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Entry
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- *606521 - SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL THIAMINE PYROPHOSPHATE CARRIER), MEMBER 19; SLC25A19
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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">*606521</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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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>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606521">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=ENSG00000125454;t=ENST00000416858" 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=60386" 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=606521" 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 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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</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=ENSG00000125454;t=ENST00000416858" 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_001126121,NM_001126122,NM_021734,XM_005257559,XM_005257560,XM_005257561,XM_005257562,XM_006722007,XM_017024928,XM_047436512,XM_047436513,XM_047436514" 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_001126121" 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=606521" 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=08405&isoform_id=08405_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/SLC25A19" 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/10441012,12654491,12655374,13477293,13940227,20137652,22761199,33771670,45503786,57997187,119609673,119609674,119609675,186928856,186928858,186928860,193783634,530412630,530412632,530412634,530412636,578831220,1034600738,2217313143,2217313145,2217313148,2462556789,2462556791,2462556793,2462556795,2462556797,2462556799,2462556801,2462556803,2462556805" 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/Q9HC21" 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=60386" 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=ENSG00000125454;t=ENST00000416858" 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=SLC25A19" 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=SLC25A19" 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+60386" 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/SLC25A19" 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:60386" 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/60386" 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=chr17&hgg_gene=ENST00000416858.7&hgg_start=75272992&hgg_end=75289433&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:14409" 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:14409" 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/slc25a19" 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=606521[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=606521[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/ENSG00000125454" 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=SLC25A19" 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=SLC25A19" 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=SLC25A19" 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=SLC25A19&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/PA37879" 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:14409" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0035078.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1914533" 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/SLC25A19#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:1914533" 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/60386/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=60386" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00016588;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-050417-292" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
|
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</span>
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</span>
|
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</div>
|
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=SLC25A19&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> 702437000, 771305006<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>
|
|
606521
|
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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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SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL THIAMINE PYROPHOSPHATE CARRIER), MEMBER 19; SLC25A19
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</span>
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</h3>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MITOCHONDRIAL UNCOUPLING PROTEIN 1; MUP1<br />
|
|
MITOCHONDRIAL THIAMINE PYROPHOSPHATE CARRIER; TPC<br />
|
|
MITOCHONDRIAL DEOXYNUCLEOTIDE CARRIER, FORMERLY; DNC, FORMERLY
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SLC25A19" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SLC25A19</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/17/940?start=-3&limit=10&highlight=940">17q25.1</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:75272992-75289433&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'})">17:75,272,992-75,289,433</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=607196,613710" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/940?start=-3&limit=10&highlight=940">
|
|
17q25.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Microcephaly, Amish type
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/607196"> 607196 </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>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type)
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613710"> 613710 </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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<p>The SLC25A19 gene encodes a mitochondrial thiamine pyrophosphate carrier (<a href="#7" class="mim-tip-reference" title="Lindhurst, M. J., Fiermonte, G., Song, S., Struys, E., De Leonardis, F., Schwarzberg, P. L., Chen, A., Castegna, A., Verhoeven, N., Mathews, C. K., Palmieri, F., Biesecker, L. G. <strong>Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia.</strong> Proc. Nat. Acad. Sci. 103: 15927-15932, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17035501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17035501</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17035501[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0607661103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17035501">Lindhurst et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17035501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The inner membranes of mitochondria contain a family of proteins that transport various substances, including deoxynucleotides, into and out of the matrix. By phylogenetic analysis and EST database searching for mitochondrial carrier protein and adenine nucleotide carrier (ANC; see <a href="/entry/103220">103220</a>)-like sequences, <a href="#3" class="mim-tip-reference" title="Dolce, V., Fiermonte, G., Runswick, M. J., Palmieri, F., Walker, J. E. <strong>The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals.</strong> Proc. Nat. Acad. Sci. 98: 2284-2288, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11226231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11226231</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11226231[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.031430998" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11226231">Dolce et al. (2001)</a> obtained a cDNA encoding SLC25A19, which they termed DNC. The deduced 320-amino acid, 6-transmembrane DNC protein, which is 22% identical to mammalian ANCs, contains a P box, which is found in the DNA-binding domain of nuclear receptors. SDS-PAGE analysis showed that the purified recombinant protein has an apparent molecular mass of 36 kD. Functional analysis showed that DNC catalyzes the transport of all 4 deoxynucleotide diphosphates (dNDPs) and, less efficiently, the corresponding dNTPs in exchange for dNDPs, ADP, or ATP. It did not transport dNMPs, NMPs, deoxynucleosides, nucleosides, purines, or pyrimidines. RT-PCR analysis revealed expression of DNC in all tissues tested except placenta, with highest levels in colon, kidney, lung, testis, spleen, and brain. Immunoblot analysis detected expression in rat kidney, liver, and lung mitochondria. <a href="#3" class="mim-tip-reference" title="Dolce, V., Fiermonte, G., Runswick, M. J., Palmieri, F., Walker, J. E. <strong>The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals.</strong> Proc. Nat. Acad. Sci. 98: 2284-2288, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11226231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11226231</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11226231[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.031430998" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11226231">Dolce et al. (2001)</a> proposed that the greater efficiency of DNC in the exchange of dideoxy NTPs suggests that ddNDPs may be the best substrate transported by DNC and that DNC may be involved directly in the cytotoxicity of antiviral and anticancer nucleoside analogs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11226231" 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="Lindhurst, M. J., Fiermonte, G., Song, S., Struys, E., De Leonardis, F., Schwarzberg, P. L., Chen, A., Castegna, A., Verhoeven, N., Mathews, C. K., Palmieri, F., Biesecker, L. G. <strong>Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia.</strong> Proc. Nat. Acad. Sci. 103: 15927-15932, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17035501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17035501</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17035501[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0607661103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17035501">Lindhurst et al. (2006)</a> reported that Slc25a19 is a carrier of mitochondrial thiamine pyrophosphate (TPC). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17035501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By PCR and genomic sequence analysis, <a href="#5" class="mim-tip-reference" title="Iacobazzi, V., Ventura, M., Fiermonte, G., Prezioso, G., Rocchi, M., Palmieri, F. <strong>Genomic organization and mapping of the gene (SLC25A19) encoding the human mitochondrial deoxynucleotide carrier (DNC).</strong> Cytogenet. Cell Genet. 93: 40-42, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11474176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11474176</a>] [<a href="https://doi.org/10.1159/000056945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11474176">Iacobazzi et al. (2001)</a> determined that the SLC25A19 gene contains 9 exons and spans 16.5 kb. RT-PCR analysis suggested the existence of splice variants at the 5-prime end. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11474176" 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>Using FISH, <a href="#5" class="mim-tip-reference" title="Iacobazzi, V., Ventura, M., Fiermonte, G., Prezioso, G., Rocchi, M., Palmieri, F. <strong>Genomic organization and mapping of the gene (SLC25A19) encoding the human mitochondrial deoxynucleotide carrier (DNC).</strong> Cytogenet. Cell Genet. 93: 40-42, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11474176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11474176</a>] [<a href="https://doi.org/10.1159/000056945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11474176">Iacobazzi et al. (2001)</a> mapped the SLC25A19 gene to 17q25.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11474176" 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="#8" class="mim-tip-reference" title="Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G. <strong>Mutant deoxynucleotide carrier is associated with congenital microcephaly.</strong> Nature Genet. 32: 175-179, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12185364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12185364</a>] [<a href="https://doi.org/10.1038/ng948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12185364">Rosenberg et al. (2002)</a> found a homozygous mutation in the SLC25A19 gene (G177A: <a href="#0001">606521.0001</a>) to be the cause of Amish-type microcephaly (MCPHA; <a href="/entry/607196">607196</a>), also known as thiamine metabolism dysfunction syndrome-3 (THMD3). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12185364" 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>Thiamine Metabolism Dysfunction Syndrome 4</em></strong></p><p>
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By homozygosity mapping followed by candidate gene analysis of a consanguineous Arab Muslim family with bilateral striatal necrosis and progressive polyneuropathy due to thiamine metabolism dysfunction (THMD4; <a href="/entry/613710">613710</a>), <a href="#10" class="mim-tip-reference" title="Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O. <strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong> Ann. Neurol. 66: 419-424, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>] [<a href="https://doi.org/10.1002/ana.21752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19798730">Spiegel et al. (2009)</a> identified a homozygous mutation in the SLC25A19 gene (G125S; <a href="#0002">606521.0002</a>). <a href="#10" class="mim-tip-reference" title="Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O. <strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong> Ann. Neurol. 66: 419-424, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>] [<a href="https://doi.org/10.1002/ana.21752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19798730">Spiegel et al. (2009)</a> noted that the phenotype was less severe than that described in Amish lethal microcephaly, and suggested that the G125S mutation was less deleterious than the G177A mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19798730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an Italian patient, born to consanguineous parents, with THMD4, <a href="#1" class="mim-tip-reference" title="Bottega, R., Perrone, M. D., Vecchiato, K., Taddio, A., Sabui, S., Pecile, V., Said, H. M., Faletra, F. <strong>Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4.</strong> J. Hum. Genet. 64: 1075-1081, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31506564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31506564</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31506564[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/10.1038/s10038-019-0666-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31506564">Bottega et al. (2019)</a> identified a homozygous mutation in the SLC25A19 gene (Q192H; <a href="#0003">606521.0003</a>). SLC25A19 with the Q192H mutation in HepG2 cells showed reduced expression in mitochondrial and whole cell homogenates compared to wildtype. The patient had clinical features of episodic encephalopathy and progressive axonal polyneuropathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31506564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated Indian children, born to consanguineous parents, with THMD4, <a href="#4" class="mim-tip-reference" title="Gowda, V. K., Srinivasan, V. M., Jehta, K., Bhat, M. D. <strong>Bilateral striatal necrosis with polyneuropathy with a novel SLC25A19 (mitochondrial thiamine pyrophosphate carrier OMIM*606521) mutation: treatable thiamine metabolic disorder--a report of two Indian cases.</strong> Neuropediatrics 50: 313-317, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31295743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31295743</a>] [<a href="https://doi.org/10.1055/s-0039-1693148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31295743">Gowda et al. (2019)</a> identified homozygous missense mutations in the SLC25A19 gene (E304K, <a href="#0004">606521.0004</a>; L290Q, <a href="#0005">606521.0005</a>). The mutations, which were found by next-generation sequencing and confirmed by Sanger sequencing, were identified in heterozygous state in both sets of parents. Functional studies were not performed. Both patients presented with recurrent episodes of flaccid paralysis and encephalopathy following febrile illness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31295743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Li, D., Song, J., Li, X., Liu, Y., Dong, H., Kang, L., Liu, Y., Zhang, Y., Jin, Y., Guan, H., Zhou, C., Yang, Y. <strong>Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome.</strong> Europ. J. Med. Genet. 63: 104003, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32679198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32679198</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.104003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32679198">Li et al. (2020)</a> identified compound heterozygous mutations in the SLC25A19 gene in 2 patients with THMD4: A65V and P152T (patient 5) and A161T and A184P (patient 6). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were identified in the carrier state in the parents. Functional studies were not performed. Both patients had recurrent encephalopathic episodes, abnormal signal in the putamen and caudate nucleus on brain MRI, and elevated alpha-ketoglutarate in the urine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32679198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Chen, Y., Fang, B., Hu, X., Guo, R., Guo, J., Fang, K., Ni, J., Li, W., Qian, S., Hao, C. <strong>Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.</strong> Orphanet J. Rare Dis. 16: 403, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34587972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34587972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34587972[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/10.1186/s13023-021-02028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34587972">Chen et al. (2021)</a> identified compound heterozygous mutations in the SLC25A19 gene in 2 Chinese sibs (G26R, <a href="#0006">606521.0006</a> and F249I, <a href="#0007">606521.0007</a>) and an unrelated Chinese child (A57T and A128V) with THMD4. Transfection of each mutation into HEK293 cells resulted in decreased mitochondrial thiamine pyrophosphate (TPP) compared to wildtype, indicative of deficient TPP transport. All 3 patients presented with basal ganglia changes on brain MRI following fever. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34587972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 Turkish sibs and an unrelated Turkish patient with THMD4, <a href="#9" class="mim-tip-reference" title="Samur, B. M., Gumus, G., Canpolat, M., Gumus, H., Per, H., Caglayan, A. O. <strong>Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature.</strong> Clin. Dysmorph. 31: 125-131, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35102031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35102031</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35102031">Samur et al. (2022)</a> identified homozygosity for a previously reported missense mutation in the SLC25A19 gene (Q192H; <a href="#0003">606521.0003</a>). The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35102031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Lindhurst, M. J., Fiermonte, G., Song, S., Struys, E., De Leonardis, F., Schwarzberg, P. L., Chen, A., Castegna, A., Verhoeven, N., Mathews, C. K., Palmieri, F., Biesecker, L. G. <strong>Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia.</strong> Proc. Nat. Acad. Sci. 103: 15927-15932, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17035501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17035501</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17035501[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0607661103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17035501">Lindhurst et al. (2006)</a> found that Slc25a19-knockout mice had 100% prenatal lethality by embryonic day 12. Affected embryos had neural tube closure defects with ruffling of the neural fold ridges, yolk sac erythropoietic failure, and increased alpha-ketoglutarate in the amniotic fluid. Mitochondria from these animals showed normal levels of RNA and DNA, suggesting that transport of these molecules is not a primary role of Slc25a19. In contrast, mitochondria from these animals and from cells of patients with MCPHA had undetectable and decreased thiamine pyrophosphate levels, respectively, resulting in dysfunction of the alpha-ketoglutarate dehydrogenase complex (see <a href="/entry/126063">126063</a>). The findings indicated that transport of this molecule is a candidate function of Slc25a19. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17035501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs119473030 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119473030;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=rs119473030" 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=rs119473030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#8" class="mim-tip-reference" title="Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G. <strong>Mutant deoxynucleotide carrier is associated with congenital microcephaly.</strong> Nature Genet. 32: 175-179, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12185364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12185364</a>] [<a href="https://doi.org/10.1038/ng948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12185364">Rosenberg et al. (2002)</a> demonstrated that Amish-type microcephaly (MCPHA; <a href="/entry/607196">607196</a>), also known as thiamine metabolism dysfunction syndrome-3 (THMD3), is caused by homozygosity for a c.530G-C transversion in the SLC25A19 gene, predicted to result in a gly177-to-ala (G177A) substitution in the first residue of the fourth transmembrane domain (<a href="#10" class="mim-tip-reference" title="Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O. <strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong> Ann. Neurol. 66: 419-424, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>] [<a href="https://doi.org/10.1002/ana.21752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19798730">Spiegel et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12185364+19798730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906944 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906944;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=rs387906944" 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=rs387906944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 4 affected sibs, born of consanguineous Arab Muslim parents, with bilateral striatal necrosis and progressive polyneuropathy due to thiamine metabolism dysfunction-4 (THMD4; <a href="/entry/613710">613710</a>), <a href="#10" class="mim-tip-reference" title="Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O. <strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong> Ann. Neurol. 66: 419-424, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>] [<a href="https://doi.org/10.1002/ana.21752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19798730">Spiegel et al. (2009)</a> identified a homozygous c.373G-A transition in the SLC25A19 gene, resulting in a gly125-to-ser (G125S) substitution in the highly conserved first residue of the third transmembrane domain. Functional complementation studies in yeast showed decreased protein function compared to controls. The phenotype was characterized by recurrent encephalopathic episodes in childhood with essentially full psychomotor recovery, as well as by a chronic progressive polyneuropathy. Cognition was intact. <a href="#10" class="mim-tip-reference" title="Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O. <strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong> Ann. Neurol. 66: 419-424, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>] [<a href="https://doi.org/10.1002/ana.21752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19798730">Spiegel et al. (2009)</a> noted that the phenotype was much less severe than that described in Amish lethal microcephaly (<a href="/entry/607196">607196</a>), and suggested that the G125S mutation was less deleterious than the G177A mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19798730" 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 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY 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">rs1300370754 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1300370754;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=rs1300370754" 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=rs1300370754" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Italian patient, born to consanguineous parents, with thiamine metabolism dysfunction syndrome-4 (THMD4; <a href="/entry/613710">613710</a>), <a href="#1" class="mim-tip-reference" title="Bottega, R., Perrone, M. D., Vecchiato, K., Taddio, A., Sabui, S., Pecile, V., Said, H. M., Faletra, F. <strong>Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4.</strong> J. Hum. Genet. 64: 1075-1081, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31506564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31506564</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31506564[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/10.1038/s10038-019-0666-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31506564">Bottega et al. (2019)</a> identified a homozygous c.576G-C transversion at a conserved site in exon 6 of the SLC25A19 gene, resulting in a gln192-to-his (Q192H) substitution. The mutation, which was identified by a combination of homozygosity mapping and sequencing of the SLC25A19 gene, was present in heterozygous state in the parents. The mutation was not present in the ExAC, 1000 Genomes Project, and gnomAD databases. Expression of SLC25A19 with the Q192H mutation into HepG2 cells showed reduced protein expression in mitochondrial and whole cell homogenates compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31506564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 Turkish brothers and an unrelated Turkish female with THMD4, <a href="#9" class="mim-tip-reference" title="Samur, B. M., Gumus, G., Canpolat, M., Gumus, H., Per, H., Caglayan, A. O. <strong>Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature.</strong> Clin. Dysmorph. 31: 125-131, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35102031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35102031</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35102031">Samur et al. (2022)</a> identified homozygosity for the Q192H mutation in the SLC25A19 gene. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with disease in the families. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35102031" 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 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY 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">rs2145724052 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2145724052;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=rs2145724052" 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=rs2145724052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Indian boy, born to consanguineous parents, with thiamine metabolism dysfunction syndrome-4 (THMD4; <a href="/entry/613710">613710</a>), <a href="#4" class="mim-tip-reference" title="Gowda, V. K., Srinivasan, V. M., Jehta, K., Bhat, M. D. <strong>Bilateral striatal necrosis with polyneuropathy with a novel SLC25A19 (mitochondrial thiamine pyrophosphate carrier OMIM*606521) mutation: treatable thiamine metabolic disorder--a report of two Indian cases.</strong> Neuropediatrics 50: 313-317, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31295743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31295743</a>] [<a href="https://doi.org/10.1055/s-0039-1693148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31295743">Gowda et al. (2019)</a> identified a homozygous c.910G-A transition in the SLC25A19 gene, resulting in a glu304-to-lys (E304K) substitution. The mutation, which was found by next-generation sequencing and confirmed by Sanger sequencing, was identified in heterozygous state in the parents. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31295743" 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 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY 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> rs750590533 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs750590533;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/rs750590533?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=rs750590533" 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=rs750590533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Indian girl, born to consanguineous parents, with thiamine metabolism dysfunction syndrome-4 (THMD4; <a href="/entry/613710">613710</a>), <a href="#4" class="mim-tip-reference" title="Gowda, V. K., Srinivasan, V. M., Jehta, K., Bhat, M. D. <strong>Bilateral striatal necrosis with polyneuropathy with a novel SLC25A19 (mitochondrial thiamine pyrophosphate carrier OMIM*606521) mutation: treatable thiamine metabolic disorder--a report of two Indian cases.</strong> Neuropediatrics 50: 313-317, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31295743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31295743</a>] [<a href="https://doi.org/10.1055/s-0039-1693148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31295743">Gowda et al. (2019)</a> identified a homozygous c.869T-A transversion in the SLC25A19 gene, resulting in a leu290-to-gln (L290Q) substitution. The mutation, which was identified with next generation sequencing and confirmed with Sanger sequencing, was found in the heterozygous state in both parents. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31295743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE)</strong>
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<p>In 2 Chinese sibs (patients 2 and 3) with thiamine metabolism dysfunction syndrome-4 (THMD4; <a href="/entry/613710">613710</a>), <a href="#2" class="mim-tip-reference" title="Chen, Y., Fang, B., Hu, X., Guo, R., Guo, J., Fang, K., Ni, J., Li, W., Qian, S., Hao, C. <strong>Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.</strong> Orphanet J. Rare Dis. 16: 403, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34587972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34587972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34587972[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/10.1186/s13023-021-02028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34587972">Chen et al. (2021)</a> identified compound heterozygous mutations in the SLC25A19 gene: a c.76G-A transition (c.76G-A, NM_001126122), resulting in a gly26-to-arg (G26R) substitution, and a c.745T-A transversion, resulting in a phe249-to-ile (F249I; <a href="#0007">606521.0007</a>) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were present in heterozygous state in the parents. The G26R mutation was present in the gnomAD database at a frequency of 0.0005 in the East Asian population. The F249I mutation was not present in the gnomAD database in the East Asian population. Transfection of each mutation into HEK293 cells resulted in deficient mitochondrial transport of thiamine pyrophosphate compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34587972" 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>For discussion of the c.745T-A transversion (c.745T-A, NM_001126122) in the SLC25A19 gene, resulting in a phe249-to-ile (F249I) substitution, that was identified in compound heterozygous state in 2 Chinese sibs with thiamine metabolism dysfunction syndrome-4 (THMD4; <a href="/entry/613710">613710</a>) by <a href="#2" class="mim-tip-reference" title="Chen, Y., Fang, B., Hu, X., Guo, R., Guo, J., Fang, K., Ni, J., Li, W., Qian, S., Hao, C. <strong>Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.</strong> Orphanet J. Rare Dis. 16: 403, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34587972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34587972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34587972[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/10.1186/s13023-021-02028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34587972">Chen et al. (2021)</a>, see <a href="#0006">606521.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34587972" 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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Bottega, R., Perrone, M. D., Vecchiato, K., Taddio, A., Sabui, S., Pecile, V., Said, H. M., Faletra, F.
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<strong>Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4.</strong>
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J. Hum. Genet. 64: 1075-1081, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31506564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31506564</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31506564[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=31506564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s10038-019-0666-5" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
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<a id="Chen2021" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Chen, Y., Fang, B., Hu, X., Guo, R., Guo, J., Fang, K., Ni, J., Li, W., Qian, S., Hao, C.
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<strong>Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.</strong>
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Orphanet J. Rare Dis. 16: 403, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34587972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34587972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34587972[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=34587972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1186/s13023-021-02028-4" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
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<a id="Dolce2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Dolce, V., Fiermonte, G., Runswick, M. J., Palmieri, F., Walker, J. E.
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<strong>The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals.</strong>
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Proc. Nat. Acad. Sci. 98: 2284-2288, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11226231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11226231</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11226231[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=11226231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.031430998" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
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<a id="Gowda2019" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gowda, V. K., Srinivasan, V. M., Jehta, K., Bhat, M. D.
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<strong>Bilateral striatal necrosis with polyneuropathy with a novel SLC25A19 (mitochondrial thiamine pyrophosphate carrier OMIM*606521) mutation: treatable thiamine metabolic disorder--a report of two Indian cases.</strong>
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Neuropediatrics 50: 313-317, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31295743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31295743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31295743" 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/10.1055/s-0039-1693148" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
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<a id="Iacobazzi2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Iacobazzi, V., Ventura, M., Fiermonte, G., Prezioso, G., Rocchi, M., Palmieri, F.
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<strong>Genomic organization and mapping of the gene (SLC25A19) encoding the human mitochondrial deoxynucleotide carrier (DNC).</strong>
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Cytogenet. Cell Genet. 93: 40-42, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11474176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11474176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11474176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000056945" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
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<a id="Li2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Li, D., Song, J., Li, X., Liu, Y., Dong, H., Kang, L., Liu, Y., Zhang, Y., Jin, Y., Guan, H., Zhou, C., Yang, Y.
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<strong>Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome.</strong>
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Europ. J. Med. Genet. 63: 104003, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32679198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32679198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32679198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ejmg.2020.104003" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Lindhurst2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lindhurst, M. J., Fiermonte, G., Song, S., Struys, E., De Leonardis, F., Schwarzberg, P. L., Chen, A., Castegna, A., Verhoeven, N., Mathews, C. K., Palmieri, F., Biesecker, L. G.
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<strong>Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia.</strong>
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Proc. Nat. Acad. Sci. 103: 15927-15932, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17035501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17035501</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17035501[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=17035501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0607661103" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Rosenberg2002" class="mim-anchor"></a>
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<div class="">
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Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G.
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<strong>Mutant deoxynucleotide carrier is associated with congenital microcephaly.</strong>
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Nature Genet. 32: 175-179, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12185364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12185364</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12185364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng948" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Samur2022" class="mim-anchor"></a>
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<div class="">
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Samur, B. M., Gumus, G., Canpolat, M., Gumus, H., Per, H., Caglayan, A. O.
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<strong>Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature.</strong>
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Clin. Dysmorph. 31: 125-131, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35102031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35102031</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35102031" 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/10.1097/MCD.0000000000000411" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Spiegel2009" class="mim-anchor"></a>
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<div class="">
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Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O.
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<strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong>
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Ann. Neurol. 66: 419-424, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19798730" 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.21752" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 08/26/2022
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 07/08/2022<br>Cassandra L. Kniffin - updated : 2/8/2012<br>Cassandra L. Kniffin - updated : 1/24/2011<br>Cassandra L. Kniffin - updated : 11/9/2006<br>Victor A. McKusick - updated : 8/29/2002
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<a id="creationDate" class="mim-anchor"></a>
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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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<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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Paul J. Converse : 11/30/2001
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carol : 08/26/2022
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<span class="mim-text-font">
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carol : 07/11/2022<br>carol : 07/08/2022<br>carol : 02/10/2012<br>ckniffin : 2/8/2012<br>wwang : 2/16/2011<br>ckniffin : 1/24/2011<br>carol : 9/22/2009<br>wwang : 11/20/2006<br>ckniffin : 11/9/2006<br>tkritzer : 9/6/2002<br>tkritzer : 9/3/2002<br>terry : 8/29/2002<br>mgross : 11/30/2001
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<span class="mim-font">
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<strong>*</strong> 606521
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<div>
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<h3>
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<span class="mim-font">
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SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL THIAMINE PYROPHOSPHATE CARRIER), MEMBER 19; SLC25A19
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</span>
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</h3>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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MITOCHONDRIAL UNCOUPLING PROTEIN 1; MUP1<br />
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MITOCHONDRIAL THIAMINE PYROPHOSPHATE CARRIER; TPC<br />
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MITOCHONDRIAL DEOXYNUCLEOTIDE CARRIER, FORMERLY; DNC, FORMERLY
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SLC25A19</em></strong>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 702437000, 771305006;
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<strong>
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<em>
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Cytogenetic location: 17q25.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:75,272,992-75,289,433 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
17q25.1
|
|
</span>
|
|
</td>
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Microcephaly, Amish type
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
607196
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
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|
|
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|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type)
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613710
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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|
|
<div>
|
|
<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>The SLC25A19 gene encodes a mitochondrial thiamine pyrophosphate carrier (Lindhurst et al., 2006). </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>The inner membranes of mitochondria contain a family of proteins that transport various substances, including deoxynucleotides, into and out of the matrix. By phylogenetic analysis and EST database searching for mitochondrial carrier protein and adenine nucleotide carrier (ANC; see 103220)-like sequences, Dolce et al. (2001) obtained a cDNA encoding SLC25A19, which they termed DNC. The deduced 320-amino acid, 6-transmembrane DNC protein, which is 22% identical to mammalian ANCs, contains a P box, which is found in the DNA-binding domain of nuclear receptors. SDS-PAGE analysis showed that the purified recombinant protein has an apparent molecular mass of 36 kD. Functional analysis showed that DNC catalyzes the transport of all 4 deoxynucleotide diphosphates (dNDPs) and, less efficiently, the corresponding dNTPs in exchange for dNDPs, ADP, or ATP. It did not transport dNMPs, NMPs, deoxynucleosides, nucleosides, purines, or pyrimidines. RT-PCR analysis revealed expression of DNC in all tissues tested except placenta, with highest levels in colon, kidney, lung, testis, spleen, and brain. Immunoblot analysis detected expression in rat kidney, liver, and lung mitochondria. Dolce et al. (2001) proposed that the greater efficiency of DNC in the exchange of dideoxy NTPs suggests that ddNDPs may be the best substrate transported by DNC and that DNC may be involved directly in the cytotoxicity of antiviral and anticancer nucleoside analogs. </p><p>Lindhurst et al. (2006) reported that Slc25a19 is a carrier of mitochondrial thiamine pyrophosphate (TPC). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By PCR and genomic sequence analysis, Iacobazzi et al. (2001) determined that the SLC25A19 gene contains 9 exons and spans 16.5 kb. RT-PCR analysis suggested the existence of splice variants at the 5-prime end. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using FISH, Iacobazzi et al. (2001) mapped the SLC25A19 gene to 17q25.3. </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>Microcephaly, Amish Type</em></strong></p><p>
|
|
Rosenberg et al. (2002) found a homozygous mutation in the SLC25A19 gene (G177A: 606521.0001) to be the cause of Amish-type microcephaly (MCPHA; 607196), also known as thiamine metabolism dysfunction syndrome-3 (THMD3). </p><p><strong><em>Thiamine Metabolism Dysfunction Syndrome 4</em></strong></p><p>
|
|
By homozygosity mapping followed by candidate gene analysis of a consanguineous Arab Muslim family with bilateral striatal necrosis and progressive polyneuropathy due to thiamine metabolism dysfunction (THMD4; 613710), Spiegel et al. (2009) identified a homozygous mutation in the SLC25A19 gene (G125S; 606521.0002). Spiegel et al. (2009) noted that the phenotype was less severe than that described in Amish lethal microcephaly, and suggested that the G125S mutation was less deleterious than the G177A mutation. </p><p>In an Italian patient, born to consanguineous parents, with THMD4, Bottega et al. (2019) identified a homozygous mutation in the SLC25A19 gene (Q192H; 606521.0003). SLC25A19 with the Q192H mutation in HepG2 cells showed reduced expression in mitochondrial and whole cell homogenates compared to wildtype. The patient had clinical features of episodic encephalopathy and progressive axonal polyneuropathy. </p><p>In 2 unrelated Indian children, born to consanguineous parents, with THMD4, Gowda et al. (2019) identified homozygous missense mutations in the SLC25A19 gene (E304K, 606521.0004; L290Q, 606521.0005). The mutations, which were found by next-generation sequencing and confirmed by Sanger sequencing, were identified in heterozygous state in both sets of parents. Functional studies were not performed. Both patients presented with recurrent episodes of flaccid paralysis and encephalopathy following febrile illness. </p><p>Li et al. (2020) identified compound heterozygous mutations in the SLC25A19 gene in 2 patients with THMD4: A65V and P152T (patient 5) and A161T and A184P (patient 6). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were identified in the carrier state in the parents. Functional studies were not performed. Both patients had recurrent encephalopathic episodes, abnormal signal in the putamen and caudate nucleus on brain MRI, and elevated alpha-ketoglutarate in the urine. </p><p>Chen et al. (2021) identified compound heterozygous mutations in the SLC25A19 gene in 2 Chinese sibs (G26R, 606521.0006 and F249I, 606521.0007) and an unrelated Chinese child (A57T and A128V) with THMD4. Transfection of each mutation into HEK293 cells resulted in decreased mitochondrial thiamine pyrophosphate (TPP) compared to wildtype, indicative of deficient TPP transport. All 3 patients presented with basal ganglia changes on brain MRI following fever. </p><p>In 2 Turkish sibs and an unrelated Turkish patient with THMD4, Samur et al. (2022) identified homozygosity for a previously reported missense mutation in the SLC25A19 gene (Q192H; 606521.0003). The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Lindhurst et al. (2006) found that Slc25a19-knockout mice had 100% prenatal lethality by embryonic day 12. Affected embryos had neural tube closure defects with ruffling of the neural fold ridges, yolk sac erythropoietic failure, and increased alpha-ketoglutarate in the amniotic fluid. Mitochondria from these animals showed normal levels of RNA and DNA, suggesting that transport of these molecules is not a primary role of Slc25a19. In contrast, mitochondria from these animals and from cells of patients with MCPHA had undetectable and decreased thiamine pyrophosphate levels, respectively, resulting in dysfunction of the alpha-ketoglutarate dehydrogenase complex (see 126063). The findings indicated that transport of this molecule is a candidate function of Slc25a19. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>7 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MICROCEPHALY, AMISH TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC25A19, GLY177ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119473030,
|
|
|
|
|
|
|
|
ClinVar: RCV000004490
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Rosenberg et al. (2002) demonstrated that Amish-type microcephaly (MCPHA; 607196), also known as thiamine metabolism dysfunction syndrome-3 (THMD3), is caused by homozygosity for a c.530G-C transversion in the SLC25A19 gene, predicted to result in a gly177-to-ala (G177A) substitution in the first residue of the fourth transmembrane domain (Spiegel et al., 2009). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC25A19, GLY125SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906944,
|
|
|
|
|
|
|
|
ClinVar: RCV000023554, RCV001847622
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected sibs, born of consanguineous Arab Muslim parents, with bilateral striatal necrosis and progressive polyneuropathy due to thiamine metabolism dysfunction-4 (THMD4; 613710), Spiegel et al. (2009) identified a homozygous c.373G-A transition in the SLC25A19 gene, resulting in a gly125-to-ser (G125S) substitution in the highly conserved first residue of the third transmembrane domain. Functional complementation studies in yeast showed decreased protein function compared to controls. The phenotype was characterized by recurrent encephalopathic episodes in childhood with essentially full psychomotor recovery, as well as by a chronic progressive polyneuropathy. Cognition was intact. Spiegel et al. (2009) noted that the phenotype was much less severe than that described in Amish lethal microcephaly (607196), and suggested that the G125S mutation was less deleterious than the G177A mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC25A19, GLN192HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1300370754,
|
|
|
|
|
|
|
|
ClinVar: RCV002264842
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient, born to consanguineous parents, with thiamine metabolism dysfunction syndrome-4 (THMD4; 613710), Bottega et al. (2019) identified a homozygous c.576G-C transversion at a conserved site in exon 6 of the SLC25A19 gene, resulting in a gln192-to-his (Q192H) substitution. The mutation, which was identified by a combination of homozygosity mapping and sequencing of the SLC25A19 gene, was present in heterozygous state in the parents. The mutation was not present in the ExAC, 1000 Genomes Project, and gnomAD databases. Expression of SLC25A19 with the Q192H mutation into HepG2 cells showed reduced protein expression in mitochondrial and whole cell homogenates compared to wildtype. </p><p>In 2 Turkish brothers and an unrelated Turkish female with THMD4, Samur et al. (2022) identified homozygosity for the Q192H mutation in the SLC25A19 gene. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with disease in the families. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC25A19, GLU304LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2145724052,
|
|
|
|
|
|
|
|
ClinVar: RCV002264846
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Indian boy, born to consanguineous parents, with thiamine metabolism dysfunction syndrome-4 (THMD4; 613710), Gowda et al. (2019) identified a homozygous c.910G-A transition in the SLC25A19 gene, resulting in a glu304-to-lys (E304K) substitution. The mutation, which was found by next-generation sequencing and confirmed by Sanger sequencing, was identified in heterozygous state in the parents. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC25A19, LEU290GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs750590533,
|
|
|
|
|
|
gnomAD: rs750590533,
|
|
|
|
|
|
ClinVar: RCV002264843
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Indian girl, born to consanguineous parents, with thiamine metabolism dysfunction syndrome-4 (THMD4; 613710), Gowda et al. (2019) identified a homozygous c.869T-A transversion in the SLC25A19 gene, resulting in a leu290-to-gln (L290Q) substitution. The mutation, which was identified with next generation sequencing and confirmed with Sanger sequencing, was found in the heterozygous state in both parents. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC25A19, GLY26ARG ({dbSNP rs181826033})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs181826033,
|
|
|
|
|
|
gnomAD: rs181826033,
|
|
|
|
|
|
ClinVar: RCV002264845
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Chinese sibs (patients 2 and 3) with thiamine metabolism dysfunction syndrome-4 (THMD4; 613710), Chen et al. (2021) identified compound heterozygous mutations in the SLC25A19 gene: a c.76G-A transition (c.76G-A, NM_001126122), resulting in a gly26-to-arg (G26R) substitution, and a c.745T-A transversion, resulting in a phe249-to-ile (F249I; 606521.0007) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were present in heterozygous state in the parents. The G26R mutation was present in the gnomAD database at a frequency of 0.0005 in the East Asian population. The F249I mutation was not present in the gnomAD database in the East Asian population. Transfection of each mutation into HEK293 cells resulted in deficient mitochondrial transport of thiamine pyrophosphate compared to wildtype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE)</strong>
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SLC25A19, PHE249ILE
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<br />
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SNP: rs1598180323,
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ClinVar: RCV002264844
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<span class="mim-text-font">
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<p>For discussion of the c.745T-A transversion (c.745T-A, NM_001126122) in the SLC25A19 gene, resulting in a phe249-to-ile (F249I) substitution, that was identified in compound heterozygous state in 2 Chinese sibs with thiamine metabolism dysfunction syndrome-4 (THMD4; 613710) by Chen et al. (2021), see 606521.0006. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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Bottega, R., Perrone, M. D., Vecchiato, K., Taddio, A., Sabui, S., Pecile, V., Said, H. M., Faletra, F.
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<strong>Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4.</strong>
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J. Hum. Genet. 64: 1075-1081, 2019.
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[PubMed: 31506564]
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[Full Text: https://doi.org/10.1038/s10038-019-0666-5]
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</li>
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<li>
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<p class="mim-text-font">
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Chen, Y., Fang, B., Hu, X., Guo, R., Guo, J., Fang, K., Ni, J., Li, W., Qian, S., Hao, C.
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<strong>Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.</strong>
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Orphanet J. Rare Dis. 16: 403, 2021.
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[PubMed: 34587972]
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[Full Text: https://doi.org/10.1186/s13023-021-02028-4]
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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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Dolce, V., Fiermonte, G., Runswick, M. J., Palmieri, F., Walker, J. E.
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<strong>The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals.</strong>
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Proc. Nat. Acad. Sci. 98: 2284-2288, 2001.
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[PubMed: 11226231]
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[Full Text: https://doi.org/10.1073/pnas.031430998]
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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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Gowda, V. K., Srinivasan, V. M., Jehta, K., Bhat, M. D.
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<strong>Bilateral striatal necrosis with polyneuropathy with a novel SLC25A19 (mitochondrial thiamine pyrophosphate carrier OMIM*606521) mutation: treatable thiamine metabolic disorder--a report of two Indian cases.</strong>
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Neuropediatrics 50: 313-317, 2019.
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[PubMed: 31295743]
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[Full Text: https://doi.org/10.1055/s-0039-1693148]
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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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Iacobazzi, V., Ventura, M., Fiermonte, G., Prezioso, G., Rocchi, M., Palmieri, F.
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<strong>Genomic organization and mapping of the gene (SLC25A19) encoding the human mitochondrial deoxynucleotide carrier (DNC).</strong>
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Cytogenet. Cell Genet. 93: 40-42, 2001.
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[PubMed: 11474176]
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[Full Text: https://doi.org/10.1159/000056945]
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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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Li, D., Song, J., Li, X., Liu, Y., Dong, H., Kang, L., Liu, Y., Zhang, Y., Jin, Y., Guan, H., Zhou, C., Yang, Y.
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<strong>Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome.</strong>
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Europ. J. Med. Genet. 63: 104003, 2020.
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[PubMed: 32679198]
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[Full Text: https://doi.org/10.1016/j.ejmg.2020.104003]
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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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Lindhurst, M. J., Fiermonte, G., Song, S., Struys, E., De Leonardis, F., Schwarzberg, P. L., Chen, A., Castegna, A., Verhoeven, N., Mathews, C. K., Palmieri, F., Biesecker, L. G.
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<strong>Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia.</strong>
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Proc. Nat. Acad. Sci. 103: 15927-15932, 2006.
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[PubMed: 17035501]
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[Full Text: https://doi.org/10.1073/pnas.0607661103]
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<p class="mim-text-font">
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Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G.
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<strong>Mutant deoxynucleotide carrier is associated with congenital microcephaly.</strong>
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Nature Genet. 32: 175-179, 2002.
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[PubMed: 12185364]
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[Full Text: https://doi.org/10.1038/ng948]
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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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Samur, B. M., Gumus, G., Canpolat, M., Gumus, H., Per, H., Caglayan, A. O.
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<strong>Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature.</strong>
|
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Clin. Dysmorph. 31: 125-131, 2022.
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[PubMed: 35102031]
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[Full Text: https://doi.org/10.1097/MCD.0000000000000411]
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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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Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O.
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<strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong>
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Ann. Neurol. 66: 419-424, 2009.
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[PubMed: 19798730]
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[Full Text: https://doi.org/10.1002/ana.21752]
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</p>
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</li>
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</ol>
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Contributors:
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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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Hilary J. Vernon - updated : 08/26/2022<br>Hilary J. Vernon - updated : 07/08/2022<br>Cassandra L. Kniffin - updated : 2/8/2012<br>Cassandra L. Kniffin - updated : 1/24/2011<br>Cassandra L. Kniffin - updated : 11/9/2006<br>Victor A. McKusick - updated : 8/29/2002
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</span>
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<span class="mim-text-font">
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Paul J. Converse : 11/30/2001
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carol : 08/26/2022<br>carol : 07/11/2022<br>carol : 07/08/2022<br>carol : 02/10/2012<br>ckniffin : 2/8/2012<br>wwang : 2/16/2011<br>ckniffin : 1/24/2011<br>carol : 9/22/2009<br>wwang : 11/20/2006<br>ckniffin : 11/9/2006<br>tkritzer : 9/6/2002<br>tkritzer : 9/3/2002<br>terry : 8/29/2002<br>mgross : 11/30/2001
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