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Entry
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- *601465 - DEOXYGUANOSINE KINASE; DGUOK
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*601465</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/601465">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000114956;t=ENST00000264093" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=1716" 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=601465" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000114956;t=ENST00000264093" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001318859,NM_001318860,NM_001318861,NM_001318862,NM_001318863,NM_080916,NM_080918,NR_134893,NR_134894,NR_134895,NR_134896,NR_134897,NR_134898,XM_011532647,XM_047443585,XM_047443587" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_080916" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=601465" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=03273&isoform_id=03273_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/DGUOK" 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/1477482,1763976,1871164,16041753,18426967,18426971,18645174,23503050,33876021,62630165,119620110,119620112,119620115,119620116,119620117,311349458,311349459,311349461,311349462,311349464,311349465,311349467,311349468,311349470,311349471,311349473,311349474,311349476,311349477,311349479,311349480,311349482,311349483,311349485,311349486,311349488,311349489,311349491,311349492,311349494,311349495,311349497,311349498,311349500,311349501,311349503,311349504,311349506,311349507,311349509,311349510,311349512,311349513,311349515,311349516,311349518,311349519,311349521,311349522,311349524,311349525,311349527,311349528,311349530,311349531,311349533,311349534,311349536,311349537,311349539,311349540,311349542,311349543,311349545,311349546,311349548,311349549,311349551,311349552,311349554,311349555,311349557,311349558,311349560,311349561,311349563,311349564,311349566,311349567,311349569,311349570,311349572,311349573,311349575,311349576,767914050,957949264,957949267,957949270,974005410,974005412,974005414,974005416,974005418,2217326156,2217326158,2462570834,2462570836,2462570838" 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/Q16854" 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=1716" 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=ENSG00000114956;t=ENST00000264093" 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=DGUOK" 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=DGUOK" 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+1716" 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/DGUOK" 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:1716" 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/1716" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr2&hgg_gene=ENST00000264093.9&hgg_start=73926880&hgg_end=73958946&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:2858" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2858" 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/dguok" 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=601465[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=601465[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000114956" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=DGUOK" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=DGUOK" 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=DGUOK" 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=DGUOK&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/PA27319" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:2858" 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://www.mousephenotype.org/data/genes/MGI:1351602" 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/DGUOK#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:1351602" 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/1716/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=1716" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040625-14" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1716" 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=DGUOK&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 783734000<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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601465
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
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<span class="mim-font">
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DEOXYGUANOSINE KINASE; DGUOK
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
DEOXYGUANOSINE KINASE, MITOCHONDRIAL; DGK
|
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</span>
|
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</h4>
|
|
</div>
|
|
</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DGUOK" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DGUOK</a></em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/2/371?start=-3&limit=10&highlight=371">2p13.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:73926880-73958946&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">2:73,926,880-73,958,946</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=251880,617068,617070" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/371?start=-3&limit=10&highlight=371">
|
|
2p13.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/251880"> 251880 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
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|
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</tr>
|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Portal hypertension, noncirrhotic, 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617068"> 617068 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
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Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4
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<p>Purine deoxyribonucleoside analogs are extensively used in treatment of lymphoproliferative disorders. These compounds are administered as pro-drugs, and their efficiency is dependent on intracellular phosphorylation to the corresponding triphosphates. In mammalian cells, the phosphorylation of purine deoxyribonucleosides is mediated predominantly by 2 deoxyribonucleoside kinases: cytosolic deoxycytidine kinase (DCK; <a href="https://enzyme.expasy.org/EC/2.7.1.74" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.1.74</a>; <a href="/entry/125450">125450</a>) and mitochondrial deoxyguanosine kinase (DGK; <a href="https://enzyme.expasy.org/EC/2.7.1.113" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.1.113</a>).</p>
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<p><a href="#2" class="mim-tip-reference" title="Johansson, M., Karlsson, A. <strong>Cloning and expression of human deoxyguanosine kinase cDNA.</strong> Proc. Nat. Acad. Sci. 93: 7258-7262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8692979/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8692979</a>] [<a href="https://doi.org/10.1073/pnas.93.14.7258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8692979">Johansson and Karlsson (1996)</a> used the human DCK cDNA sequence to find homologous cDNA sequences in an attempt to identify novel DCK-related enzymes. Several cDNA clones with 40 to 50% DNA sequence identity to human DCK were found in the GenBank sequence database, and the cDNA with the longest open reading frame was expressed in Escherichia coli. The protein was found to have the same substrate specificity as purified native DGK. Furthermore, the N-terminal sequence contained a possible mitochondrial translocation signal. <a href="#2" class="mim-tip-reference" title="Johansson, M., Karlsson, A. <strong>Cloning and expression of human deoxyguanosine kinase cDNA.</strong> Proc. Nat. Acad. Sci. 93: 7258-7262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8692979/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8692979</a>] [<a href="https://doi.org/10.1073/pnas.93.14.7258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8692979">Johansson and Karlsson (1996)</a> suggested that DCK may be present only in the cytosol and DGK only in mitochondria. The presumed mitochondrial translocation signal would be removed by cleavage at a putative mitochondrial peptidase cleavage site to give a mature protein size of 28 kD. Northern blot analysis detected a 1.3-kb DGK transcript with no cross-hybridization to the 2.8-kb DCK mRNA. DGK mRNA was detected in all tissues investigated with the highest expression levels in muscle, brain, liver, and lymphoid tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8692979" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Mitochondrial DNA Depletion Syndrome 3 (Hepatocerebral Type)</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N. <strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong> Nature Genet. 29: 337-341, 2001. Note: Erratum: Nature Genet. 29: 491 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687800</a>] [<a href="https://doi.org/10.1038/ng746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11687800">Mandel et al. (2001)</a> used homozygosity mapping in 3 kindreds of Druze origin to map a hepatocerebral type of mitochondrial DNA depletion syndrome (MTDPS3; <a href="/entry/251880">251880</a>) to a region of 6.1 cM on chromosome 2p13. This interval encompasses the DGUOK gene. They identified a 1-bp deletion (<a href="#0001">601465.0001</a>) within the DGUOK gene that segregated with the disease in the 3 kindreds studied. Affected individuals had early onset of progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion. Western blot analysis failed to detect DGK protein in the liver of affected persons. The main supply of deoxyribonucleotides (dNTPs) for mtDNA synthesis comes from the salvage pathway initiated by DGK and thymidine kinase-2 (TK2; <a href="/entry/188250">188250</a>). The association of mtDNA depletion with mutated DGUOK suggested that the salvage pathway enzymes are involved in the maintenance of balanced mitochondrial dNTP pools. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Taanman, J.-W., Muddle, J. R., Muntau, A. C. <strong>Mitochondrial DNA depletion can be prevented by dGMP and dAMP supplementation in a resting culture of deoxyguanosine kinase-deficient fibroblasts.</strong> Hum. Molec. Genet. 12: 1839-1845, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12874104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12874104</a>] [<a href="https://doi.org/10.1093/hmg/ddg192" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12874104">Taanman et al. (2003)</a> studied fibroblasts from a patient described by <a href="#8" class="mim-tip-reference" title="Taanman, J.-W., Kateeb, I., Muntau, A. C., Jaksch, M., Cohen, N., Mandel, H. <strong>A novel mutation in the deoxyguanosine kinase gene causing depletion of mitochondrial DNA.</strong> Ann. Neurol. 52: 237-239, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210798</a>] [<a href="https://doi.org/10.1002/ana.10247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12210798">Taanman et al. (2002)</a> who was homozygous for an arg105-to-ter substitution in the DGUOK gene (R105X; <a href="#0002">601465.0002</a>). Although mtDNA synthesis was cell cycle-independent in control fibroblasts, mtDNA synthesis occurred mainly during the S-phase in deoxyguanosine kinase-deficient cells. Consistent with this observation, the mtDNA content of exponentially growing, deoxyguanosine kinase-deficient cells was only mildly affected. When cycling was inhibited by serum deprivation and cells were in a resting state, however, the mtDNA content dropped considerably in deoxyguanosine kinase-deficient cells, yet remained stable in control fibroblasts. The decline in mtDNA content in resting, deoxyguanosine kinase-deficient cells could be prevented by deoxyguanosine monophosphate (DGMP) and deoxyadenosine monophosphate (dAMP) supplementation, providing conclusive evidence that substrate limitation triggers mtDNA depletion in deoxyguanosine kinase-deficient cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12210798+12874104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Tadiboyina, V. T., Rupar, A., Atkison, P. Feigenbaum, A., Kronick, J., Wang, J., Hegele, R. A. <strong>Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria.</strong> Am. J. Med. Genet. 135A: 289-291, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15887277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15887277</a>] [<a href="https://doi.org/10.1002/ajmg.a.30748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15887277">Tadiboyina et al. (2005)</a> reported 3 patients with the hepatocerebral form of mtDNA depletion syndrome associated with cystathioninuria. All 3 children were homozygous for a mutation in the DGUOK gene (D255Y; <a href="#0007">601465.0007</a>), but had no mutations in the cystathionine gamma-lyase gene (CTH; <a href="/entry/607657">607657</a>), indicating that the hepatocerebral form of mtDNA depletion syndrome might be associated with secondary cystathioninuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15887277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Autosomal Recessive Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions 4</em></strong></p><p>
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In 6 patients, including 2 sibs, with adult-onset autosomal recessive progressive external ophthalmoplegia-4 (PEOB4; <a href="/entry/617070">617070</a>), <a href="#5" class="mim-tip-reference" title="Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M. <strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong> Brain 135: 3404-3415, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23043144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23043144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23043144[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/brain/aws258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23043144">Ronchi et al. (2012)</a> identified compound heterozygous mutations in the DGUOK gene (<a href="#0008">601465.0008</a>; <a href="#0010">601465.0010</a>-<a href="#0015">601465.0015</a>). One of the patients also had features of MTDPS3. The mutations, which were found by targeted exome sequencing and confirmed by standard sequencing, included both missense and truncating mutations. Skeletal muscle from patients showed mtDNA deletions as well as decreased protein levels and activity of DGUOK. The findings expanded the phenotype associated with DGUOK mutations. In this study, DGUOK mutations accounted for 5.6% of 90 probands with mtDNA deletions in skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23043144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Noncirrhotic Portal Hypertension 1</em></strong></p><p>
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In 3 patients from 2 unrelated consanguineous Turkish families with noncirrhotic portal hypertension-1 (NCPH1; <a href="/entry/617068">617068</a>), <a href="#11" class="mim-tip-reference" title="Vilarinho, S., Sari, S., Yilmaz, G., Stiegler, A. L., Boggon, T. J., Jain, D., Akyol, G., Dalgic, B., Gunel, M., Lifton, R. P. <strong>Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.</strong> Hepatology 63: 1977-1986, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26874653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26874653</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26874653[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/10.1002/hep.28499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26874653">Vilarinho et al. (2016)</a> identified a homozygous missense mutation in the DGUOK gene (N46S; <a href="#0008">601465.0008</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26874653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Zhou, X., Curbo, S., Zhao, Q., Krishnan, S., Kuiper, R., Karlsson, A. <strong>Severe mtDNA depletion and dependency on catabolic lipid metabolism in DGUOK knockout mice.</strong> Hum. Molec. Genet. 28: 2874-2884, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31127938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31127938</a>] [<a href="https://doi.org/10.1093/hmg/ddz103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31127938">Zhou et al. (2019)</a> found that Dguok -/- mice appeared normal at birth but began to lose weight at week 6, with decreased adipose tissue and significantly higher relative weights of liver, kidney, and heart at week 8. Fur color changed from black to blueish gray beginning at week 16, with completion at week 20. Liver, brain, heart, and skeletal muscle of Dguok -/- mice showed mitochondrial DNA (mtDNA) deficiency, with liver most severely affected. Liver mitochondrial ultrastructure was abnormal, with decreased expression of mtDNA-encoded CoxI (MTCO1; <a href="/entry/516030">516030</a>) and Nd1 (MTND1; <a href="/entry/516000">516000</a>). Mitochondrial dysfunction led to liver damage, decreased subcutaneous fat, and accumulation of lipofuscin in liver tissue with increased oxidative stress. Microarray analysis of liver tissue revealed increased catabolic lipid metabolism and upregulation of the de novo dNTP pathway in Dguok -/- mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31127938" 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>.0001 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886037613 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037613;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=rs886037613" 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=rs886037613" 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=RCV000008631 OR RCV000726828" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000008631, RCV000726828" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000008631...</a>
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<p>In affected members of 3 unrelated Israeli-Druze families with mitochondrial DNA depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>), manifest with hepatic and cerebral involvement, <a href="#3" class="mim-tip-reference" title="Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N. <strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong> Nature Genet. 29: 337-341, 2001. Note: Erratum: Nature Genet. 29: 491 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687800</a>] [<a href="https://doi.org/10.1038/ng746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11687800">Mandel et al. (2001)</a> identified a homozygous 1-bp deletion (204delA) in the DGUOK gene, predicted to result in a frameshift and premature termination at codon 80. All parents carried the mutation, and unaffected sibs were either carriers or homozygous with respect to the wildtype allele. There were 19 affected members in the 3 kindreds. Death usually occurred before 1 year of age. Enzymatic activities of the mitochondrial respiratory chain complexes containing mtDNA-encoded subunits (complexes I, III, and IV) were reduced to various extents, whereas complex II enzymatic activity, which is encoded solely by nuclear genes, was normal. Muscle tissue from 7 affected patients showed normal histology and respiratory chain complex activities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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DGUOK, ARG105TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893630 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893630;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104893630?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893630" 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=rs104893630" 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=RCV000008632 OR RCV002512916" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000008632, RCV002512916" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000008632...</a>
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<p>In 2 German brothers with mitochondrial DNA-depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>) characterized by lactic acidosis, hepatomegaly, hypoglycemia, jaundice, and encephalopathy with hypotonia, hyperreflexia, and nystagmus, <a href="#8" class="mim-tip-reference" title="Taanman, J.-W., Kateeb, I., Muntau, A. C., Jaksch, M., Cohen, N., Mandel, H. <strong>A novel mutation in the deoxyguanosine kinase gene causing depletion of mitochondrial DNA.</strong> Ann. Neurol. 52: 237-239, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210798</a>] [<a href="https://doi.org/10.1002/ana.10247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12210798">Taanman et al. (2002)</a> identified a homozygous 313C-T transition in exon 3 of the DGUOK gene, resulting in an arg105-to-ter (R105X) substitution, and a 173-amino acid truncation at the C terminus of the protein product. The unaffected parents were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12210798" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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DGUOK, 4-BP DUP, 763GATT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs763706988 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs763706988;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs763706988?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs763706988" 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=rs763706988" 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=RCV000008633 OR RCV000485369 OR RCV004528095 OR RCV005025033" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000008633, RCV000485369, RCV004528095, RCV005025033" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000008633...</a>
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<p>In a patient with mitochondrial DNA depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>), <a href="#6" class="mim-tip-reference" title="Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camano, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C. M., Feigenbaum, A., Naini, A. B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T. H. <strong>Mitochondrial DNA depletion and dGK gene mutations.</strong> Ann. Neurol. 52: 311-316, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205643</a>] [<a href="https://doi.org/10.1002/ana.10284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12205643">Salviati et al. (2002)</a> identified a homozygous 4-bp duplication (GATT) at nucleotide 763 in the DGUOK gene, resulting in a frameshift and premature termination of the protein. The patient presented at 2 months of age with poor feeding, hypotonia, nystagmus, metabolic acidosis, hepatomegaly, and elevated liver enzymes. She died at 5 months of age. Both parents and an unaffected sister were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12205643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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DGUOK, 2-BP DEL, 609GT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886037615 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037615;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=rs886037615" 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=rs886037615" 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=RCV000008634 OR RCV003555977" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000008634, RCV003555977" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000008634...</a>
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<p>In a patient with mitochondrial DNA depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>) with hepatic involvement, <a href="#6" class="mim-tip-reference" title="Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camano, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C. M., Feigenbaum, A., Naini, A. B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T. H. <strong>Mitochondrial DNA depletion and dGK gene mutations.</strong> Ann. Neurol. 52: 311-316, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205643</a>] [<a href="https://doi.org/10.1002/ana.10284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12205643">Salviati et al. (2002)</a> identified a homozygous 2-bp deletion (609delGT) in the DGUOK gene, resulting in a premature stop codon and a truncated protein. He presented with jaundice and hepatomegaly and died at 6 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12205643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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DGUOK, ARG142LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893631 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893631;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104893631?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893631" 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=rs104893631" 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=RCV000008635 OR RCV001545403" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000008635, RCV001545403" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000008635...</a>
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<p>In a patient with the hepatocerebral type of mitochondrial DNA depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>), <a href="#6" class="mim-tip-reference" title="Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camano, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C. M., Feigenbaum, A., Naini, A. B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T. H. <strong>Mitochondrial DNA depletion and dGK gene mutations.</strong> Ann. Neurol. 52: 311-316, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205643</a>] [<a href="https://doi.org/10.1002/ana.10284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12205643">Salviati et al. (2002)</a> identified compound heterozygosity for mutations in the DGUOK gene: a 425G-A transition resulting in an arg142-to-lys (R142K) substitution in a conserved area of the protein, likely affecting the enzyme's active site, and a 679G-A transition (<a href="#0006">601465.0006</a>) resulting in a glu227-to-lys (E227K) substitution in a conserved area of the protein, likely resulting in impaired folding of the protein. DGUOK activity was decreased, but not absent, in the patient's liver, indicating that the point mutations do not inactivate the enzyme to the same extent as truncating mutations. The patient underwent successful liver transplantation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12205643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893632 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893632;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104893632?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893632" 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=rs104893632" 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=RCV000008636 OR RCV001568974 OR RCV002512917 OR RCV004540991 OR RCV004795384" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000008636, RCV001568974, RCV002512917, RCV004540991, RCV004795384" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000008636...</a>
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<p>For discussion of the glu227-to-lys (E227K) mutation in the DGUOK gene that was found in compound heterozygous state in a patient with hepatocerebral-type mitochondrial DNA depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>) by <a href="#6" class="mim-tip-reference" title="Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camano, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C. M., Feigenbaum, A., Naini, A. B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T. H. <strong>Mitochondrial DNA depletion and dGK gene mutations.</strong> Ann. Neurol. 52: 311-316, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205643</a>] [<a href="https://doi.org/10.1002/ana.10284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12205643">Salviati et al. (2002)</a>, see <a href="#0005">601465.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12205643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104893633 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893633;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104893633?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104893633" 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=rs104893633" 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=RCV000008637 OR RCV004795385" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000008637, RCV004795385" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000008637...</a>
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<p>In 3 patients from 2 apparently unrelated Old Colony Mennonite families, each of whom had the hepatocerebral type of mitochondrial DNA depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>) associated with cystathioninuria, <a href="#10" class="mim-tip-reference" title="Tadiboyina, V. T., Rupar, A., Atkison, P. Feigenbaum, A., Kronick, J., Wang, J., Hegele, R. A. <strong>Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria.</strong> Am. J. Med. Genet. 135A: 289-291, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15887277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15887277</a>] [<a href="https://doi.org/10.1002/ajmg.a.30748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15887277">Tadiboyina et al. (2005)</a> identified homozygosity for a G-to-T transversion in the first nucleotide position of codon 255 in exon 6 of the DGUOK gene, resulting in an asp255-to-tyr (D255Y) substitution. All of the parents were unaffected and heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15887277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 MITOCHONDRIAL DNA DEPLETION SYNDROME 3</strong>
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PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4, INCLUDED<br />
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PORTAL HYPERTENSION, NONCIRRHOTIC, 1, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs763615602 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs763615602;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs763615602?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs763615602" 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=rs763615602" 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=RCV000239535 OR RCV000239586 OR RCV001550857 OR RCV001799645 OR RCV001824706" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239535, RCV000239586, RCV001550857, RCV001799645, RCV001824706" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239535...</a>
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<p><strong><em>Mitochondrial DNA Depletion Syndrome 3</em></strong></p><p>
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In a French boy with mitochondrial DNA depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>) with hepatic involvement only (<a href="#1" class="mim-tip-reference" title="Ducluzeau, P.-H., Lachaux, A., Bouvier, R., Duborjal, H., Stepien, G., Bozon, D., Mousson de Camaret, B. <strong>Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion.</strong> J. Hepatol. 36: 698-703, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11983456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11983456</a>] [<a href="https://doi.org/10.1016/s0168-8278(02)00021-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11983456">Ducluzeau et al., 2002</a>), <a href="#4" class="mim-tip-reference" title="Mousson de Camaret, B., Taanman, J. W., Padet, S., Chassagne, M., Mayencon, M., Clerc-Renaud, P., Mandon, G., Zabot, M.-T., Lachaux, A., Bozon, D. <strong>Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.</strong> Biochem. J. 402: 377-385, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17073823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17073823</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17073823[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/10.1042/BJ20060705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17073823">Mousson De Camaret et al. (2007)</a> identified compound heterozygous missense mutations in the DGUOK gene: a c.137A-G transition (c.137A-G, NM_080916) in exon 1, resulting in an asn46-to-ser (N46S) substitution at a conserved residue in the P-loop domain, and a c.797T-G transversion in exon 6, resulting in a leu266-to-arg (L266R; <a href="#0009">601465.0009</a>) substitution in the C-terminal alpha-9 helix domain. The patient had a very unusual disease course: he presented in infancy with severe liver disease, but then had spontaneous improvement beginning at about 32 months of age. He showed normal development by 4 years of age and ultimately had almost complete reversal of the phenotype; he never had neurologic involvement. In vitro studies by <a href="#4" class="mim-tip-reference" title="Mousson de Camaret, B., Taanman, J. W., Padet, S., Chassagne, M., Mayencon, M., Clerc-Renaud, P., Mandon, G., Zabot, M.-T., Lachaux, A., Bozon, D. <strong>Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.</strong> Biochem. J. 402: 377-385, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17073823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17073823</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17073823[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/10.1042/BJ20060705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17073823">Mousson De Camaret et al. (2007)</a> showed that these mutations retained 10 to 14% residual enzymatic activity, which likely contributed to the unusual phenotypic reversal in this patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11983456+17073823" 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="#7" class="mim-tip-reference" title="Sarzi, E., Bourdon, A., Chretien, D., Zarhrate, M., Corcos, J., Slama, A., Cormier-Daire, V., de Lonlay P., Munnich, A., Rotig, A. <strong>Mitochondrial DNA depletion is a prevalent cause of multiple respiratory chain deficiency in childhood.</strong> J. Pediat. 150: 531-534, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17452231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17452231</a>] [<a href="https://doi.org/10.1016/j.jpeds.2007.01.044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17452231">Sarzi et al. (2007)</a> identified a homozygous N46S mutation in a patient (patient 9) with MTDPS3 who developed progressive liver disease at 2 months of age and had liver failure with cirrhosis at age 10 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17452231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Autosomal Recessive Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions 4</em></strong></p><p>
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In a woman with features of MTDPS3, <a href="#5" class="mim-tip-reference" title="Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M. <strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong> Brain 135: 3404-3415, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23043144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23043144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23043144[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/brain/aws258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23043144">Ronchi et al. (2012)</a> identified compound heterozygous mutations in the DGUOK gene: N46S and a 2-bp deletion in exon 5 (c.605_606delGA; <a href="#0011">601465.0011</a>), resulting in a frameshift and premature termination (Arg202TyrfsTer12). She presented in infancy with liver failure and underwent successful liver transplant at age 9 months. She was clinically well until age 20 years, when she developed acute myopathic episodes associated with increased serum creatine kinase and rhabdomyolysis; this latter phenotype was consistent with autosomal recessive progressive external ophthalmoplegia-4 (PEOB4; <a href="/entry/617070">617070</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23043144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Noncirrhotic Portal Hypertension 1</em></strong></p><p>
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In 3 patients from 2 unrelated consanguineous Turkish families with noncirrhotic portal hypertension-1 (NCPH1; <a href="/entry/617068">617068</a>), <a href="#11" class="mim-tip-reference" title="Vilarinho, S., Sari, S., Yilmaz, G., Stiegler, A. L., Boggon, T. J., Jain, D., Akyol, G., Dalgic, B., Gunel, M., Lifton, R. P. <strong>Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.</strong> Hepatology 63: 1977-1986, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26874653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26874653</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26874653[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/10.1002/hep.28499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26874653">Vilarinho et al. (2016)</a> identified a homozygous N46S mutation. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families, and was not found in the 1000 Genomes Project database or in 894 control Turkish exomes. It was found at a very low frequency (3.134 x 10(-5)) in the ExAC database, only in the heterozygous state. Haplotype analysis suggested a founder effect. The findings significantly expanded the phenotype associated with the N46S mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26874653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 MITOCHONDRIAL DNA DEPLETION SYNDROME 3</strong>
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DGUOK, LEU266ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886037846 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037846;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=rs886037846" 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=rs886037846" 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=RCV001824707 OR RCV003556298" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001824707, RCV003556298" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001824707...</a>
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<p>For discussion of the c.797T-G transversion (c.797T-G, NM_080916) in exon 6 of the DGUOK gene, resulting in a leu266-to-arg (L266R) substitution, that was found in compound heterozygous state in a patient with mitochondrial DNA depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>) with only hepatic involvement by <a href="#4" class="mim-tip-reference" title="Mousson de Camaret, B., Taanman, J. W., Padet, S., Chassagne, M., Mayencon, M., Clerc-Renaud, P., Mandon, G., Zabot, M.-T., Lachaux, A., Bozon, D. <strong>Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.</strong> Biochem. J. 402: 377-385, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17073823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17073823</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17073823[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/10.1042/BJ20060705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17073823">Mousson De Camaret et al. (2007)</a>, see <a href="#0008">601465.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17073823" 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 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs144181978 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs144181978;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs144181978?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs144181978" 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=rs144181978" 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=RCV000195764 OR RCV000239593 OR RCV002517206 OR RCV003235120 OR RCV003895259 OR RCV005025316" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000195764, RCV000239593, RCV002517206, RCV003235120, RCV003895259, RCV005025316" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000195764...</a>
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<p>In 2 unrelated women (patients 1 and 2) with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; <a href="/entry/617070">617070</a>), <a href="#5" class="mim-tip-reference" title="Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M. <strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong> Brain 135: 3404-3415, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23043144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23043144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23043144[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/brain/aws258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23043144">Ronchi et al. (2012)</a> identified compound heterozygous mutations in the DGUOK gene. Both patients carried a c.462T-A transversion (c.462T-A, NM_080916.2) in exon 4, resulting in an asn154-to-lys (N154K) substitution at a highly conserved residue on 1 allele. One patient carried a 2-bp deletion in exon 5 (c.605_606delGA; <a href="#0011">601465.0011</a>), resulting in a frameshift and premature termination (Arg202TyrfsTer12), on the other allele, whereas the other patient carried a c.130G-A transition in exon 1, resulting in a glu44-to-lys (E44K; <a href="#0012">601465.0012</a>) substitution at a highly conserved residue, on the other allele. The N154K mutation was present at a low frequency in the Exome Variant Server database (0.04%) and the dbSNP database (0.002), but was not found in 226 control alleles. Both patients had decreased DGUOK protein levels and activity in skeletal muscle compared to controls. The E44K variant was not found in 226 control alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23043144" 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 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs863223949 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs863223949;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs863223949?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs863223949" 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=rs863223949" 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=RCV000196566 OR RCV000239503 OR RCV000239539" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000196566, RCV000239503, RCV000239539" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000196566...</a>
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<p>For discussion of the 2-bp deletion (c.605_606delGA, NM_080916.2) in exon 5 of the DGUOK gene, resulting in a frameshift and premature termination (Arg202TyrfsTer12), that was found in compound heterozygous state in a patient with features of both mitochondrial DNA depletion syndrome-3 (MTDPS3; <a href="/entry/251880">251880</a>) and autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; <a href="/entry/617070">617070</a>) by <a href="#5" class="mim-tip-reference" title="Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M. <strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong> Brain 135: 3404-3415, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23043144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23043144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23043144[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/brain/aws258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23043144">Ronchi et al. (2012)</a>, see <a href="#0008">601465.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23043144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs762550967 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs762550967;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs762550967?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs762550967" 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=rs762550967" 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=RCV000239555 OR RCV001782737" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239555, RCV001782737" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239555...</a>
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<p>For discussion of the c.130G-A transition (c.130G-A, NM_080916.2) in the DGUOK gene, resulting in a glu44-to-lys (E44K; <a href="#0012">601465.0012</a>) substitution, that was found in compound heterozygous state in a patient with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; <a href="/entry/617070">617070</a>), by <a href="#5" class="mim-tip-reference" title="Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M. <strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong> Brain 135: 3404-3415, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23043144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23043144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23043144[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/brain/aws258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23043144">Ronchi et al. (2012)</a>, see <a href="#0010">601465.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23043144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs74874677 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74874677;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs74874677?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs74874677" 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=rs74874677" 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=RCV000124677 OR RCV000239473 OR RCV000677030 OR RCV001139590 OR RCV002498597" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000124677, RCV000239473, RCV000677030, RCV001139590, RCV002498597" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000124677...</a>
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<p>In 3 patients, including 2 sibs, (patients 3, 5.1, and 5.2) with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; <a href="/entry/617070">617070</a>), <a href="#5" class="mim-tip-reference" title="Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M. <strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong> Brain 135: 3404-3415, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23043144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23043144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23043144[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/brain/aws258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23043144">Ronchi et al. (2012)</a> identified compound heterozygous mutations in the DGUOK gene. All 3 carried a heterozygous c.509A-G (c.509A-G, NM_080916.2) transition in exon 4, resulting in a gln170-to-arg (Q170R) substitution at a highly conserved residue. The Q107R variant was found at an allele frequency of 1.98% among a group of Italian controls, at a frequency of 1.6% in the Exome Variant Server database, and at a frequency of 0.029 in the dbSNP database. Functional studies of this variant were not performed, and the pathogenic significance was uncertain. Patient 3 carried a c.186C-A transversion in exon 2, resulting in a tyr62-to-ter (Y62X; <a href="#0014">601465.0014</a>) substitution in the other allele, whereas the sibs carried a C-to-G transversion in intron 3 (c.444-11C-G; <a href="#0015">601465.0015</a>) on the other allele, predicted to result in a splicing defect. Analysis of cells from patient 5.1 suggested that the splice site mutation resulted in nonsense-mediated mRNA decay. Analysis of skeletal muscle from 1 of the sibs showed decreased DGUOK protein and activity (70% reduction) to controls. Muscle samples were not available for study from patient 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23043144" 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>.0014 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</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">rs879255617 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs879255617;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=rs879255617" 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=rs879255617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the c.186C-A transversion (c.186C-A, NM_080916.2) in exon 2 of the DGUOK gene, resulting in a tyr62-to-ter (Y62X) substitution, that was found in compound heterozygous state in a patient with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; <a href="/entry/617070">617070</a>) by <a href="#5" class="mim-tip-reference" title="Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M. <strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong> Brain 135: 3404-3415, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23043144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23043144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23043144[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/brain/aws258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23043144">Ronchi et al. (2012)</a>, see <a href="#0013">601465.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23043144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0015 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</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">rs536746349 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs536746349;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=rs536746349" 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=rs536746349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the C-to-G transversion in intron 3 of the DGUOK gene (c.444-11C-G, NM_080916.2) resulting in a splicing defect and nonsense-mediated mRNA decay, that was found in compound heterozygous state in 2 sibs with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; <a href="/entry/617070">617070</a>) by <a href="#5" class="mim-tip-reference" title="Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M. <strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong> Brain 135: 3404-3415, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23043144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23043144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23043144[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/brain/aws258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23043144">Ronchi et al. (2012)</a>, see <a href="#0013">601465.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23043144" 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://doi.org/10.1016/s0168-8278(02)00021-1" target="_blank">Full Text</a>]
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<strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687800</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Mousson de Camaret, B., Taanman, J. W., Padet, S., Chassagne, M., Mayencon, M., Clerc-Renaud, P., Mandon, G., Zabot, M.-T., Lachaux, A., Bozon, D.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17073823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17073823</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17073823[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=17073823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M.
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<strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong>
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Brain 135: 3404-3415, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23043144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23043144</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23043144[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=23043144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/aws258" target="_blank">Full Text</a>]
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Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camano, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C. M., Feigenbaum, A., Naini, A. B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T. H.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12205643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Sarzi, E., Bourdon, A., Chretien, D., Zarhrate, M., Corcos, J., Slama, A., Cormier-Daire, V., de Lonlay P., Munnich, A., Rotig, A.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17452231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17452231</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17452231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Taanman2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Taanman, J.-W., Kateeb, I., Muntau, A. C., Jaksch, M., Cohen, N., Mandel, H.
|
|
<strong>A novel mutation in the deoxyguanosine kinase gene causing depletion of mitochondrial DNA.</strong>
|
|
Ann. Neurol. 52: 237-239, 2002.
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|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12210798/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12210798</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12210798" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.10247" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Taanman2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Taanman, J.-W., Muddle, J. R., Muntau, A. C.
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|
<strong>Mitochondrial DNA depletion can be prevented by dGMP and dAMP supplementation in a resting culture of deoxyguanosine kinase-deficient fibroblasts.</strong>
|
|
Hum. Molec. Genet. 12: 1839-1845, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12874104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12874104</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12874104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddg192" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Tadiboyina2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tadiboyina, V. T., Rupar, A., Atkison, P. Feigenbaum, A., Kronick, J., Wang, J., Hegele, R. A.
|
|
<strong>Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria.</strong>
|
|
Am. J. Med. Genet. 135A: 289-291, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15887277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15887277</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15887277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30748" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Vilarinho2016" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vilarinho, S., Sari, S., Yilmaz, G., Stiegler, A. L., Boggon, T. J., Jain, D., Akyol, G., Dalgic, B., Gunel, M., Lifton, R. P.
|
|
<strong>Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.</strong>
|
|
Hepatology 63: 1977-1986, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26874653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26874653</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26874653[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=26874653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/hep.28499" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Zhou2019" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhou, X., Curbo, S., Zhao, Q., Krishnan, S., Kuiper, R., Karlsson, A.
|
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<strong>Severe mtDNA depletion and dependency on catabolic lipid metabolism in DGUOK knockout mice.</strong>
|
|
Hum. Molec. Genet. 28: 2874-2884, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31127938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31127938</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31127938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddz103" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 11/04/2021
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 08/11/2016<br>Patricia A. Hartz - updated : 7/12/2005<br>George E. Tiller - updated : 5/4/2005<br>Cassandra L. Kniffin - updated : 12/13/2002<br>Cassandra L. Kniffin - updated : 10/2/2002<br>Victor A. McKusick - updated : 10/19/2001
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 10/10/1996
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 11/04/2021
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/03/2021<br>carol : 08/02/2021<br>ckniffin : 08/02/2021<br>carol : 08/18/2016<br>carol : 08/13/2016<br>carol : 08/12/2016<br>ckniffin : 08/11/2016<br>carol : 12/21/2010<br>ckniffin : 12/9/2010<br>carol : 9/13/2007<br>ckniffin : 8/31/2005<br>wwang : 7/18/2005<br>terry : 7/12/2005<br>tkritzer : 5/4/2005<br>carol : 12/17/2002<br>ckniffin : 12/13/2002<br>carol : 10/21/2002<br>ckniffin : 10/2/2002<br>alopez : 11/27/2001<br>alopez : 11/21/2001<br>carol : 10/24/2001<br>cwells : 10/23/2001<br>cwells : 10/23/2001<br>terry : 10/19/2001<br>carol : 5/30/2001<br>mark : 5/14/1997<br>mark : 10/11/1996<br>mark : 10/11/1996<br>mark : 10/10/1996
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 601465
|
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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DEOXYGUANOSINE KINASE; DGUOK
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
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DEOXYGUANOSINE KINASE, MITOCHONDRIAL; DGK
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: DGUOK</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 783734000;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 2p13.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 2:73,926,880-73,958,946 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
|
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
2p13.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
251880
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Portal hypertension, noncirrhotic, 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617068
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617070
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
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|
</div>
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<div>
|
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<br />
|
|
</div>
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<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Purine deoxyribonucleoside analogs are extensively used in treatment of lymphoproliferative disorders. These compounds are administered as pro-drugs, and their efficiency is dependent on intracellular phosphorylation to the corresponding triphosphates. In mammalian cells, the phosphorylation of purine deoxyribonucleosides is mediated predominantly by 2 deoxyribonucleoside kinases: cytosolic deoxycytidine kinase (DCK; EC 2.7.1.74; 125450) and mitochondrial deoxyguanosine kinase (DGK; EC 2.7.1.113).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Johansson and Karlsson (1996) used the human DCK cDNA sequence to find homologous cDNA sequences in an attempt to identify novel DCK-related enzymes. Several cDNA clones with 40 to 50% DNA sequence identity to human DCK were found in the GenBank sequence database, and the cDNA with the longest open reading frame was expressed in Escherichia coli. The protein was found to have the same substrate specificity as purified native DGK. Furthermore, the N-terminal sequence contained a possible mitochondrial translocation signal. Johansson and Karlsson (1996) suggested that DCK may be present only in the cytosol and DGK only in mitochondria. The presumed mitochondrial translocation signal would be removed by cleavage at a putative mitochondrial peptidase cleavage site to give a mature protein size of 28 kD. Northern blot analysis detected a 1.3-kb DGK transcript with no cross-hybridization to the 2.8-kb DCK mRNA. DGK mRNA was detected in all tissues investigated with the highest expression levels in muscle, brain, liver, and lymphoid tissues. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Mitochondrial DNA Depletion Syndrome 3 (Hepatocerebral Type)</em></strong></p><p>
|
|
Mandel et al. (2001) used homozygosity mapping in 3 kindreds of Druze origin to map a hepatocerebral type of mitochondrial DNA depletion syndrome (MTDPS3; 251880) to a region of 6.1 cM on chromosome 2p13. This interval encompasses the DGUOK gene. They identified a 1-bp deletion (601465.0001) within the DGUOK gene that segregated with the disease in the 3 kindreds studied. Affected individuals had early onset of progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion. Western blot analysis failed to detect DGK protein in the liver of affected persons. The main supply of deoxyribonucleotides (dNTPs) for mtDNA synthesis comes from the salvage pathway initiated by DGK and thymidine kinase-2 (TK2; 188250). The association of mtDNA depletion with mutated DGUOK suggested that the salvage pathway enzymes are involved in the maintenance of balanced mitochondrial dNTP pools. </p><p>Taanman et al. (2003) studied fibroblasts from a patient described by Taanman et al. (2002) who was homozygous for an arg105-to-ter substitution in the DGUOK gene (R105X; 601465.0002). Although mtDNA synthesis was cell cycle-independent in control fibroblasts, mtDNA synthesis occurred mainly during the S-phase in deoxyguanosine kinase-deficient cells. Consistent with this observation, the mtDNA content of exponentially growing, deoxyguanosine kinase-deficient cells was only mildly affected. When cycling was inhibited by serum deprivation and cells were in a resting state, however, the mtDNA content dropped considerably in deoxyguanosine kinase-deficient cells, yet remained stable in control fibroblasts. The decline in mtDNA content in resting, deoxyguanosine kinase-deficient cells could be prevented by deoxyguanosine monophosphate (DGMP) and deoxyadenosine monophosphate (dAMP) supplementation, providing conclusive evidence that substrate limitation triggers mtDNA depletion in deoxyguanosine kinase-deficient cells. </p><p>Tadiboyina et al. (2005) reported 3 patients with the hepatocerebral form of mtDNA depletion syndrome associated with cystathioninuria. All 3 children were homozygous for a mutation in the DGUOK gene (D255Y; 601465.0007), but had no mutations in the cystathionine gamma-lyase gene (CTH; 607657), indicating that the hepatocerebral form of mtDNA depletion syndrome might be associated with secondary cystathioninuria. </p><p><strong><em>Autosomal Recessive Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions 4</em></strong></p><p>
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In 6 patients, including 2 sibs, with adult-onset autosomal recessive progressive external ophthalmoplegia-4 (PEOB4; 617070), Ronchi et al. (2012) identified compound heterozygous mutations in the DGUOK gene (601465.0008; 601465.0010-601465.0015). One of the patients also had features of MTDPS3. The mutations, which were found by targeted exome sequencing and confirmed by standard sequencing, included both missense and truncating mutations. Skeletal muscle from patients showed mtDNA deletions as well as decreased protein levels and activity of DGUOK. The findings expanded the phenotype associated with DGUOK mutations. In this study, DGUOK mutations accounted for 5.6% of 90 probands with mtDNA deletions in skeletal muscle. </p><p><strong><em>Noncirrhotic Portal Hypertension 1</em></strong></p><p>
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In 3 patients from 2 unrelated consanguineous Turkish families with noncirrhotic portal hypertension-1 (NCPH1; 617068), Vilarinho et al. (2016) identified a homozygous missense mutation in the DGUOK gene (N46S; 601465.0008). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. </p>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Zhou et al. (2019) found that Dguok -/- mice appeared normal at birth but began to lose weight at week 6, with decreased adipose tissue and significantly higher relative weights of liver, kidney, and heart at week 8. Fur color changed from black to blueish gray beginning at week 16, with completion at week 20. Liver, brain, heart, and skeletal muscle of Dguok -/- mice showed mitochondrial DNA (mtDNA) deficiency, with liver most severely affected. Liver mitochondrial ultrastructure was abnormal, with decreased expression of mtDNA-encoded CoxI (MTCO1; 516030) and Nd1 (MTND1; 516000). Mitochondrial dysfunction led to liver damage, decreased subcutaneous fat, and accumulation of lipofuscin in liver tissue with increased oxidative stress. Microarray analysis of liver tissue revealed increased catabolic lipid metabolism and upregulation of the de novo dNTP pathway in Dguok -/- mice. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>15 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 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DGUOK, 1-BP DEL, 204A
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<br />
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SNP: rs886037613,
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ClinVar: RCV000008631, RCV000726828
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</span>
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</div>
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<span class="mim-text-font">
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<p>In affected members of 3 unrelated Israeli-Druze families with mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880), manifest with hepatic and cerebral involvement, Mandel et al. (2001) identified a homozygous 1-bp deletion (204delA) in the DGUOK gene, predicted to result in a frameshift and premature termination at codon 80. All parents carried the mutation, and unaffected sibs were either carriers or homozygous with respect to the wildtype allele. There were 19 affected members in the 3 kindreds. Death usually occurred before 1 year of age. Enzymatic activities of the mitochondrial respiratory chain complexes containing mtDNA-encoded subunits (complexes I, III, and IV) were reduced to various extents, whereas complex II enzymatic activity, which is encoded solely by nuclear genes, was normal. Muscle tissue from 7 affected patients showed normal histology and respiratory chain complex activities. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DGUOK, ARG105TER
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<br />
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SNP: rs104893630,
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gnomAD: rs104893630,
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ClinVar: RCV000008632, RCV002512916
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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 2 German brothers with mitochondrial DNA-depletion syndrome-3 (MTDPS3; 251880) characterized by lactic acidosis, hepatomegaly, hypoglycemia, jaundice, and encephalopathy with hypotonia, hyperreflexia, and nystagmus, Taanman et al. (2002) identified a homozygous 313C-T transition in exon 3 of the DGUOK gene, resulting in an arg105-to-ter (R105X) substitution, and a 173-amino acid truncation at the C terminus of the protein product. The unaffected parents were heterozygous for the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DGUOK, 4-BP DUP, 763GATT
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<br />
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SNP: rs763706988,
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gnomAD: rs763706988,
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ClinVar: RCV000008633, RCV000485369, RCV004528095, RCV005025033
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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 mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880), Salviati et al. (2002) identified a homozygous 4-bp duplication (GATT) at nucleotide 763 in the DGUOK gene, resulting in a frameshift and premature termination of the protein. The patient presented at 2 months of age with poor feeding, hypotonia, nystagmus, metabolic acidosis, hepatomegaly, and elevated liver enzymes. She died at 5 months of age. Both parents and an unaffected sister were heterozygous for the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DGUOK, 2-BP DEL, 609GT
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<br />
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SNP: rs886037615,
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ClinVar: RCV000008634, RCV003555977
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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 mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880) with hepatic involvement, Salviati et al. (2002) identified a homozygous 2-bp deletion (609delGT) in the DGUOK gene, resulting in a premature stop codon and a truncated protein. He presented with jaundice and hepatomegaly and died at 6 months of age. </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>.0005 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DGUOK, ARG142LYS
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<br />
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SNP: rs104893631,
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gnomAD: rs104893631,
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ClinVar: RCV000008635, RCV001545403
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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 the hepatocerebral type of mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880), Salviati et al. (2002) identified compound heterozygosity for mutations in the DGUOK gene: a 425G-A transition resulting in an arg142-to-lys (R142K) substitution in a conserved area of the protein, likely affecting the enzyme's active site, and a 679G-A transition (601465.0006) resulting in a glu227-to-lys (E227K) substitution in a conserved area of the protein, likely resulting in impaired folding of the protein. DGUOK activity was decreased, but not absent, in the patient's liver, indicating that the point mutations do not inactivate the enzyme to the same extent as truncating mutations. The patient underwent successful liver transplantation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0006 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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DGUOK, GLU227LYS
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<br />
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SNP: rs104893632,
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gnomAD: rs104893632,
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ClinVar: RCV000008636, RCV001568974, RCV002512917, RCV004540991, RCV004795384
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>For discussion of the glu227-to-lys (E227K) mutation in the DGUOK gene that was found in compound heterozygous state in a patient with hepatocerebral-type mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880) by Salviati et al. (2002), see 601465.0005. </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>.0007 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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DGUOK, ASP255TYR
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<br />
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|
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SNP: rs104893633,
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gnomAD: rs104893633,
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ClinVar: RCV000008637, RCV004795385
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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 3 patients from 2 apparently unrelated Old Colony Mennonite families, each of whom had the hepatocerebral type of mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880) associated with cystathioninuria, Tadiboyina et al. (2005) identified homozygosity for a G-to-T transversion in the first nucleotide position of codon 255 in exon 6 of the DGUOK gene, resulting in an asp255-to-tyr (D255Y) substitution. All of the parents were unaffected and heterozygous for the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0008 MITOCHONDRIAL DNA DEPLETION SYNDROME 3</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">
|
|
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4, INCLUDED<br />
|
|
PORTAL HYPERTENSION, NONCIRRHOTIC, 1, INCLUDED
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
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DGUOK, ASN46SER
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<br />
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SNP: rs763615602,
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gnomAD: rs763615602,
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ClinVar: RCV000239535, RCV000239586, RCV001550857, RCV001799645, RCV001824706
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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 />
|
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<p><strong><em>Mitochondrial DNA Depletion Syndrome 3</em></strong></p><p>
|
|
In a French boy with mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880) with hepatic involvement only (Ducluzeau et al., 2002), Mousson De Camaret et al. (2007) identified compound heterozygous missense mutations in the DGUOK gene: a c.137A-G transition (c.137A-G, NM_080916) in exon 1, resulting in an asn46-to-ser (N46S) substitution at a conserved residue in the P-loop domain, and a c.797T-G transversion in exon 6, resulting in a leu266-to-arg (L266R; 601465.0009) substitution in the C-terminal alpha-9 helix domain. The patient had a very unusual disease course: he presented in infancy with severe liver disease, but then had spontaneous improvement beginning at about 32 months of age. He showed normal development by 4 years of age and ultimately had almost complete reversal of the phenotype; he never had neurologic involvement. In vitro studies by Mousson De Camaret et al. (2007) showed that these mutations retained 10 to 14% residual enzymatic activity, which likely contributed to the unusual phenotypic reversal in this patient. </p><p>Sarzi et al. (2007) identified a homozygous N46S mutation in a patient (patient 9) with MTDPS3 who developed progressive liver disease at 2 months of age and had liver failure with cirrhosis at age 10 months. </p><p><strong><em>Autosomal Recessive Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions 4</em></strong></p><p>
|
|
In a woman with features of MTDPS3, Ronchi et al. (2012) identified compound heterozygous mutations in the DGUOK gene: N46S and a 2-bp deletion in exon 5 (c.605_606delGA; 601465.0011), resulting in a frameshift and premature termination (Arg202TyrfsTer12). She presented in infancy with liver failure and underwent successful liver transplant at age 9 months. She was clinically well until age 20 years, when she developed acute myopathic episodes associated with increased serum creatine kinase and rhabdomyolysis; this latter phenotype was consistent with autosomal recessive progressive external ophthalmoplegia-4 (PEOB4; 617070). </p><p><strong><em>Noncirrhotic Portal Hypertension 1</em></strong></p><p>
|
|
In 3 patients from 2 unrelated consanguineous Turkish families with noncirrhotic portal hypertension-1 (NCPH1; 617068), Vilarinho et al. (2016) identified a homozygous N46S mutation. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families, and was not found in the 1000 Genomes Project database or in 894 control Turkish exomes. It was found at a very low frequency (3.134 x 10(-5)) in the ExAC database, only in the heterozygous state. Haplotype analysis suggested a founder effect. The findings significantly expanded the phenotype associated with the N46S mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0009 MITOCHONDRIAL DNA DEPLETION SYNDROME 3</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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DGUOK, LEU266ARG
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<br />
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SNP: rs886037846,
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ClinVar: RCV001824707, RCV003556298
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.797T-G transversion (c.797T-G, NM_080916) in exon 6 of the DGUOK gene, resulting in a leu266-to-arg (L266R) substitution, that was found in compound heterozygous state in a patient with mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880) with only hepatic involvement by Mousson De Camaret et al. (2007), see 601465.0008. </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>.0010 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</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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DGUOK, ASN154LYS
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<br />
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SNP: rs144181978,
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gnomAD: rs144181978,
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ClinVar: RCV000195764, RCV000239593, RCV002517206, RCV003235120, RCV003895259, RCV005025316
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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 2 unrelated women (patients 1 and 2) with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; 617070), Ronchi et al. (2012) identified compound heterozygous mutations in the DGUOK gene. Both patients carried a c.462T-A transversion (c.462T-A, NM_080916.2) in exon 4, resulting in an asn154-to-lys (N154K) substitution at a highly conserved residue on 1 allele. One patient carried a 2-bp deletion in exon 5 (c.605_606delGA; 601465.0011), resulting in a frameshift and premature termination (Arg202TyrfsTer12), on the other allele, whereas the other patient carried a c.130G-A transition in exon 1, resulting in a glu44-to-lys (E44K; 601465.0012) substitution at a highly conserved residue, on the other allele. The N154K mutation was present at a low frequency in the Exome Variant Server database (0.04%) and the dbSNP database (0.002), but was not found in 226 control alleles. Both patients had decreased DGUOK protein levels and activity in skeletal muscle compared to controls. The E44K variant was not found in 226 control alleles. </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>.0011 MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4, 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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DGUOK, 2-BP DEL, 605GA
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<br />
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SNP: rs863223949,
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gnomAD: rs863223949,
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ClinVar: RCV000196566, RCV000239503, RCV000239539
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the 2-bp deletion (c.605_606delGA, NM_080916.2) in exon 5 of the DGUOK gene, resulting in a frameshift and premature termination (Arg202TyrfsTer12), that was found in compound heterozygous state in a patient with features of both mitochondrial DNA depletion syndrome-3 (MTDPS3; 251880) and autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; 617070) by Ronchi et al. (2012), see 601465.0008. </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>.0012 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</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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DGUOK, GLU44LYS
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<br />
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SNP: rs762550967,
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gnomAD: rs762550967,
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ClinVar: RCV000239555, RCV001782737
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of the c.130G-A transition (c.130G-A, NM_080916.2) in the DGUOK gene, resulting in a glu44-to-lys (E44K; 601465.0012) substitution, that was found in compound heterozygous state in a patient with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; 617070), by Ronchi et al. (2012), see 601465.0010. </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>.0013 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</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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DGUOK, GLN170ARG
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<br />
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SNP: rs74874677,
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gnomAD: rs74874677,
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ClinVar: RCV000124677, RCV000239473, RCV000677030, RCV001139590, RCV002498597
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|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 3 patients, including 2 sibs, (patients 3, 5.1, and 5.2) with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; 617070), Ronchi et al. (2012) identified compound heterozygous mutations in the DGUOK gene. All 3 carried a heterozygous c.509A-G (c.509A-G, NM_080916.2) transition in exon 4, resulting in a gln170-to-arg (Q170R) substitution at a highly conserved residue. The Q107R variant was found at an allele frequency of 1.98% among a group of Italian controls, at a frequency of 1.6% in the Exome Variant Server database, and at a frequency of 0.029 in the dbSNP database. Functional studies of this variant were not performed, and the pathogenic significance was uncertain. Patient 3 carried a c.186C-A transversion in exon 2, resulting in a tyr62-to-ter (Y62X; 601465.0014) substitution in the other allele, whereas the sibs carried a C-to-G transversion in intron 3 (c.444-11C-G; 601465.0015) on the other allele, predicted to result in a splicing defect. Analysis of cells from patient 5.1 suggested that the splice site mutation resulted in nonsense-mediated mRNA decay. Analysis of skeletal muscle from 1 of the sibs showed decreased DGUOK protein and activity (70% reduction) to controls. Muscle samples were not available for study from patient 3. </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>.0014 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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DGUOK, TYR62TER
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<br />
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SNP: rs879255617,
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ClinVar: RCV000239511
|
|
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</span>
|
|
</div>
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.186C-A transversion (c.186C-A, NM_080916.2) in exon 2 of the DGUOK gene, resulting in a tyr62-to-ter (Y62X) substitution, that was found in compound heterozygous state in a patient with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; 617070) by Ronchi et al. (2012), see 601465.0013. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
|
|
</div>
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|
|
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</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DGUOK, IVS3AS, C-G, -11
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs536746349,
|
|
|
|
|
|
|
|
ClinVar: RCV000239560, RCV000478803
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the C-to-G transversion in intron 3 of the DGUOK gene (c.444-11C-G, NM_080916.2) resulting in a splicing defect and nonsense-mediated mRNA decay, that was found in compound heterozygous state in 2 sibs with autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4; 617070) by Ronchi et al. (2012), see 601465.0013. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Ducluzeau, P.-H., Lachaux, A., Bouvier, R., Duborjal, H., Stepien, G., Bozon, D., Mousson de Camaret, B.
|
|
<strong>Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion.</strong>
|
|
J. Hepatol. 36: 698-703, 2002.
|
|
|
|
|
|
[PubMed: 11983456]
|
|
|
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|
|
[Full Text: https://doi.org/10.1016/s0168-8278(02)00021-1]
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|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Johansson, M., Karlsson, A.
|
|
<strong>Cloning and expression of human deoxyguanosine kinase cDNA.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 7258-7262, 1996.
|
|
|
|
|
|
[PubMed: 8692979]
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|
|
[Full Text: https://doi.org/10.1073/pnas.93.14.7258]
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</p>
|
|
</li>
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N.
|
|
<strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong>
|
|
Nature Genet. 29: 337-341, 2001. Note: Erratum: Nature Genet. 29: 491 only, 2001.
|
|
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|
|
[PubMed: 11687800]
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[Full Text: https://doi.org/10.1038/ng746]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Mousson de Camaret, B., Taanman, J. W., Padet, S., Chassagne, M., Mayencon, M., Clerc-Renaud, P., Mandon, G., Zabot, M.-T., Lachaux, A., Bozon, D.
|
|
<strong>Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.</strong>
|
|
Biochem. J. 402: 377-385, 2007.
|
|
|
|
|
|
[PubMed: 17073823]
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|
|
[Full Text: https://doi.org/10.1042/BJ20060705]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Ronchi, D., Garone, C., Bordoni, A., Gutierrez Rios, P., Calvo, S. E., Ripolone, M., Ranieri, M., Rizzuti, M., Villa, L., Magri, F., Corti, S., Bresolin, N., Mootha, V. K., Moggio, M., DiMauro, S., Comi, G. P., Sciacco, M.
|
|
<strong>Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions.</strong>
|
|
Brain 135: 3404-3415, 2012.
|
|
|
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|
|
[PubMed: 23043144]
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|
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[Full Text: https://doi.org/10.1093/brain/aws258]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camano, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C. M., Feigenbaum, A., Naini, A. B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T. H.
|
|
<strong>Mitochondrial DNA depletion and dGK gene mutations.</strong>
|
|
Ann. Neurol. 52: 311-316, 2002.
|
|
|
|
|
|
[PubMed: 12205643]
|
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|
|
[Full Text: https://doi.org/10.1002/ana.10284]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Sarzi, E., Bourdon, A., Chretien, D., Zarhrate, M., Corcos, J., Slama, A., Cormier-Daire, V., de Lonlay P., Munnich, A., Rotig, A.
|
|
<strong>Mitochondrial DNA depletion is a prevalent cause of multiple respiratory chain deficiency in childhood.</strong>
|
|
J. Pediat. 150: 531-534, 2007.
|
|
|
|
|
|
[PubMed: 17452231]
|
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|
|
[Full Text: https://doi.org/10.1016/j.jpeds.2007.01.044]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Taanman, J.-W., Kateeb, I., Muntau, A. C., Jaksch, M., Cohen, N., Mandel, H.
|
|
<strong>A novel mutation in the deoxyguanosine kinase gene causing depletion of mitochondrial DNA.</strong>
|
|
Ann. Neurol. 52: 237-239, 2002.
|
|
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|
|
[PubMed: 12210798]
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|
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[Full Text: https://doi.org/10.1002/ana.10247]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Taanman, J.-W., Muddle, J. R., Muntau, A. C.
|
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<strong>Mitochondrial DNA depletion can be prevented by dGMP and dAMP supplementation in a resting culture of deoxyguanosine kinase-deficient fibroblasts.</strong>
|
|
Hum. Molec. Genet. 12: 1839-1845, 2003.
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[PubMed: 12874104]
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[Full Text: https://doi.org/10.1093/hmg/ddg192]
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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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Tadiboyina, V. T., Rupar, A., Atkison, P. Feigenbaum, A., Kronick, J., Wang, J., Hegele, R. A.
|
|
<strong>Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria.</strong>
|
|
Am. J. Med. Genet. 135A: 289-291, 2005.
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|
|
[PubMed: 15887277]
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|
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[Full Text: https://doi.org/10.1002/ajmg.a.30748]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Vilarinho, S., Sari, S., Yilmaz, G., Stiegler, A. L., Boggon, T. J., Jain, D., Akyol, G., Dalgic, B., Gunel, M., Lifton, R. P.
|
|
<strong>Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.</strong>
|
|
Hepatology 63: 1977-1986, 2016.
|
|
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|
|
|
[PubMed: 26874653]
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|
|
[Full Text: https://doi.org/10.1002/hep.28499]
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</p>
|
|
</li>
|
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<li>
|
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<p class="mim-text-font">
|
|
Zhou, X., Curbo, S., Zhao, Q., Krishnan, S., Kuiper, R., Karlsson, A.
|
|
<strong>Severe mtDNA depletion and dependency on catabolic lipid metabolism in DGUOK knockout mice.</strong>
|
|
Hum. Molec. Genet. 28: 2874-2884, 2019.
|
|
|
|
|
|
[PubMed: 31127938]
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddz103]
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</p>
|
|
</li>
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</ol>
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<div>
|
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<br />
|
|
</div>
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</div>
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</div>
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<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Bao Lige - updated : 11/04/2021<br>Cassandra L. Kniffin - updated : 08/11/2016<br>Patricia A. Hartz - updated : 7/12/2005<br>George E. Tiller - updated : 5/4/2005<br>Cassandra L. Kniffin - updated : 12/13/2002<br>Cassandra L. Kniffin - updated : 10/2/2002<br>Victor A. McKusick - updated : 10/19/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
|
<div class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 10/10/1996
|
|
</span>
|
|
</div>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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