanith, W., Stern-Ginossar, N., Schwartz, S.
|
|
<strong>The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution.</strong>
|
|
Nature 551: 251-255, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29072297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29072297</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29072297" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature24456" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Santorelli1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Santorelli, F. M., Tanji, K., Kulikova, R., Shanske, S., Vilarinho, L., Hays, A. P., DiMauro, S.
|
|
<strong>Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS.</strong>
|
|
Biochem. Biophys. Res. Commun. 238: 326-328, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9299505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9299505</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9299505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1997.7167" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Shanske2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Shanske, S., Coku, J., Lu, J., Ganesh, J., Krishna, S., Tanji, K., Bonilla, E., Naini, A. B., Hirano, M., DiMauro, S.
|
|
<strong>The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome.</strong>
|
|
Arch. Neurol. 65: 368-372, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18332249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18332249</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18332249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneurol.2007.67" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Shoffner1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shoffner, J. M., Wallace, D. C.
|
|
<strong>Oxidative phosphorylation diseases.In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. Vol. 1.</strong>
|
|
New York: McGraw-Hill (pub.) 1995. Pp. 1535-1609.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Sudo2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sudo, A., Honzawa, S., Nonaka, I., Goto, Y.
|
|
<strong>Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and clinical features in Japan.</strong>
|
|
J. Hum. Genet. 49: 92-96, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14730434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14730434</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14730434" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10038-003-0116-1" target="_blank">Full Text</a>]
|
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|
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|
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|
|
|
|
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|
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|
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|
|
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|
|
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|
|
Taylor, R. W., Morris, A. A. M., Hutchinson, M., Turnbull, D. M.
|
|
<strong>Leigh disease associated with a novel mitochondrial DNA ND5 mutation.</strong>
|
|
Europ. J. Hum. Genet. 10: 141-144, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11938446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11938446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11938446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
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[<a href="https://doi.org/10.1038/sj.ejhg.5200773" target="_blank">Full Text</a>]
|
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|
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|
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|
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|
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|
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|
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<a id="Walker1992" class="mim-anchor"></a>
|
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|
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Walker, J. E., Arizmendi, J. M., Dupuis, A., Fearnley, I. M., Finel, M., Medd, S. M., Pilkington, S. J., Runswick, M. J., Skehel, J. M.
|
|
<strong>Sequences of 20 subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Application of a novel strategy for sequencing proteins using the polymerase chain reaction.</strong>
|
|
J. Molec. Biol. 226: 1051, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1518044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1518044</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1518044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1016/0022-2836(92)91052-q" target="_blank">Full Text</a>]
|
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|
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|
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|
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|
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Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M.
|
|
<strong>Report of the Committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong>
|
|
Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845.
|
|
|
|
|
|
|
|
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|
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</p>
|
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|
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Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J.
|
|
<strong>Computer prediction of peptide maps: Assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two-dimensional-proteolytic digest gels.</strong>
|
|
Am. J. Hum. Genet. 38: 461, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3518425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3518425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3518425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<span class="mim-text-font">
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Ada Hamosh - updated : 02/08/2018
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<span class="mim-text-font">
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Jane Kelly - updated : 8/26/2011<br>George E. Tiller - updated : 10/15/2009<br>Cassandra L. Kniffin - updated : 1/12/2009<br>Cassandra L. Kniffin - updated : 10/6/2008<br>Cassandra L. Kniffin - updated : 5/30/2007<br>Cassandra L. Kniffin - updated : 3/31/2006<br>George E. Tiller - updated : 3/7/2006<br>Victor A. McKusick - updated : 2/16/2006<br>Cassandra L. Kniffin - updated : 6/27/2005<br>Marla J. F. O'Neill - updated : 3/18/2004<br>Victor A. McKusick - updated : 3/1/2004<br>Cassandra L. Kniffin - updated : 1/7/2004<br>Cassandra L. Kniffin - updated : 8/11/2003<br>Cassandra L. Kniffin - updated : 3/6/2003<br>Michael B. Petersen - updated : 10/22/2002<br>Jane Kelly - updated : 4/2/2002<br>Douglas C. Wallace - updated : 4/6/1994
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Victor A. McKusick : 3/2/1993
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carol : 05/20/2024
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carol : 05/15/2024<br>carol : 02/09/2018<br>alopez : 02/08/2018<br>carol : 07/08/2016<br>carol : 8/30/2011<br>terry : 8/26/2011<br>terry : 5/24/2011<br>terry : 11/3/2010<br>carol : 1/19/2010<br>wwang : 10/20/2009<br>terry : 10/15/2009<br>wwang : 8/21/2009<br>wwang : 1/20/2009<br>ckniffin : 1/12/2009<br>wwang : 10/7/2008<br>ckniffin : 10/6/2008<br>terry : 8/26/2008<br>terry : 8/26/2008<br>wwang : 6/6/2007<br>ckniffin : 5/30/2007<br>wwang : 4/6/2006<br>ckniffin : 3/31/2006<br>wwang : 3/7/2006<br>alopez : 3/6/2006<br>terry : 2/16/2006<br>carol : 9/21/2005<br>ckniffin : 8/29/2005<br>wwang : 7/14/2005<br>wwang : 7/13/2005<br>ckniffin : 6/27/2005<br>tkritzer : 3/22/2004<br>tkritzer : 3/18/2004<br>tkritzer : 3/2/2004<br>terry : 3/1/2004<br>tkritzer : 1/14/2004<br>ckniffin : 1/7/2004<br>tkritzer : 8/19/2003<br>ckniffin : 8/11/2003<br>ckniffin : 8/11/2003<br>tkritzer : 4/8/2003<br>tkritzer : 4/8/2003<br>ckniffin : 3/6/2003<br>ckniffin : 3/6/2003<br>carol : 10/22/2002<br>cwells : 4/2/2002<br>joanna : 9/17/2001<br>dkim : 12/15/1998<br>dholmes : 5/11/1998<br>dholmes : 5/11/1998<br>terry : 1/21/1997<br>mark : 4/9/1996<br>mimman : 2/8/1996<br>mark : 6/19/1995<br>pfoster : 8/16/1994<br>mimadm : 5/17/1994<br>carol : 2/28/1994<br>carol : 10/11/1993
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<h3>
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<span class="mim-font">
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<strong>*</strong> 516005
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</h3>
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<h3>
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<span class="mim-font">
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COMPLEX I, SUBUNIT ND5; MTND5
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</h3>
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<br />
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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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<h4>
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<span class="mim-font">
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NADH-UBIQUINONE OXIDOREDUCTASE, SUBUNIT ND5<br />
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NADH DEHYDROGENASE, SUBUNIT 5
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</h4>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: MT-ND5</em></strong>
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<strong>SNOMEDCT:</strong> 230426003, 39925003, 58610003;
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<strong>ICD10CM:</strong> E88.41, E88.42, H47.22;
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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<p>Subunit 5 is 1 of the 7 mitochondrial DNA (mtDNA) encoded subunits (MTND1, MTND2, MTND3, MTND4L, MTND4, MTND5, MTND6) included among the approximately 41 polypeptides of respiratory complex I (NADH:ubiquinone oxidoreductase, EC 1.6.5.3)(Shoffner and Wallace, 1995; Arizmendi et al., 1992; Walker et al., 1992; Anderson et al., 1981; Attardi et al., 1986; Chomyn et al. (1985, 1986); Wallace et al., 1986; Oliver and Wallace, 1982; Wallace et al., 1994). Complex I accepts electron from NADH, transfers them to ubiquinone (Coenzyme Q10) and uses the energy released to pump protons across the mitochondrial inner membrane. Complex I is more fully described under 516000. MTND5 is probably a component of the hydrophobic protein fragment (Ragan, 1987). </p>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</h4>
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<span class="mim-text-font">
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<p>MTND5 is encoded by the guanine-rich heavy (H) strand of the mtDNA and located between nucleotide pairs (nps) 12337 and 14148 (Anderson et al., 1981; Wallace et al., 1994). It is maternally inherited along with the mtDNA (Giles et al., 1980; Case and Wallace, 1981). </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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<span class="mim-text-font">
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<p>This gene encompasses 1811 nps of continuous coding sequence contained within a mRNA which begins with the AUA methionine start codon, ends with a UAA stop codon, and extends an additional 521 nps as 3-prime noncoding sequence before the polyadenosine tail begins. The 3-prime noncoding sequence of the MTND5 mRNA is the antisense sequence of the MTND6 sequence (Anderson et al., 1981). This mRNA is transcribed as a part of the polycistronic H-strand transcript, flanked by tRNALeu(CUN) and the 5-prime end and tRNA(Glu) on the 3-prime end. These tRNAs are cleaved from the transcript freeing transcript 5, the MTND5 mRNA. The mRNA is then polyadenylated (Anderson et al., 1981; Ojala et al., 1981; Attardi et al., 1982; Wallace et al., 1994). </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>The predicted polypeptide molecular mass is 66.6 kD (Anderson et al., 1981; Wallace et al., 1994). However, the apparent molecular mass on SDS-PAGE using Tris-glycine buffer is 43.5 kD (Wallace et al., 1986; Oliver et al., 1984), whereas using urea-phosphate buffer the molecular mass is 51 kD (Wallace et al., 1994). </p><p>Park et al. (2009) examined the contribution of mtDNA mutation and mitochondrial dysfunction in tumorigenesis using human cell lines carrying a frameshift in the MTND5 gene. With increasing mutant MTND5 mtDNA content, respiratory function (including oxygen consumption and ATP generation through oxidative phosphorylation) declined progressively, while lactate production and dependence on glucose increased. The reactive oxygen species (ROS) levels and apoptosis exhibited antagonistic pleiotropy associated with mitochondrial defects. The anchorage-dependence phenotype and tumor-forming capacity of cells carrying wildtype and mutant mtDNA were tested by growth assay in soft agar and subcutaneous implantation of the cells in nude mice. A cell line with a heteroplasmic MTND5 mutation showed significantly enhanced tumor growth, while cells with the same homoplasmic mutation inhibited tumor formation. Similar results were obtained from the analysis of a series of mouse cell lines carrying a MTND5 nonsense mutation. Park et al. (2009) hypothesized that the mtDNA mutations might play an important role in the early stage of cancer development, possibly through alteration of ROS generation and apoptosis. </p><p>Safra et al. (2017) developed an approach that allows the transcriptomewide mapping of N1-methyladenosine (m1A) at single-nucleotide resolution. Within the cytosol, m1A is present in a low number of mRNAs, typically at low stoichiometries, and almost invariably in tRNA T-loop-like structures, where it is introduced by the TRMT6/TRMT61A complex. Safra et al. (2017) identify a single m1A site in the mitochondrial ND5 mRNA, catalyzed by TRMT10C (615423), with methylation levels that are highly tissue-specific and tightly developmentally controlled. m1A leads to translational repression, probably through a mechanism involving ribosomal scanning or translation. Safra et al. (2017) concluded that their findings suggested that m1A on mRNA, probably because of its disruptive impact on basepairing, leads to translational repression, and is generally avoided by cells, while revealing 1 case in mitochondria where tight spatiotemporal control over m1A levels was adopted as a potential means of posttranscriptional regulation. </p>
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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>Heteroplasmic mutations in the MTND5 gene can result in several different mitochondrial disorders, including Leber hereditary optic neuropathy (LHON; 535000), MELAS syndrome (540000), Leigh syndrome (500017), and complex I deficiency (see 252010).</p><p>Nishigaki et al. (2004) found that the MTND5 gene was a hotspot for mtDNA deletions in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE; 603041), an autosomal recessive multisystem disorder associated with depletion, multiple deletions, and site-specific point mutations of mtDNA. MNGIE is caused by loss-of-function mutations in the ECGF1 gene (TYMP; 131222), which result in increased levels of circulating thymidine and deoxyuridine. The authors postulated that alterations of pyrimidine nucleoside metabolism cause imbalances of mitochondrial nucleotide pools that, in turn, may cause somatic alterations of mtDNA. </p><p>Among 116 patients suspected to have an oxidative phosphorylation disease and in whom common mitochondrial mutations had been excluded, Blok et al. (2007) identified 14 pathogenic mutations in mitochondrial-encoded genes, 4 (27%) of which were in the MTND5 gene (see, e.g., 516005.0007; 516005.0008). The authors suggested that screening of this gene may be beneficial in routine diagnosis of these patients. </p><p>Piccoli et al. (2008) presented evidence that mutation in the MTND5 gene (516005.0010) may modify the onset and severity of Parkinson disease (see, e.g., PARK6; 605909) caused by nuclear mutations. See also 556500 for a discussion of Parkinson disease associated with mutations in mitochondrial genes. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genetic Variability</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>Restriction site polymorphisms have been identified at the following nucleotide position for the indicated enzymes (where '+' = site gain, '-' = site loss relative to the reference sequence, Anderson et al., 1981): Alu I: -12560, +12763, +12990/12993/12996/13594, +13068, +13262, +13284, -14015; Ava II: -12629, -13367; BamHI: +13366, -14258; BstNI: -13704; Dde I: -12663, -12891, +12946, -13065, +13467; Hae II: +12949; Hae III: +13018, -13051, +13284, +13633, -13702, -13957; Hha I: +12940, +12950, -13208, +13940; HincII: +12026, -12406, -13259, -13634; HinfI: +12925, -13031, -13103, -13268, -13916; Hpa I: -12406; Mbo I: +12528, +12629, +12795/12798/12806/13374, +12849, +13004/13018/13182/13194, +13104, +13152, +13180, +13367, +13575; Msp I: +13100, +14139; Rsa I: +12345, +12345/12350/12528, +12810, +13096, -13325, +13542; Taq I: -13404, +13635, +14050/14366 (Wallace et al., 1994). </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>11 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 LEBER OPTIC ATROPHY</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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MTND5, LHON13708A
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<br />
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SNP: rs28359178,
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ClinVar: RCV000010336, RCV000854970
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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>This allele changes the moderately conserved alanine at amino acid 458 to a threonine (A458T). This mutation does not in itself appear to cause LHON, but is present in about 30% of Caucasian patients as compared to 6% of random population controls. The mutation is generally associated with the primary LHON mutations MTND6*LHON14484A (516006.0001) and/or MTCYB*LHON15257A (516020.0001) and occasionally with the secondary LHON mutations MTND2*LHON5244A (516001.0002) and MTCYB*LHON15812A (516020.0002). (Brown et al., 1992; Johns and Berman, 1991; Johns et al., 1992; Johns and Neufeld, 1991). </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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<h4>
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<span class="mim-font">
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<strong>.0002 LEBER OPTIC ATROPHY</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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MTND5, LHON13730A
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<br />
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SNP: rs387906425,
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ClinVar: RCV000010337, RCV004595478
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a screening of bilateral optic atrophy patients who did not carry known primary LHON mutations, Howell et al. (1993) identified 1 patient with a transition mutation at nucleotide 13730 that resulted in the substitution of glutamic acid for glycine at position 465 of the ND5 protein. The patient was heteroplasmic for the mutation, which the authors believed was the primary event contributing to bilateral optic atrophy. Studies suggested that the mutation was of recent origin, probably within the germline of the patient's mother. The mutation was similar to the primary LHON mutation at nucleotide 14484 in the ND6 protein (516006.0001) in that it was weakly conserved and occurred within a hydrophobic region of the complex I region. Further, the patient with the 13730 mutation showed substantial recovery of vision, as do patients with the 14484 mutation. Howell et al. (1993) suggested that the screening of a broad range of optic atrophies would result in identification of additional primary or secondary LHON mutations. </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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<h4>
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<span class="mim-font">
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<strong>.0003 LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MTND5, 12706T-C, PHE124LEU
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<br />
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SNP: rs267606893,
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ClinVar: RCV000010338, RCV000144015, RCV002247308, RCV002260591
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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>Taylor et al. (2002) reported a 12706T-C transition in the MTND5 gene in a patient with Leigh syndrome (500017) and specific complex I deficiency (33% of control value in muscle mitochondria) (252010). The mutation was heteroplasmic (43% mutant load in skeletal muscle and 30% mutant load in skin fibroblasts) and changed an invariant amino acid (phe124 to leu) in a highly conserved transmembrane helix of the protein. The patient presented at age 6 years with optic atrophy. At age 20, he complained of leg weakness, and over the next several years he developed ataxia, facial weakness, impaired hearing, ophthalmoplegia, and weakness of the muscles of mastication, palate, and larynx. He died at age 24. Neuropathology revealed symmetrical foci of neuronal loss, gliosis and microcapillary proliferation in the putamen, periaqueductal gray matter, inferior olives, and cerebellar cortex. There was no family history, but the family declined further investigation. </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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<h4>
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<span class="mim-font">
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<strong>.0004 MELAS SYNDROME</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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MTND5, 12770A-G, GLU145GLY
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SNP: rs267606894,
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ClinVar: RCV000010339
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with MELAS syndrome (540000) characterized by focal neurologic dysfunction, increased CSF lactate, and abnormalities on MRI, Liolitsa et al. (2003) identified a heteroplasmic 12770A-G transition in the MTND5 gene, resulting in a glu145-to-gly (E145G) mutation. Skeletal muscle biopsy was normal, with no ragged-red fibers or COX-negative fibers. There was a 48% mutant load in muscle. </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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<h4>
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<span class="mim-font">
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<strong>.0005 MELAS SYNDROME</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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LEBER OPTIC ATROPHY, INCLUDED<br />
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LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY, INCLUDED
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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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MTND5, 13045A-C, MET237LEU
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<br />
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SNP: rs267606895,
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ClinVar: RCV000010340, RCV000010341, RCV000010342, RCV004791209
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with phenotypic overlap of MELAS syndrome (540000), Leber optic atrophy (535000), and Leigh syndrome (500017), Liolitsa et al. (2003) identified a heteroplasmic 13045A-C transversion in the MTND5 gene, resulting in a met237-to-leu (M237L) mutation. The patient had neurologic symptoms including migraine, ataxia, seizures, cognitive impairment, lesions on MRI, and ocular abnormalities. Muscle biopsy showed no ragged-red fibers or COX-negative fibers, and complex I activity was mildly reduced (252010). Mutant load was 82% in muscle. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MELAS SYNDROME, INCLUDED
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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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MTND5, 13084A-T, SER250CYS
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<br />
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SNP: rs267606896,
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ClinVar: RCV000010343, RCV000010344, RCV004791210
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with a progressive neurodegenerative disorder combining features of Leigh (500017) and MELAS (540000) syndromes, Crimi et al. (2003) identified a 13084A-T transversion in the MTND5 gene, resulting in a ser250-to-cys (S250C) substitution. Muscle biopsy revealed partial complex I deficiency (252010). The mutation was detected in a heteroplasmic state in the lymphocytes of the patient's mother (57%), who had migraine and optic atrophy, and younger sister (41%). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 MELAS SYNDROME</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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LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY, INCLUDED
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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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MTND5, 13513G-A, ASP393ASN
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<br />
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SNP: rs267606897,
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ClinVar: RCV000010345, RCV000010346, RCV000144016, RCV000224472, RCV000494941
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with MELAS syndrome (540000), Santorelli et al. (1997) identified a heteroplasmic 13513G-A transition in the MTND5 gene, resulting in an asp393-to-asn (D393N) substitution. </p><p>Kirby et al. (2003) identified the D393N mutation in 3 unrelated patients with Leigh syndrome (500017) and complex I deficiency (252010). The mutation was present in mutant loads of approximately 50% or less in all tissues tested, including multiple brain regions. The threshold mutant load for causing a complex I defect in cultured cells was approximately 30%. The findings suggested that the mutation causes a complex I defect when present at unusually low mutant loads and may act dominantly. </p><p>In 3 of 14 unrelated children with Leigh syndrome and complex I deficiency, Chol et al. (2003) identified the D393N mutation in the MTND5 gene. All 3 children had a peculiar MRI aspect distinct from typical Leigh syndrome: brain MRI consistently showed a specific involvement of the substantia nigra and medulla oblongata sparing the basal ganglia. The mutation, which affects an evolutionarily conserved amino acid, had previously been observed in adult patients with MELAS syndrome or an overlap of Leber hereditary optic neuropathy (LHON; 535000) and MELAS syndromes (Pulkes et al., 1999), emphasizing the clinical heterogeneity of mitochondrial DNA mutations. </p><p>Sudo et al. (2004) identified the D393N mutation in 6 of 84 (7%) Japanese patients with Leigh syndrome. The proportions of mutant mtDNA in muscles were relatively low (42 to 70%). The onset in patients with this mutation was delayed compared to those with the more common mutations at nucleotide 8993 in the MTATP6 gene (see 516060.0001 and 516060.0002), and ptosis and cardiac conduction abnormalities were frequently seen (83%). Sudo et al. (2004) suggested that the 13513G-A mutation is a frequent cause of Leigh syndrome and that patients with this mutation may have a characteristic clinical course. </p><p>In a clinical presentation case, Dickerson et al. (2005) discussed a patient with the MELAS syndrome due to the 13513G-A mutation who had onset of her illness in her early sixties, making her the oldest patient with this syndrome known to carry that specific mutation. The onset of the clinical manifestations consisted of seizures and altered mental status at the age of 61 years. Difficulty hearing began about 6 months later. The patient died about 2 years after onset. Dickerson et al. (2005) stated that among the 6 reported patients with the MELAS syndrome and the 13513G-A mutation, all had the clinical features of the disorder, including hearing loss, by their mid-forties, and most were in their second decade at onset. </p><p>Blok et al. (2007) reported 2 unrelated patients with oxidative phosphorylation defects associated with low levels of 13513G-A heteroplasmy. An 11-year-old girl presented with exercise intolerance and mild developmental delay. Brain MRI showed a subinsular cerebral infarct consistent with MELAS. She also had mild external ophthalmoplegia and strabismus. Skeletal muscle biopsy as an adult showed decreased complex I activity (58% of control). The mutation was present in blood (4 to 6%), fibroblasts (1 to 5%) and muscle (13 to 15%). A 5-month-old boy with a MELAS/Leigh phenotype showed failure to thrive, psychomotor retardation, retinitis pigmentosa, microcytic anemia, and characteristic brain lesions on MRI. He died at age 19 months after a viral infection. Skeletal muscle complex I activity was 8% of control; the mutation was present at 11 to 17% in blood, hair, and skeletal muscle. Blok et al. (2007) noted that low loads of MTND5 mutations can still result in a severe clinical phenotype because ND5 synthesis is probably the rate-limiting step for the activity of complex I. </p><p>Shanske et al. (2008) reported 12 patients with the 13513G-A mutation. The 3 adult patients had typical features of MELAS, whereas the other 9 infants and children had typical features of Leigh syndrome. Biochemical studies showed that complex I deficiency was inconsistent and generally mild, but mutation load in muscle and blood was relatively high. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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|
<strong>.0008 MELAS SYNDROME</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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MERRF SYNDROME, INCLUDED<br />
|
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LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY, INCLUDED
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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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MTND5, 13042G-A, ALA236THR
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<br />
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SNP: rs267606898,
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ClinVar: RCV000010347, RCV000010348, RCV000010349, RCV000854885, RCV002260592
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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 25-year-old man with MELAS syndrome (540000), Naini et al. (2005) identified a heteroplasmic 13042G-A transition in the MTND5 gene, resulting in an ala236-to-thr (A236T) substitution. The patient had normal psychomotor development until age 17 years, when he had a tonic-clonic seizure. At age 20 years, he had a severe stroke necessitating prolonged rehabilitation. In the following years, he experienced more stroke-like episodes, partial seizures, memory loss, migraine-like headaches, myoclonus, exercise intolerance, and osteoporosis with vertebral fracture. Naini et al. (2005) noted the similarities to MERRF syndrome (545000), although there were no ragged-red fibers on muscle biopsy. Muscle biopsy showed decreased activity of complex I. The mutation was heteroplasmic in both muscle (90%) and blood (50%). The patient's mother reportedly had multiple strokes and seizures since her thirties, as well as migraine headaches and mild hearing loss. She did not have myoclonus. </p><p>Blok et al. (2007) reported a boy with a Leigh-like syndrome (500017) who was heteroplasmic for the 13042G-A mutation, which was identified in blood (77%), muscle (84%), and fibroblasts (86%). He presented at age 3 years with ataxia, internuclear ophthalmoplegia, increased serum and CSF lactate, and hyperintensities in the pons and midbrain. Skeletal muscle histology was normal. The patient's unaffected mother and grandmother also carried the mutation at much lower levels (2 to 25% in various tissues). </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>.0009 LEBER OPTIC ATROPHY</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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MTND5, 12848C-T, ALA171VAL
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<br />
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SNP: rs267606899,
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ClinVar: RCV000010350
|
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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 man with Leber optic atrophy (535000) with onset at age 20 years, Mayorov et al. (2005) identified a heteroplasmic 12848C-T transition in a highly conserved region of the MTND5 gene, resulting in an ala171-to-val (A171V) substitution. Lymphoblasts derived from the proband contained 54% mutant mtDNA, whereas lymphoblasts from his unaffected mother contained 37% mutant mtDNA. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 PARKINSON DISEASE 6, MODIFIER OF</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
|
MTND5, 12397A-G
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<br />
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|
|
SNP: rs1556424100,
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|
|
|
ClinVar: RCV000010351, RCV000854803
|
|
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a patient with early-onset Parkinson disease (PARK6; 605909) due to a homozygous mutation in the PINK1 gene (608309.0002), Piccoli et al. (2008) identified a homoplasmic 12397A-G mutation in the MTND5 gene and a homoplasmic mutation in the MTND6 gene (516006.0008). The 12397A-G mutation results in a thr21-to-ala (T21A) substitution in a hydrophilic segment that is likely exposed to the intermembrane mitochondrial space. The patient had onset at age 22 years. His mother, who was heterozygous for the PINK1 mutation, was also homoplasmic for both mitochondrial mutations and showed disease onset at age 53. The father, who was heterozygous for the PINK1 mutation only, was unaffected at age 79. Biochemical studies of the proband's fibroblasts showed mitochondrial dysfunction, with decreased amounts of cytochrome c oxidase, impaired complex I activity, and increased hydrogen peroxide generation. Piccoli et al. (2008) concluded that the presence of the mitochondrial mutations in combination with the PINK1 mutation may have accelerated the onset of the disease. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 LEBER OPTIC ATROPHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
MTND5, 12338T-C, MET1THR
|
|
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|
|
<br />
|
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|
|
SNP: rs201863060,
|
|
|
|
|
|
|
|
ClinVar: RCV000022893, RCV000854787
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Liu et al. (2011) investigated the molecular pathogenesis of LHON (535000) in 6 Han Chinese families in which 9 (6 males/3 females) of 86 matrilineal relatives exhibited variable severity and age of onset of optic neuropathy. The average age of onset was 20 years and the penetrance of visual impairment averaged 10.8%. Molecular analysis of mtDNA in these families identified the homoplasmic ND5 12338T-C mutation and a distinct set of variants belonging to the Asian haplogroup F2. The mutation resulted in the replacement of the first amino acid, translation-initiating methionine with a threonine (M1T). This methionine in ND5 is an extraordinarily conserved residue from bacteria to human mitochondria. The 12338T-C mutation was present in the maternal lineage of the 6 pedigrees and not in 178 Chinese controls. </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>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Brown et al. (1992); Montoya et al. (1981)
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</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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Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., Schreier, P. H., Smith, A. J. H., Staden, R., Young, I. G.
|
|
<strong>Sequence and organization of the human mitochondrial genome.</strong>
|
|
Nature 290: 457-465, 1981.
|
|
|
|
|
|
[PubMed: 7219534]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/290457a0]
|
|
|
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</p>
|
|
</li>
|
|
|
|
<li>
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<p class="mim-text-font">
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Arizmendi, J. M., Skehel, J. M., Runswick, M. J., Fearnley, I. M., Walker, J. E.
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<strong>Complementary DNA sequences of two 14.5 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Complementation of the primary structure of the complex.</strong>
|
|
FEBS Lett. 313: 80-84, 1992.
|
|
|
|
|
|
[PubMed: 1426273]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0014-5793(92)81189-s]
|
|
|
|
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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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Attardi, G., Chomyn, A., Doolittle, R. F., Mariottini, P., Ragan, C. I.
|
|
<strong>Seven unidentified reading frames of human mitochondrial DNA encode subunits of the respiratory chain NADH dehydrogenase.</strong>
|
|
Cold Spring Harbor Symp. Quant. Biol. 51: 103-114, 1986.
|
|
|
|
|
|
[PubMed: 3472707]
|
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|
|
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|
[Full Text: https://doi.org/10.1101/sqb.1986.051.01.013]
|
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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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Attardi, G., Chomyn, A., Montoya, J., Ojala, D.
|
|
<strong>Identification and mapping of human mitochondrial genes.</strong>
|
|
Cytogenet. Cell Genet. 32: 85-98, 1982.
|
|
|
|
|
|
[PubMed: 7140372]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000131689]
|
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|
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Blok, M. J., Spruijt, L., de Coo, I. F. M., Schoonderwoerd, K., Hendrickx, A., Smeets, H. J.
|
|
<strong>Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease.</strong>
|
|
J. Med. Genet. 44: e74, 2007. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 17400793]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2006.045716]
|
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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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Brown, M. D., Voljavec, A. S., Lott, M. T., MacDonald, I., Wallace, D. C.
|
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<strong>Leber's hereditary optic neuropathy; a model for mitochondrial neurodegenerative diseases.</strong>
|
|
FASEB J. 6: 2791-2799, 1992.
|
|
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|
|
|
[PubMed: 1634041]
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|
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|
[Full Text: https://doi.org/10.1096/fasebj.6.10.1634041]
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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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Brown, M. D., Voljavec, A. S., Lott, M. T., Torroni, A., Yang, C.-C., Wallace, D. C.
|
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<strong>Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.</strong>
|
|
Genetics 130: 163-173, 1992.
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|
[PubMed: 1732158]
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[Full Text: https://doi.org/10.1093/genetics/130.1.163]
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</p>
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</li>
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|
<li>
|
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<p class="mim-text-font">
|
|
Case, J. T., Wallace, D. C.
|
|
<strong>Maternal inheritance of mitochondrial DNA polymorphisms in cultured human fibroblasts.</strong>
|
|
Somat. Cell Genet. 7: 103-108, 1981.
|
|
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|
|
[PubMed: 6261411]
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|
|
|
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|
[Full Text: https://doi.org/10.1007/BF01544751]
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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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Chol, M., Lebon, S., Benit, P., Chretien, D., de Lonlay, P., Goldenberg, A., Odent, S., Hertz-Pannier, L., Vincent-Delorme, C., Cormier-Daire, V., Rustin, P., Rotig, A., Munnich, A.
|
|
<strong>The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency.</strong>
|
|
J. Med. Genet. 40: 188-191, 2003.
|
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|
[PubMed: 12624137]
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[Full Text: https://doi.org/10.1136/jmg.40.3.188]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Chomyn, A., Cleeter, W. J., Ragan, C. I., Riley, M., Doolittle, R. F., Attardi, G.
|
|
<strong>URF6, last unidentified reading frame of human mtDNA, codes for an NADH dehydrogenase subunit.</strong>
|
|
Science 234: 614-618, 1986.
|
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|
[PubMed: 3764430]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.3764430]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chomyn, A., Mariottini, P., Cleeter, M. W. J., Ragan, C. I., Matsuno-Yagi, A., Hatefi, Y., Doolittle, R. G., Attardi, G.
|
|
<strong>Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase.</strong>
|
|
Nature 314: 592-597, 1985.
|
|
|
|
|
|
[PubMed: 3921850]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/314592a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crimi, M., Galbiati, S., Moroni, I., Bordoni, A., Perini, M. P., Lamantea, E., Sciacco, M., Zeviani, M., Biunno, I., Moggio, M., Scarlato, G., Comi, G. P.
|
|
<strong>A missense mutation in the mitochondrial ND5 gene associated with a Leigh-MELAS overlap syndrome.</strong>
|
|
Neurology 60: 1857-1861, 2003.
|
|
|
|
|
|
[PubMed: 12796552]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000066048.72780.69]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dickerson, B. C., Holtzman, D., Grant, P. E., Tian, D.
|
|
<strong>Case 36-2005: a 61-year-old woman with seizure, disturbed gait, and altered mental status.</strong>
|
|
New Eng. J. Med. 353: 2271-2280, 2005.
|
|
|
|
|
|
[PubMed: 16306525]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMcpc059032]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giles, R. E., Blanc, H., Cann, H. M., Wallace, D. C.
|
|
<strong>Maternal inheritance of human mitochondrial DNA.</strong>
|
|
Proc. Nat. Acad. Sci. 77: 6715-6719, 1980.
|
|
|
|
|
|
[PubMed: 6256757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.77.11.6715]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Howell, N., Halvorson, S., Burns, J., McCullough, D. A., Poulton, J.
|
|
<strong>When does bilateral optic atrophy become Leber hereditary optic neuropathy? (Letter)</strong>
|
|
Am. J. Hum. Genet. 53: 959-963, 1993.
|
|
|
|
|
|
[PubMed: 8213825]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Berman, J.
|
|
<strong>Alternative, simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic atrophy.</strong>
|
|
Biochem. Biophys. Res. Commun. 174: 1324-1330, 1991.
|
|
|
|
|
|
[PubMed: 1900003]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(91)91567-v]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Neufeld, M. J., Park, R. D.
|
|
<strong>An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy.</strong>
|
|
Biochem. Biophys. Res. Commun. 187: 1551-1557, 1992.
|
|
|
|
|
|
[PubMed: 1417830]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(92)90479-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johns, D. R., Neufeld, M. J.
|
|
<strong>Cytochrome b mutations in Leber hereditary optic neuropathy.</strong>
|
|
Biochem. Biophys. Res. Commun. 181: 1358-1364, 1991.
|
|
|
|
|
|
[PubMed: 1764087]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(91)92088-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kirby, D. M., Boneh, A., Chow, C. W., Ohtake, A., Ryan, M. T., Thyagarajan, D., Thorburn, D. R.
|
|
<strong>Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease.</strong>
|
|
Ann. Neurol. 54: 473-478, 2003.
|
|
|
|
|
|
[PubMed: 14520659]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.10687]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liolitsa, D., Rahman, S., Benton, S., Carr, L. J., Hanna, M. G.
|
|
<strong>Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations?</strong>
|
|
Ann. Neurol. 53: 128-132, 2003.
|
|
|
|
|
|
[PubMed: 12509858]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.10435]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liu, X.-L., Zhou, X., Zhou, J., Zhao, F., Zhang, J., Li, C., Ji, Y., Zhang, Y., Wei, Q.-P., Sun, Y.-H., Yang, L., Lin, B., Yuan, Y., Li, Y., Qu, J., Guan, M.-X.
|
|
<strong>Leber's hereditary optic neuropathy is associated with the T12338C mutation in mitochondrial ND5 gene in six Han Chinese families.</strong>
|
|
Ophthalmology 118: 978-985, 2011.
|
|
|
|
|
|
[PubMed: 21131053]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ophtha.2010.09.003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mayorov, V., Biousse, V., Newman, N. J., Brown, M. D.
|
|
<strong>The role of the ND5 gene in LHON: characterization of a new, heteroplasmic LHON mutation.</strong>
|
|
Ann. Neurol. 58: 807-811, 2005.
|
|
|
|
|
|
[PubMed: 16240359]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20669]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montoya, J., Ojala, D., Attardi, G.
|
|
<strong>Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs.</strong>
|
|
Nature 290: 465-470, 1981.
|
|
|
|
|
|
[PubMed: 7219535]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/290465a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Naini, A. B., Lu, J., Kaufmann, P., Bernstein, R. A., Mancuso, M., Bonilla, E., Hirano, M., DiMauro, S.
|
|
<strong>Novel mitochondrial DNA ND5 mutation in a patient with clinical features of MELAS and MERRF.</strong>
|
|
Arch. Neurol. 62: 473-476, 2005.
|
|
|
|
|
|
[PubMed: 15767514]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.62.3.473]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nishigaki, Y., Marti, R., Hirano, M.
|
|
<strong>ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy.</strong>
|
|
Hum. Molec. Genet. 13: 91-101, 2004.
|
|
|
|
|
|
[PubMed: 14613972]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh010]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ojala, D., Montoya, J., Attardi, G.
|
|
<strong>tRNA punctuation model of RNA processing in human mitochondria.</strong>
|
|
Nature 290: 470-474, 1981.
|
|
|
|
|
|
[PubMed: 7219536]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/290470a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., McCarthy, J., Wallace, D. C.
|
|
<strong>Comparison of mitochondrially synthesized polypeptides of human, mouse, and monkey cell lines by a two-dimensional protease gel system.</strong>
|
|
Somat. Cell Molec. Genet. 10: 639-643, 1984.
|
|
|
|
|
|
[PubMed: 6438810]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01535230]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oliver, N. A., Wallace, D. C.
|
|
<strong>Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction.</strong>
|
|
Molec. Cell. Biol. 2: 30-41, 1982.
|
|
|
|
|
|
[PubMed: 6955589]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.2.1.30-41.1982]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Park, J. S., Sharma, L. K., Li, H., Xiang, R., Holstein, D., Wu, J., Lechleiter, J., Naylor, S. L., Deng, J. J., Lu, J., Bai, Y.
|
|
<strong>A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis.</strong>
|
|
Hum. Molec. Genet. 18: 1578-1589, 2009.
|
|
|
|
|
|
[PubMed: 19208652]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp069]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Piccoli, C., Ripoli, M., Quarato, G., Scrima, R., D'Aprile, A., Boffoli, D., Margaglione, M., Criscuolo, C., De Michele, G., Sardanelli, A., Papa, S., Capitanio, N.
|
|
<strong>Coexistence of mutations in PINK1 and mitochondrial DNA in early onset parkinsonism. (Letter)</strong>
|
|
J. Med. Genet. 45: 596-602, 2008.
|
|
|
|
|
|
[PubMed: 18524835]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2008.058628]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pulkes, T., Eunson, L., Patterson, V., Siddiqui, A., Wood, N. W., Nelson, I. P., Morgan-Hughes, J. A., Hanna, M. G.
|
|
<strong>The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS.</strong>
|
|
Ann. Neurol. 46: 916-919, 1999. Note: Erratum: Ann. Neurol. 47: 841 only, 2000.
|
|
|
|
|
|
[PubMed: 10589546]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1531-8249(199912)46:6<916::aid-ana16>3.0.co;2-r]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ragan, C. I.
|
|
<strong>Structure of NADH-ubiquinone reductase (complex I).</strong>
|
|
Curr. Top. Bioenerg. 15: 1-36, 1987.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Safra, M., Sas-Chen, A., Nir, R., Winkler, R., Nachshon, A., Bar-Yaacov, D., Erlacher, M., Rossmanith, W., Stern-Ginossar, N., Schwartz, S.
|
|
<strong>The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution.</strong>
|
|
Nature 551: 251-255, 2017.
|
|
|
|
|
|
[PubMed: 29072297]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature24456]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Santorelli, F. M., Tanji, K., Kulikova, R., Shanske, S., Vilarinho, L., Hays, A. P., DiMauro, S.
|
|
<strong>Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS.</strong>
|
|
Biochem. Biophys. Res. Commun. 238: 326-328, 1997.
|
|
|
|
|
|
[PubMed: 9299505]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1997.7167]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shanske, S., Coku, J., Lu, J., Ganesh, J., Krishna, S., Tanji, K., Bonilla, E., Naini, A. B., Hirano, M., DiMauro, S.
|
|
<strong>The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome.</strong>
|
|
Arch. Neurol. 65: 368-372, 2008.
|
|
|
|
|
|
[PubMed: 18332249]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneurol.2007.67]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shoffner, J. M., Wallace, D. C.
|
|
<strong>Oxidative phosphorylation diseases.In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. Vol. 1.</strong>
|
|
New York: McGraw-Hill (pub.) 1995. Pp. 1535-1609.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sudo, A., Honzawa, S., Nonaka, I., Goto, Y.
|
|
<strong>Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and clinical features in Japan.</strong>
|
|
J. Hum. Genet. 49: 92-96, 2004.
|
|
|
|
|
|
[PubMed: 14730434]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-003-0116-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, R. W., Morris, A. A. M., Hutchinson, M., Turnbull, D. M.
|
|
<strong>Leigh disease associated with a novel mitochondrial DNA ND5 mutation.</strong>
|
|
Europ. J. Hum. Genet. 10: 141-144, 2002.
|
|
|
|
|
|
[PubMed: 11938446]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200773]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Walker, J. E., Arizmendi, J. M., Dupuis, A., Fearnley, I. M., Finel, M., Medd, S. M., Pilkington, S. J., Runswick, M. J., Skehel, J. M.
|
|
<strong>Sequences of 20 subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Application of a novel strategy for sequencing proteins using the polymerase chain reaction.</strong>
|
|
J. Molec. Biol. 226: 1051, 1992.
|
|
|
|
|
|
[PubMed: 1518044]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0022-2836(92)91052-q]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Lott, M. T., Torroni, A., Brown, M. D., Shoffner, J. M.
|
|
<strong>Report of the Committee on human mitochondrial DNA.In: Cuticchia, A. J.; Pearson, P. L. (eds.) : Human Gene Mapping, 1993: A Compendium.</strong>
|
|
Baltimore: Johns Hopkins Univ. Press (pub.) 1994. Pp. 813-845.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Yang, J., Ye, J., Lott, M. T., Oliver, N. A., McCarthy, J.
|
|
<strong>Computer prediction of peptide maps: Assignment of polypeptides to human and mouse mitochondrial DNA genes by analysis of two-dimensional-proteolytic digest gels.</strong>
|
|
Am. J. Hum. Genet. 38: 461, 1986.
|
|
|
|
|
|
[PubMed: 3518425]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
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|
|
</div>
|
|
|
|
</div>
|
|
|
|
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|
|
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|
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|
|
|
|
|
|
|
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|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 02/08/2018<br>Jane Kelly - updated : 8/26/2011<br>George E. Tiller - updated : 10/15/2009<br>Cassandra L. Kniffin - updated : 1/12/2009<br>Cassandra L. Kniffin - updated : 10/6/2008<br>Cassandra L. Kniffin - updated : 5/30/2007<br>Cassandra L. Kniffin - updated : 3/31/2006<br>George E. Tiller - updated : 3/7/2006<br>Victor A. McKusick - updated : 2/16/2006<br>Cassandra L. Kniffin - updated : 6/27/2005<br>Marla J. F. O'Neill - updated : 3/18/2004<br>Victor A. McKusick - updated : 3/1/2004<br>Cassandra L. Kniffin - updated : 1/7/2004<br>Cassandra L. Kniffin - updated : 8/11/2003<br>Cassandra L. Kniffin - updated : 3/6/2003<br>Michael B. Petersen - updated : 10/22/2002<br>Jane Kelly - updated : 4/2/2002<br>Douglas C. Wallace - updated : 4/6/1994
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|
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|
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|
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|
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carol : 05/20/2024<br>carol : 05/15/2024<br>carol : 02/09/2018<br>alopez : 02/08/2018<br>carol : 07/08/2016<br>carol : 8/30/2011<br>terry : 8/26/2011<br>terry : 5/24/2011<br>terry : 11/3/2010<br>carol : 1/19/2010<br>wwang : 10/20/2009<br>terry : 10/15/2009<br>wwang : 8/21/2009<br>wwang : 1/20/2009<br>ckniffin : 1/12/2009<br>wwang : 10/7/2008<br>ckniffin : 10/6/2008<br>terry : 8/26/2008<br>terry : 8/26/2008<br>wwang : 6/6/2007<br>ckniffin : 5/30/2007<br>wwang : 4/6/2006<br>ckniffin : 3/31/2006<br>wwang : 3/7/2006<br>alopez : 3/6/2006<br>terry : 2/16/2006<br>carol : 9/21/2005<br>ckniffin : 8/29/2005<br>wwang : 7/14/2005<br>wwang : 7/13/2005<br>ckniffin : 6/27/2005<br>tkritzer : 3/22/2004<br>tkritzer : 3/18/2004<br>tkritzer : 3/2/2004<br>terry : 3/1/2004<br>tkritzer : 1/14/2004<br>ckniffin : 1/7/2004<br>tkritzer : 8/19/2003<br>ckniffin : 8/11/2003<br>ckniffin : 8/11/2003<br>tkritzer : 4/8/2003<br>tkritzer : 4/8/2003<br>ckniffin : 3/6/2003<br>ckniffin : 3/6/2003<br>carol : 10/22/2002<br>cwells : 4/2/2002<br>joanna : 9/17/2001<br>dkim : 12/15/1998<br>dholmes : 5/11/1998<br>dholmes : 5/11/1998<br>terry : 1/21/1997<br>mark : 4/9/1996<br>mimman : 2/8/1996<br>mark : 6/19/1995<br>pfoster : 8/16/1994<br>mimadm : 5/17/1994<br>carol : 2/28/1994<br>carol : 10/11/1993
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