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Entry
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- *300356 - TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 8A; TIMM8A
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- OMIM
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<p>
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<span class="h4">*300356</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<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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<a href="#geneStructure">Gene Structure</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/300356">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 role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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=ENSG00000126953;t=ENST00000372902" 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=1678" 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=300356" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000126953;t=ENST00000372902" 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_001145951,NM_004085" 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_004085" 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=300356" 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=02287&isoform_id=02287_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/TIMM8A" 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/3123843,4758152,6014944,13937789,15929312,47682895,119623258,119623259,189053247,225543159" 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/O60220" 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 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=1678" 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=ENSG00000126953;t=ENST00000372902" 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=TIMM8A" 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=TIMM8A" 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+1678" 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/TIMM8A" 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:1678" 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/1678" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chrX&hgg_gene=ENST00000372902.4&hgg_start=101345661&hgg_end=101348742&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 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:11817" 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:11817" 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/timm8a" 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=300356[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=300356[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/ENSG00000126953" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.gwascentral.org/search?q=TIMM8A" 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=TIMM8A" 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=TIMM8A&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/PA36523" 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:11817" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1353433" 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/TIMM8A#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:1353433" 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/1678/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=1678" 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=WBGene00000941;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-040801-158" 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=TIMM8A&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> 702423009<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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300356
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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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TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 8A; TIMM8A
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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>
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<h4>
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<span class="mim-font">
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|
TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 8, YEAST, HOMOLOG OF, A<br />
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DEAFNESS/DYSTONIA PEPTIDE; DDP<br />
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|
DEAFNESS/DYSTONIA PEPTIDE 1; DDP1<br />
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|
DFN1, 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>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TIMM8A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TIMM8A</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>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/X/499?start=-3&limit=10&highlight=499">Xq22.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:101345661-101348742&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">X:101,345,661-101,348,742</a> </span>
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</em>
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
|
<a href="/geneMap/X/499?start=-3&limit=10&highlight=499">
|
|
Xq22.1
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Mohr-Tranebjaerg syndrome
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/304700"> 304700 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/300356" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/300356" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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|
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<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
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</span>
|
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</span>
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<p>Using information from a patient with a 21-kb deletion in Xq22 and sensorineural deafness along with dystonia (Mohr-Tranebjaerg syndrome; MTS; <a href="/entry/304700">304700</a>), <a href="#4" class="mim-tip-reference" title="Jin, H., May, M., Tranebjaerg, L., Kendall, E., Fontan, G., Jackson, J., Subramony, S. H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C., Vetrie, D. <strong>A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness.</strong> Nature Genet. 14: 177-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841189</a>] [<a href="https://doi.org/10.1038/ng1096-177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841189">Jin et al. (1996)</a> characterized a novel transcript lying within the deletion region. This gene, which they named DDP (deafness/dystonia peptide), showed high levels of expression in fetal and adult brain. The DDP protein demonstrated striking similarity to a predicted S. pombe protein of no known function. Thus, it is likely that the DDP gene encodes an evolutionarily conserved novel polypeptide necessary for normal human neurologic development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8841189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Vetrie, D., Vorechovsky, I., Sideras, P., Holland, J., Davies, A., Flinter, F., Hammarstrom, L., Kinnon, C., Levinsky, R., Bobrow, M., Smith, C. I. E., Bentley, D. R. <strong>The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases.</strong> Nature 361: 226-233, 1993. Note: Erratum: Nature 364: 362 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8380905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8380905</a>] [<a href="https://doi.org/10.1038/361226a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8380905">Vetrie et al. (1993)</a> had described a patient with a deletion of the BTK gene (<a href="/entry/300300">300300</a>) that extended into a second gene, designated DXS1274E, lying 3-prime of BTK. This was the gene that was subsequently renamed DDP by <a href="#4" class="mim-tip-reference" title="Jin, H., May, M., Tranebjaerg, L., Kendall, E., Fontan, G., Jackson, J., Subramony, S. H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C., Vetrie, D. <strong>A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness.</strong> Nature Genet. 14: 177-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841189</a>] [<a href="https://doi.org/10.1038/ng1096-177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841189">Jin et al. (1996)</a>. The deduced DDP protein contains 97 amino acids and has a molecular mass of about 11 kD. DDP shows ubiquitous expression,with highest levels in fetal and adult brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8380905+8841189" 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 DDP gene contains 2 exons and an intron of approximately 2 kb (<a href="#16" class="mim-tip-reference" title="Vetrie, D., Vorechovsky, I., Sideras, P., Holland, J., Davies, A., Flinter, F., Hammarstrom, L., Kinnon, C., Levinsky, R., Bobrow, M., Smith, C. I. E., Bentley, D. R. <strong>The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases.</strong> Nature 361: 226-233, 1993. Note: Erratum: Nature 364: 362 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8380905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8380905</a>] [<a href="https://doi.org/10.1038/361226a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8380905">Vetrie et al., 1993</a>). The coding region spans both exons. The first exon of the cDNA sequence begins 770 bp downstream from the polyadenylation signal of BTK. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8380905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Koehler, C. M., Leuenberger, D., Merchant, S., Renold, A., Junne, T., Schatz, G. <strong>Human deafness dystonia syndrome is a mitochondrial disease.</strong> Proc. Nat. Acad. Sci. 96: 2141-2146, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051608[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.96.5.2141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051608">Koehler et al. (1999)</a> identified the function of the DDP gene. They demonstrated that DDP has similarity to 5 small mitochondrial proteins (Tim8p, Tim9p, Tim10p, Tim12p, and Tim13p) of the yeast mitochondrial intermembrane space. Tim9p, Tim10p, and Tim12p mediate the import of metabolite transporters from the cytoplasm into the mitochondrial inner membrane and interact structurally and functionally with Tim8p and Tim13p. DDP was found to be most similar to Tim8p. Tim8p exists as a soluble 70-kD complex with Tim13p and Tim9p, and deletion of Tim8p is synthetically lethal with a conditional mutation in Tim10p. <a href="#5" class="mim-tip-reference" title="Koehler, C. M., Leuenberger, D., Merchant, S., Renold, A., Junne, T., Schatz, G. <strong>Human deafness dystonia syndrome is a mitochondrial disease.</strong> Proc. Nat. Acad. Sci. 96: 2141-2146, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051608[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.96.5.2141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051608">Koehler et al. (1999)</a> concluded that the Mohr-Tranebjaerg syndrome is a novel type of mitochondrial disease that is most likely caused by a defective mitochondrial protein-import system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051608" 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="#8" class="mim-tip-reference" title="Roesch, K., Curran, S. P., Tranebjaerg, L., Koehler, C. M. <strong>Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex.</strong> Hum. Molec. Genet. 11: 477-486, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11875042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11875042</a>] [<a href="https://doi.org/10.1093/hmg/11.5.477" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11875042">Roesch et al. (2002)</a> showed that DDP1 assembles in a 70-kD complex in the intermembrane space with TIMM13 (<a href="/entry/607383">607383</a>). DDP1 was not detectable in fibroblasts derived from a Mohr-Tranebjaerg syndrome patient with the cys66-to-trp mutation (C66W; <a href="#0004">300356.0004</a>) in the twin CX3C motif of DDP1, in which 2 cysteine residues are separated by 3 amino acids. The corresponding mutation in yeast Tim8p yielded an unstable protein that did not assemble with yeast Tim13p. DDP1 restored Tim23p import when expressed with TIMM13 in yeast mitochondria lacking the Tim8p-Tim13p complex, and DDP1 and TIMM13 could be crosslinked to the human TIMM23 (<a href="/entry/605034">605034</a>) import intermediate in rat and yeast mitochondria. In a similar manner to Tim8p, DDP1 mediated the import of human TIMM23. The authors hypothesized that MTS may be caused by decreased levels of TIMM23 in the mitochondrial inner membrane in affected tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11875042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Roesch, K., Hynds, P. J., Varga, R., Tranebjaerg, L., Koehler, C. M. <strong>The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex.</strong> Hum. Molec. Genet. 13: 2101-2111, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15254020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15254020</a>] [<a href="https://doi.org/10.1093/hmg/ddh217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15254020">Roesch et al. (2004)</a> determined that citrin (SLC25A13; <a href="/entry/603859">603859</a>) and aralar (SLC25A12; <a href="/entry/603667">603667</a>), which are Ca(2+)-binding aspartate/glutamate carriers (AGC) of the mitochondrial inner membrane, are substrates for the TIMM8A/TIMM13 complex.. The AGCs function in the aspartate-malate NADH shuttle that moves reducing equivalents from the cytosol to the mitochondrial matrix. A lymphoblast cell line derived from an MTS patient had decreased NADH levels and defects in mitochondrial protein import. Protein expression studies indicated that DDP1 and TIMM13 showed nonuniform expression in mammals, and expression was prominent in the large neurons in the brain, which is in agreement with the expression pattern of SLC25A12. <a href="#9" class="mim-tip-reference" title="Roesch, K., Hynds, P. J., Varga, R., Tranebjaerg, L., Koehler, C. M. <strong>The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex.</strong> Hum. Molec. Genet. 13: 2101-2111, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15254020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15254020</a>] [<a href="https://doi.org/10.1093/hmg/ddh217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15254020">Roesch et al. (2004)</a> hypothesized that insufficient NADH shuttling, linked with changes in Ca(2+) concentration, in sensitive cells of the CNS might contribute to the pathologic process associated with MTS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15254020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Mohr-Tranebjaerg Syndrome</em></strong></p><p>
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In the original Norwegian family with Mohr-Tranebjaerg syndrome (MTS; <a href="/entry/304700">304700</a>) reported by <a href="#6" class="mim-tip-reference" title="Mohr, J., Mageroy, K. <strong>Sex-linked deafness of a possibly new type.</strong> Acta Genet. Statist. Med. 10: 54-62, 1960.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13771732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13771732</a>] [<a href="https://doi.org/10.1159/000151118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13771732">Mohr and Mageroy (1960)</a> and studied by <a href="#13" class="mim-tip-reference" title="Tranebjaerg, L., Schwartz, C., Eriksen, H., Andreasson, S., Ponjavic, V., Dahl, A., Stevenson, R. E., May, M., Arena, F., Barker, D., Elverland, H. H., Lubs, H. <strong>A new X linked recessive deafness syndrome with blindness, dystonia, fractures, and mental deficiency is linked to Xq22.</strong> J. Med. Genet. 32: 257-263, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7643352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7643352</a>] [<a href="https://doi.org/10.1136/jmg.32.4.257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7643352">Tranebjaerg et al. (1995)</a>, <a href="#4" class="mim-tip-reference" title="Jin, H., May, M., Tranebjaerg, L., Kendall, E., Fontan, G., Jackson, J., Subramony, S. H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C., Vetrie, D. <strong>A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness.</strong> Nature Genet. 14: 177-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841189</a>] [<a href="https://doi.org/10.1038/ng1096-177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841189">Jin et al. (1996)</a> demonstrated that affected males carried a 1-bp deletion in exon 1 of the DDP gene (151delT; <a href="#0001">300356.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7643352+13771732+8841189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Tranebjaerg, L., Hamel, B. C. J., Gabreels, F. J. M., Renier, W. O., Van Ghelue, M. <strong>A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness-dystonia-optic atrophy syndrome.</strong> Europ. J. Hum. Genet. 8: 464-467, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10878669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10878669</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200483" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10878669">Tranebjaerg et al. (2000)</a> reported the first de novo mutation in the DDP gene in an 11-year-old Dutch boy with deafness and dystonia. Previously reported mutations had all been frameshifts/nonsense mutations or deletion of the entire gene as part of a larger deletion encompassing also the BTK gene. In this case, a missense mutation (C66W) caused an equally severe clinical picture. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10878669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Tranebjaerg, L., van Ghelue, M., Nilssen, O., Hodes, M. E., Dlouhy, S. R., Farlow, M. R., Hamel, B., Arts, W. F. M., Jankovic, J., Beach, J., Jensen, P. K. A. <strong>Jensen syndrome is allelic to Mohr-Tranebjaerg syndrome and both are caused by stop mutations in the DDP gene. (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A349 only, 1997."None>Tranebjaerg et al. (1997)</a> demonstrated a nonsense mutation (E24X; <a href="#0003">300356.0003</a>) in the DDP gene in a male who was originally thought to have a distinct disorder called Jensen syndrome. The patient's nephew was found to have the same nonsense mutation and the disorder was considered the same as MTS (<a href="#12" class="mim-tip-reference" title="Tranebjaerg, L., Jensen, P. K. A., Van Ghelue, M., Vnencak-Jones, C. L., Sund, S., Elgjo, K., Jakobsen, J., Lindal, S., Warburg, M., Fuglsang-Frederiksen, A., Skullerud, K. <strong>Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene.</strong> Ophthalmic Genet. 22: 207-223, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11803487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11803487</a>] [<a href="https://doi.org/10.1076/opge.22.4.207.2220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11803487">Tranebjaerg et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11803487" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Hofmann, S., Rothbauer, U., Muhlenbein, N., Neupert, W., Gerbitz, K.-D., Brunner, M., Bauer, M. F. <strong>The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation of functional DDP1-TIM13 complexes in the mitochondrial intermembrane space.</strong> J. Biol. Chem. 277: 23287-23293, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11956200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11956200</a>] [<a href="https://doi.org/10.1074/jbc.M201154200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11956200">Hofmann et al. (2002)</a> transfected human TIMM8A carrying the C66W mutation into yeast cells and determined that the mutation did not effect expression of TIMM8A within the mitochondrial intermembrane space. The mutation did, however, produce an inactive protein that could not support mitochondrial import of proteins when coexpressed with its partner, TIMM13. Using binding, cross-linking, and biochemical studies of in vitro translated and recombinant human TIMM8A, <a href="#3" class="mim-tip-reference" title="Hofmann, S., Rothbauer, U., Muhlenbein, N., Neupert, W., Gerbitz, K.-D., Brunner, M., Bauer, M. F. <strong>The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation of functional DDP1-TIM13 complexes in the mitochondrial intermembrane space.</strong> J. Biol. Chem. 277: 23287-23293, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11956200/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11956200</a>] [<a href="https://doi.org/10.1074/jbc.M201154200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11956200">Hofmann et al. (2002)</a> found that the C66W mutation impaired the binding of Zn(2+) via the cys(4) zinc-binding motif. As a consequence, the mutated protein was incorrectly folded and lost its ability to assemble into heterohexameric 70-kD complexes with TIMM13. The mutant protein was also destabilized and was susceptible to enhanced proteolytic degradation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11956200" 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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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>9 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300356[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs869320664 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869320664;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=rs869320664" 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=rs869320664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012070" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012070" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012070</a>
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<p>In the original Norwegian family with Mohr-Tranebjaerg syndrome (MTS; <a href="/entry/304700">304700</a>), <a href="#4" class="mim-tip-reference" title="Jin, H., May, M., Tranebjaerg, L., Kendall, E., Fontan, G., Jackson, J., Subramony, S. H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C., Vetrie, D. <strong>A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness.</strong> Nature Genet. 14: 177-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841189</a>] [<a href="https://doi.org/10.1038/ng1096-177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841189">Jin et al. (1996)</a> demonstrated that affected males carried a 1-bp deletion in exon 1 (151delT). The consequent frameshift resulted in the incorporation of 25 novel amino acids after the glutamic acid at codon 38, followed by polypeptide termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8841189" 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">rs869320733 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869320733;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=rs869320733" 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=rs869320733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In pedigree K8190 segregating for sensorineural deafness and dystonia (MTS; <a href="/entry/304700">304700</a>) and the symptom of mental deficiency, <a href="#4" class="mim-tip-reference" title="Jin, H., May, M., Tranebjaerg, L., Kendall, E., Fontan, G., Jackson, J., Subramony, S. H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C., Vetrie, D. <strong>A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness.</strong> Nature Genet. 14: 177-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841189</a>] [<a href="https://doi.org/10.1038/ng1096-177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841189">Jin et al. (1996)</a> found a 10-bp deletion in exon 2 of the DDP gene. This mutation created a frameshift that resulted in the addition of 12 novel amino acids after the methionine residue at codon 48, followed by polypeptide termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8841189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs111033631 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033631;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/rs111033631?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=rs111033631" 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=rs111033631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012072" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012072" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012072</a>
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<p>In a patient with Mohr-Tranebjaerg syndrome (MTS; <a href="/entry/304700">304700</a>) from the original Dutch family thought to have a distinct disorder called Jensen syndrome, <a href="#14" class="mim-tip-reference" title="Tranebjaerg, L., van Ghelue, M., Nilssen, O., Hodes, M. E., Dlouhy, S. R., Farlow, M. R., Hamel, B., Arts, W. F. M., Jankovic, J., Beach, J., Jensen, P. K. A. <strong>Jensen syndrome is allelic to Mohr-Tranebjaerg syndrome and both are caused by stop mutations in the DDP gene. (Abstract)</strong> Am. J. Hum. Genet. 61 (suppl.): A349 only, 1997."None>Tranebjaerg et al. (1997)</a> identified a G-to-T transversion in exon 1 of the TIMM8A gene, resulting in a glu24-to-ter (E24X) substitution. <a href="#12" class="mim-tip-reference" title="Tranebjaerg, L., Jensen, P. K. A., Van Ghelue, M., Vnencak-Jones, C. L., Sund, S., Elgjo, K., Jakobsen, J., Lindal, S., Warburg, M., Fuglsang-Frederiksen, A., Skullerud, K. <strong>Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene.</strong> Ophthalmic Genet. 22: 207-223, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11803487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11803487</a>] [<a href="https://doi.org/10.1076/opge.22.4.207.2220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11803487">Tranebjaerg et al. (2001)</a> identified the same mutation in the patient's 21-year-old nephew. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11803487" 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">rs80356560 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356560;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=rs80356560" 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=rs80356560" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012073" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012073" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012073</a>
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<p><a href="#11" class="mim-tip-reference" title="Tranebjaerg, L., Hamel, B. C. J., Gabreels, F. J. M., Renier, W. O., Van Ghelue, M. <strong>A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness-dystonia-optic atrophy syndrome.</strong> Europ. J. Hum. Genet. 8: 464-467, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10878669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10878669</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200483" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10878669">Tranebjaerg et al. (2000)</a> identified a de novo mutation in the DDP gene in an 11-year-old Dutch boy with deafness and dystonia (MTS; <a href="/entry/304700">304700</a>). Whereas previously reported mutations had all been frameshifts/nonsense mutations or deletion of the entire gene, this was a missense mutation, cys66 to trp (C66W). This mutation caused an equally severe clinical picture. Sensorineural hearing impairment had been diagnosed at the age of 2.5 years; mild mental retardation and normal behavior were present. He was toilet-trained during the daytime by age 4. Although at the age of 3 years neurologic examination was normal, at ages 5 to 6 years he had lost skills such as drawing, playing with puppets, and similar tasks. From age 10, he had abnormal posture and trembling of the left hand, and increasing difficulties with tying his shoelaces and his belt. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10878669" 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 MOHR-TRANEBJAERG SYNDROME</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs869320665 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869320665;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=rs869320665" 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=rs869320665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012074 OR RCV003556003" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012074, RCV003556003" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012074...</a>
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<p>In a family with Mohr-Tranebjaerg syndrome (MTS; <a href="/entry/304700">304700</a>), <a href="#10" class="mim-tip-reference" title="Swerdlow, R. H., Wooten, G. F. <strong>A novel deafness/dystonia peptide gene mutation that causes dystonia in female carriers of Mohr-Tranebjaerg syndrome.</strong> Ann. Neurol. 50: 537-540, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11601506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11601506</a>] [<a href="https://doi.org/10.1002/ana.1160" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11601506">Swerdlow and Wooten (2001)</a> found that affected members had deletion of guanine-108 of the TIMM8A gene, which terminated the 97-amino acid protein at codon 25. Unlike previously reported kindreds, carrier females in this family also manifested dystonias, including torticollis and writer's cramp. At 28 years, the proband developed progressively worsening involuntary head and neck movements. Generalized dystonia and a markedly hypertrophied right sternocleidomastoid were present. Intermittent, involuntary contractions of the right sternocleidomastoid flexed his right ear onto his shoulder. Muscle tone was normal between paroxysms of dystonic contractions. The proband's mother had head shaking, chronic muscle pain, and writer's cramp beginning at age 25 years. The sister of the proband had onset of head shaking in her late teens and writer's cramp in her mid-twenties. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11601506" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012075" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012075" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012075</a>
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<p>In a patient with sensorineural deafness and dystonia (MTS; <a href="/entry/304700">304700</a>), <a href="#4" class="mim-tip-reference" title="Jin, H., May, M., Tranebjaerg, L., Kendall, E., Fontan, G., Jackson, J., Subramony, S. H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C., Vetrie, D. <strong>A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness.</strong> Nature Genet. 14: 177-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841189</a>] [<a href="https://doi.org/10.1038/ng1096-177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841189">Jin et al. (1996)</a> found a 21-kb deletion in Xq22, resulting in deletion of the entire TIMM8A gene. The patient also suffered from X-linked agammaglobulinemia, caused by mutation in the neighboring BTK gene (<a href="/entry/300300">300300</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8841189" 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="Pizzuti, A., Fabbrini, G., Salehi, L., Vacca, L., Inghilleri, M., Dallapiccola, B., Berardelli, A. <strong>Focal dystonia caused by Mohr-Tranebjaerg syndrome with complete deletion of the DDP1 gene.</strong> Neurology 62: 1021-1022, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037720</a>] [<a href="https://doi.org/10.1212/01.wnl.0000115174.96423.a8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15037720">Pizzuti et al. (2004)</a> reported a 24-year-old man diagnosed at age 2 years with Bruton agammaglobulinemia and bilateral hearing loss. He later developed progressive visual loss at age 15 and progressive writing difficulties due to focal dystonia at age 19. The mild clinical features were unique in that the dystonia appeared late in life and was task specific, and he had only mild cognitive impairment. Molecular analysis detected complete deletion of the DDP1 gene and partial deletion of the BTK gene. <a href="#7" class="mim-tip-reference" title="Pizzuti, A., Fabbrini, G., Salehi, L., Vacca, L., Inghilleri, M., Dallapiccola, B., Berardelli, A. <strong>Focal dystonia caused by Mohr-Tranebjaerg syndrome with complete deletion of the DDP1 gene.</strong> Neurology 62: 1021-1022, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037720</a>] [<a href="https://doi.org/10.1212/01.wnl.0000115174.96423.a8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15037720">Pizzuti et al. (2004)</a> suggested that complete absence of the DDP1 protein may result in less significant effects on the mitochondrial multiprotein complex than truncated DDP1 peptides, which may disrupt the multiprotein complex and cause more severe clinical manifestations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15037720" 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">rs1054894 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1054894;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=rs1054894" 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=rs1054894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012076" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012076" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012076</a>
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<p>In affected members of a Japanese family with Mohr-Tranebjaerg syndrome (MTS; <a href="/entry/304700">304700</a>), <a href="#15" class="mim-tip-reference" title="Ujike, H., Tanabe, Y., Takehisa, Y., Hayabara, T., Kuroda, S. <strong>A family with X-linked dystonia-deafness syndrome with a novel mutation of the DDP gene.</strong> Arch. Neurol. 58: 1004-1007, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11405816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11405816</a>] [<a href="https://doi.org/10.1001/archneur.58.6.1004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11405816">Ujike et al. (2001)</a> identified a nonsense mutation, arg80-to-ter, in the TIMM8A gene, resulting in a truncated protein of 79 amino acids. The authors noted that this truncated protein is longer than that reported in other mutations and postulated that the longer amino acid sequence could be related to the milder clinical symptoms and slower progression in this Japanese family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11405816" 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">rs869320666 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869320666;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=rs869320666" 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=rs869320666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012077" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012077" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012077</a>
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<p>In 2 affected members of a Spanish family with Mohr-Tranebjaerg syndrome (MTS; <a href="/entry/304700">304700</a>), <a href="#2" class="mim-tip-reference" title="Ezquerra, M., Campdelacreu, J., Munoz, E., Tolosa, E., Marti, M. J. <strong>A novel intronic mutation in the DDP1 gene in a family with X-linked dystonia-deafness syndrome.</strong> Arch. Neurol. 62: 306-308, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15710860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15710860</a>] [<a href="https://doi.org/10.1001/archneur.62.2.306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15710860">Ezquerra et al. (2005)</a> identified an A-to-C transversion at position -23 in intron 1 of the TIMM8A gene, referenced to the first nucleotide of exon 2 (IVS1-23A-C). The mutation is predicted to result in a splicing defect. One of the patients had onset at age 4 years, complete hearing loss, severe generalized dystonia, and loss of vision, whereas the other patient had onset at 11 years, mild hearing loss, mild focal dystonia, and behavioral disturbances. The patients' mothers and aunt were heterozygous for the mutation. The mutation was not identified in 90 control individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15710860" 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">rs869320667 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869320667;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=rs869320667" 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=rs869320667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012078" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012078" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012078</a>
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<p>In 2 Spanish brothers with Mohr-Tranebjaerg syndrome (MTS; <a href="/entry/304700">304700</a>), <a href="#1" class="mim-tip-reference" title="Aguirre, L. A., del Castillo, I., Macaya, A., Meda, C., Villamar, M., Moreno-Pelayo, M. A., Moreno, F. <strong>A novel mutation in the gene encoding TIMM8a, a component of the mitochondrial protein translocase complexes, in a Spanish familial case of deafness-dystonia (Mohr-Tranebjaerg) syndrome.</strong> Am. J. Med. Genet. 140A: 392-397, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16411215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16411215</a>] [<a href="https://doi.org/10.1002/ajmg.a.31079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16411215">Aguirre et al. (2006)</a> identified a 1-bp deletion (127delT) in the TIMM8A gene, resulting in a frameshift and premature stop codon at residue 64. Their unaffected mother was heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16411215" 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>A novel mutation in the gene encoding TIMM8a, a component of the mitochondrial protein translocase complexes, in a Spanish familial case of deafness-dystonia (Mohr-Tranebjaerg) syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16411215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16411215</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16411215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.31079" target="_blank">Full Text</a>]
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<strong>A novel intronic mutation in the DDP1 gene in a family with X-linked dystonia-deafness syndrome.</strong>
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[<a href="https://doi.org/10.1001/archneur.62.2.306" target="_blank">Full Text</a>]
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<strong>The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation of functional DDP1-TIM13 complexes in the mitochondrial intermembrane space.</strong>
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[<a href="https://doi.org/10.1074/jbc.M201154200" target="_blank">Full Text</a>]
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Jin, H., May, M., Tranebjaerg, L., Kendall, E., Fontan, G., Jackson, J., Subramony, S. H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C., Vetrie, D.
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[<a href="https://doi.org/10.1038/ng1096-177" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.96.5.2141" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000151118" target="_blank">Full Text</a>]
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<strong>Focal dystonia caused by Mohr-Tranebjaerg syndrome with complete deletion of the DDP1 gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037720</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15037720" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000115174.96423.a8" target="_blank">Full Text</a>]
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<strong>Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex.</strong>
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Hum. Molec. Genet. 11: 477-486, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11875042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11875042</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11875042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/11.5.477" target="_blank">Full Text</a>]
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Roesch, K., Hynds, P. J., Varga, R., Tranebjaerg, L., Koehler, C. M.
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<strong>The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex.</strong>
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Hum. Molec. Genet. 13: 2101-2111, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15254020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15254020</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15254020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddh217" target="_blank">Full Text</a>]
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<a id="Swerdlow2001" class="mim-anchor"></a>
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Swerdlow, R. H., Wooten, G. F.
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<strong>A novel deafness/dystonia peptide gene mutation that causes dystonia in female carriers of Mohr-Tranebjaerg syndrome.</strong>
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Ann. Neurol. 50: 537-540, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11601506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11601506</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11601506" 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.1160" target="_blank">Full Text</a>]
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<a id="Tranebjaerg2000" class="mim-anchor"></a>
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Tranebjaerg, L., Hamel, B. C. J., Gabreels, F. J. M., Renier, W. O., Van Ghelue, M.
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<strong>A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness-dystonia-optic atrophy syndrome.</strong>
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Europ. J. Hum. Genet. 8: 464-467, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10878669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10878669</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10878669" 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/sj.ejhg.5200483" target="_blank">Full Text</a>]
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Tranebjaerg, L., Jensen, P. K. A., Van Ghelue, M., Vnencak-Jones, C. L., Sund, S., Elgjo, K., Jakobsen, J., Lindal, S., Warburg, M., Fuglsang-Frederiksen, A., Skullerud, K.
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<strong>Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11803487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11803487</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11803487" 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/10.1076/opge.22.4.207.2220" target="_blank">Full Text</a>]
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Tranebjaerg, L., Schwartz, C., Eriksen, H., Andreasson, S., Ponjavic, V., Dahl, A., Stevenson, R. E., May, M., Arena, F., Barker, D., Elverland, H. H., Lubs, H.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7643352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7643352</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7643352" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.32.4.257" target="_blank">Full Text</a>]
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Tranebjaerg, L., van Ghelue, M., Nilssen, O., Hodes, M. E., Dlouhy, S. R., Farlow, M. R., Hamel, B., Arts, W. F. M., Jankovic, J., Beach, J., Jensen, P. K. A.
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Ujike, H., Tanabe, Y., Takehisa, Y., Hayabara, T., Kuroda, S.
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<strong>A family with X-linked dystonia-deafness syndrome with a novel mutation of the DDP gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11405816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11405816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11405816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1001/archneur.58.6.1004" target="_blank">Full Text</a>]
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Vetrie, D., Vorechovsky, I., Sideras, P., Holland, J., Davies, A., Flinter, F., Hammarstrom, L., Kinnon, C., Levinsky, R., Bobrow, M., Smith, C. I. E., Bentley, D. R.
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<strong>The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8380905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8380905</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8380905" 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/10.1038/361226a0" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Carol A. Bocchini - updated : 4/20/2016
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George E. Tiller - updated : 3/21/2007<br>Cassandra L. Kniffin - updated : 2/28/2006<br>Cassandra L. Kniffin - updated : 7/6/2005<br>Cassandra L. Kniffin - updated : 6/28/2005<br>Patricia A. Hartz - updated : 10/28/2002<br>George E. Tiller - updated : 10/7/2002<br>Cassandra L. Kniffin - updated : 9/27/2002<br>Cassandra L. Kniffin - updated : 8/23/2002<br>Victor A. McKusick - updated : 12/5/2001
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</span>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh : 8/24/2001
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</span>
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</div>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 12/17/2019
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/20/2016<br>carol : 4/20/2016<br>carol : 4/14/2016<br>terry : 10/3/2012<br>wwang : 7/2/2008<br>wwang : 3/23/2007<br>terry : 3/21/2007<br>carol : 2/8/2007<br>wwang : 3/16/2006<br>ckniffin : 2/28/2006<br>wwang : 7/11/2005<br>ckniffin : 7/6/2005<br>wwang : 6/29/2005<br>ckniffin : 6/28/2005<br>mgross : 12/2/2002<br>mgross : 10/28/2002<br>cwells : 10/7/2002<br>carol : 9/27/2002<br>ckniffin : 9/27/2002<br>carol : 8/27/2002<br>carol : 8/26/2002<br>ckniffin : 8/23/2002<br>carol : 3/19/2002<br>alopez : 1/30/2002<br>alopez : 12/7/2001<br>terry : 12/5/2001<br>carol : 8/24/2001<br>carol : 8/24/2001<br>carol : 8/24/2001
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 300356
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 8A; TIMM8A
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 8, YEAST, HOMOLOG OF, A<br />
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DEAFNESS/DYSTONIA PEPTIDE; DDP<br />
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DEAFNESS/DYSTONIA PEPTIDE 1; DDP1<br />
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DFN1, FORMERLY
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</span>
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</h4>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TIMM8A</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 702423009;
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</span>
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</p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: Xq22.1
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Genomic coordinates <span class="small">(GRCh38)</span> : X:101,345,661-101,348,742 </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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</p>
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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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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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Xq22.1
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</span>
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<td>
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<span class="mim-font">
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Mohr-Tranebjaerg syndrome
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</span>
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</td>
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<td>
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<span class="mim-font">
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304700
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</td>
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<td>
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<span class="mim-font">
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X-linked recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>TIMM8A belongs to a family of evolutionary conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using information from a patient with a 21-kb deletion in Xq22 and sensorineural deafness along with dystonia (Mohr-Tranebjaerg syndrome; MTS; 304700), Jin et al. (1996) characterized a novel transcript lying within the deletion region. This gene, which they named DDP (deafness/dystonia peptide), showed high levels of expression in fetal and adult brain. The DDP protein demonstrated striking similarity to a predicted S. pombe protein of no known function. Thus, it is likely that the DDP gene encodes an evolutionarily conserved novel polypeptide necessary for normal human neurologic development. </p><p>Vetrie et al. (1993) had described a patient with a deletion of the BTK gene (300300) that extended into a second gene, designated DXS1274E, lying 3-prime of BTK. This was the gene that was subsequently renamed DDP by Jin et al. (1996). The deduced DDP protein contains 97 amino acids and has a molecular mass of about 11 kD. DDP shows ubiquitous expression,with highest levels in fetal and adult brain. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The DDP gene contains 2 exons and an intron of approximately 2 kb (Vetrie et al., 1993). The coding region spans both exons. The first exon of the cDNA sequence begins 770 bp downstream from the polyadenylation signal of BTK. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Koehler et al. (1999) identified the function of the DDP gene. They demonstrated that DDP has similarity to 5 small mitochondrial proteins (Tim8p, Tim9p, Tim10p, Tim12p, and Tim13p) of the yeast mitochondrial intermembrane space. Tim9p, Tim10p, and Tim12p mediate the import of metabolite transporters from the cytoplasm into the mitochondrial inner membrane and interact structurally and functionally with Tim8p and Tim13p. DDP was found to be most similar to Tim8p. Tim8p exists as a soluble 70-kD complex with Tim13p and Tim9p, and deletion of Tim8p is synthetically lethal with a conditional mutation in Tim10p. Koehler et al. (1999) concluded that the Mohr-Tranebjaerg syndrome is a novel type of mitochondrial disease that is most likely caused by a defective mitochondrial protein-import system. </p><p>Roesch et al. (2002) showed that DDP1 assembles in a 70-kD complex in the intermembrane space with TIMM13 (607383). DDP1 was not detectable in fibroblasts derived from a Mohr-Tranebjaerg syndrome patient with the cys66-to-trp mutation (C66W; 300356.0004) in the twin CX3C motif of DDP1, in which 2 cysteine residues are separated by 3 amino acids. The corresponding mutation in yeast Tim8p yielded an unstable protein that did not assemble with yeast Tim13p. DDP1 restored Tim23p import when expressed with TIMM13 in yeast mitochondria lacking the Tim8p-Tim13p complex, and DDP1 and TIMM13 could be crosslinked to the human TIMM23 (605034) import intermediate in rat and yeast mitochondria. In a similar manner to Tim8p, DDP1 mediated the import of human TIMM23. The authors hypothesized that MTS may be caused by decreased levels of TIMM23 in the mitochondrial inner membrane in affected tissues. </p><p>Roesch et al. (2004) determined that citrin (SLC25A13; 603859) and aralar (SLC25A12; 603667), which are Ca(2+)-binding aspartate/glutamate carriers (AGC) of the mitochondrial inner membrane, are substrates for the TIMM8A/TIMM13 complex.. The AGCs function in the aspartate-malate NADH shuttle that moves reducing equivalents from the cytosol to the mitochondrial matrix. A lymphoblast cell line derived from an MTS patient had decreased NADH levels and defects in mitochondrial protein import. Protein expression studies indicated that DDP1 and TIMM13 showed nonuniform expression in mammals, and expression was prominent in the large neurons in the brain, which is in agreement with the expression pattern of SLC25A12. Roesch et al. (2004) hypothesized that insufficient NADH shuttling, linked with changes in Ca(2+) concentration, in sensitive cells of the CNS might contribute to the pathologic process associated with MTS. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Mohr-Tranebjaerg Syndrome</em></strong></p><p>
|
|
In the original Norwegian family with Mohr-Tranebjaerg syndrome (MTS; 304700) reported by Mohr and Mageroy (1960) and studied by Tranebjaerg et al. (1995), Jin et al. (1996) demonstrated that affected males carried a 1-bp deletion in exon 1 of the DDP gene (151delT; 300356.0001). </p><p>Tranebjaerg et al. (2000) reported the first de novo mutation in the DDP gene in an 11-year-old Dutch boy with deafness and dystonia. Previously reported mutations had all been frameshifts/nonsense mutations or deletion of the entire gene as part of a larger deletion encompassing also the BTK gene. In this case, a missense mutation (C66W) caused an equally severe clinical picture. </p><p>Tranebjaerg et al. (1997) demonstrated a nonsense mutation (E24X; 300356.0003) in the DDP gene in a male who was originally thought to have a distinct disorder called Jensen syndrome. The patient's nephew was found to have the same nonsense mutation and the disorder was considered the same as MTS (Tranebjaerg et al., 2001). </p><p>Hofmann et al. (2002) transfected human TIMM8A carrying the C66W mutation into yeast cells and determined that the mutation did not effect expression of TIMM8A within the mitochondrial intermembrane space. The mutation did, however, produce an inactive protein that could not support mitochondrial import of proteins when coexpressed with its partner, TIMM13. Using binding, cross-linking, and biochemical studies of in vitro translated and recombinant human TIMM8A, Hofmann et al. (2002) found that the C66W mutation impaired the binding of Zn(2+) via the cys(4) zinc-binding motif. As a consequence, the mutated protein was incorrectly folded and lost its ability to assemble into heterohexameric 70-kD complexes with TIMM13. The mutant protein was also destabilized and was susceptible to enhanced proteolytic degradation. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0001 MOHR-TRANEBJAERG SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM8A, 1-BP DEL, 151T
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<br />
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SNP: rs869320664,
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ClinVar: RCV000012070
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In the original Norwegian family with Mohr-Tranebjaerg syndrome (MTS; 304700), Jin et al. (1996) demonstrated that affected males carried a 1-bp deletion in exon 1 (151delT). The consequent frameshift resulted in the incorporation of 25 novel amino acids after the glutamic acid at codon 38, followed by polypeptide termination. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0002 MOHR-TRANEBJAERG SYNDROME</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM8A, 10-BP DEL, FS61TER
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<br />
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SNP: rs869320733,
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ClinVar: RCV000012071
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In pedigree K8190 segregating for sensorineural deafness and dystonia (MTS; 304700) and the symptom of mental deficiency, Jin et al. (1996) found a 10-bp deletion in exon 2 of the DDP gene. This mutation created a frameshift that resulted in the addition of 12 novel amino acids after the methionine residue at codon 48, followed by polypeptide termination. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 MOHR-TRANEBJAERG SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM8A, GLU24TER
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<br />
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SNP: rs111033631,
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gnomAD: rs111033631,
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ClinVar: RCV000012072
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with Mohr-Tranebjaerg syndrome (MTS; 304700) from the original Dutch family thought to have a distinct disorder called Jensen syndrome, Tranebjaerg et al. (1997) identified a G-to-T transversion in exon 1 of the TIMM8A gene, resulting in a glu24-to-ter (E24X) substitution. Tranebjaerg et al. (2001) identified the same mutation in the patient's 21-year-old nephew. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 MOHR-TRANEBJAERG SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM8A, CYS66TRP
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<br />
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SNP: rs80356560,
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ClinVar: RCV000012073
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Tranebjaerg et al. (2000) identified a de novo mutation in the DDP gene in an 11-year-old Dutch boy with deafness and dystonia (MTS; 304700). Whereas previously reported mutations had all been frameshifts/nonsense mutations or deletion of the entire gene, this was a missense mutation, cys66 to trp (C66W). This mutation caused an equally severe clinical picture. Sensorineural hearing impairment had been diagnosed at the age of 2.5 years; mild mental retardation and normal behavior were present. He was toilet-trained during the daytime by age 4. Although at the age of 3 years neurologic examination was normal, at ages 5 to 6 years he had lost skills such as drawing, playing with puppets, and similar tasks. From age 10, he had abnormal posture and trembling of the left hand, and increasing difficulties with tying his shoelaces and his belt. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 MOHR-TRANEBJAERG SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM8A, 1-BP DEL, 108G
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<br />
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SNP: rs869320665,
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ClinVar: RCV000012074, RCV003556003
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with Mohr-Tranebjaerg syndrome (MTS; 304700), Swerdlow and Wooten (2001) found that affected members had deletion of guanine-108 of the TIMM8A gene, which terminated the 97-amino acid protein at codon 25. Unlike previously reported kindreds, carrier females in this family also manifested dystonias, including torticollis and writer's cramp. At 28 years, the proband developed progressively worsening involuntary head and neck movements. Generalized dystonia and a markedly hypertrophied right sternocleidomastoid were present. Intermittent, involuntary contractions of the right sternocleidomastoid flexed his right ear onto his shoulder. Muscle tone was normal between paroxysms of dystonic contractions. The proband's mother had head shaking, chronic muscle pain, and writer's cramp beginning at age 25 years. The sister of the proband had onset of head shaking in her late teens and writer's cramp in her mid-twenties. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 MOHR-TRANEBJAERG SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM8A, DEL
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<br />
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ClinVar: RCV000012075
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with sensorineural deafness and dystonia (MTS; 304700), Jin et al. (1996) found a 21-kb deletion in Xq22, resulting in deletion of the entire TIMM8A gene. The patient also suffered from X-linked agammaglobulinemia, caused by mutation in the neighboring BTK gene (300300). </p><p>Pizzuti et al. (2004) reported a 24-year-old man diagnosed at age 2 years with Bruton agammaglobulinemia and bilateral hearing loss. He later developed progressive visual loss at age 15 and progressive writing difficulties due to focal dystonia at age 19. The mild clinical features were unique in that the dystonia appeared late in life and was task specific, and he had only mild cognitive impairment. Molecular analysis detected complete deletion of the DDP1 gene and partial deletion of the BTK gene. Pizzuti et al. (2004) suggested that complete absence of the DDP1 protein may result in less significant effects on the mitochondrial multiprotein complex than truncated DDP1 peptides, which may disrupt the multiprotein complex and cause more severe clinical manifestations. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 MOHR-TRANEBJAERG SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM8A, ARG80TER
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<br />
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SNP: rs1054894,
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ClinVar: RCV000012076
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a Japanese family with Mohr-Tranebjaerg syndrome (MTS; 304700), Ujike et al. (2001) identified a nonsense mutation, arg80-to-ter, in the TIMM8A gene, resulting in a truncated protein of 79 amino acids. The authors noted that this truncated protein is longer than that reported in other mutations and postulated that the longer amino acid sequence could be related to the milder clinical symptoms and slower progression in this Japanese family. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0008 MOHR-TRANEBJAERG SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM8A, IVS1, A-C, -23
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<br />
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SNP: rs869320666,
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ClinVar: RCV000012077
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 affected members of a Spanish family with Mohr-Tranebjaerg syndrome (MTS; 304700), Ezquerra et al. (2005) identified an A-to-C transversion at position -23 in intron 1 of the TIMM8A gene, referenced to the first nucleotide of exon 2 (IVS1-23A-C). The mutation is predicted to result in a splicing defect. One of the patients had onset at age 4 years, complete hearing loss, severe generalized dystonia, and loss of vision, whereas the other patient had onset at 11 years, mild hearing loss, mild focal dystonia, and behavioral disturbances. The patients' mothers and aunt were heterozygous for the mutation. The mutation was not identified in 90 control individuals. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0009 MOHR-TRANEBJAERG SYNDROME</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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TIMM8A, 1-BP DEL, 127T
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<br />
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SNP: rs869320667,
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ClinVar: RCV000012078
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 2 Spanish brothers with Mohr-Tranebjaerg syndrome (MTS; 304700), Aguirre et al. (2006) identified a 1-bp deletion (127delT) in the TIMM8A gene, resulting in a frameshift and premature stop codon at residue 64. Their unaffected mother was heterozygous for the mutation. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
|
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<p class="mim-text-font">
|
|
Aguirre, L. A., del Castillo, I., Macaya, A., Meda, C., Villamar, M., Moreno-Pelayo, M. A., Moreno, F.
|
|
<strong>A novel mutation in the gene encoding TIMM8a, a component of the mitochondrial protein translocase complexes, in a Spanish familial case of deafness-dystonia (Mohr-Tranebjaerg) syndrome.</strong>
|
|
Am. J. Med. Genet. 140A: 392-397, 2006.
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[PubMed: 16411215]
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[Full Text: https://doi.org/10.1002/ajmg.a.31079]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Ezquerra, M., Campdelacreu, J., Munoz, E., Tolosa, E., Marti, M. J.
|
|
<strong>A novel intronic mutation in the DDP1 gene in a family with X-linked dystonia-deafness syndrome.</strong>
|
|
Arch. Neurol. 62: 306-308, 2005.
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[PubMed: 15710860]
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[Full Text: https://doi.org/10.1001/archneur.62.2.306]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Hofmann, S., Rothbauer, U., Muhlenbein, N., Neupert, W., Gerbitz, K.-D., Brunner, M., Bauer, M. F.
|
|
<strong>The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation of functional DDP1-TIM13 complexes in the mitochondrial intermembrane space.</strong>
|
|
J. Biol. Chem. 277: 23287-23293, 2002.
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[PubMed: 11956200]
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[Full Text: https://doi.org/10.1074/jbc.M201154200]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Jin, H., May, M., Tranebjaerg, L., Kendall, E., Fontan, G., Jackson, J., Subramony, S. H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C., Vetrie, D.
|
|
<strong>A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness.</strong>
|
|
Nature Genet. 14: 177-180, 1996.
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[PubMed: 8841189]
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[Full Text: https://doi.org/10.1038/ng1096-177]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Koehler, C. M., Leuenberger, D., Merchant, S., Renold, A., Junne, T., Schatz, G.
|
|
<strong>Human deafness dystonia syndrome is a mitochondrial disease.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 2141-2146, 1999.
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[PubMed: 10051608]
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[Full Text: https://doi.org/10.1073/pnas.96.5.2141]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Mohr, J., Mageroy, K.
|
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<strong>Sex-linked deafness of a possibly new type.</strong>
|
|
Acta Genet. Statist. Med. 10: 54-62, 1960.
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[PubMed: 13771732]
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[Full Text: https://doi.org/10.1159/000151118]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Pizzuti, A., Fabbrini, G., Salehi, L., Vacca, L., Inghilleri, M., Dallapiccola, B., Berardelli, A.
|
|
<strong>Focal dystonia caused by Mohr-Tranebjaerg syndrome with complete deletion of the DDP1 gene.</strong>
|
|
Neurology 62: 1021-1022, 2004.
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[PubMed: 15037720]
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[Full Text: https://doi.org/10.1212/01.wnl.0000115174.96423.a8]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Roesch, K., Curran, S. P., Tranebjaerg, L., Koehler, C. M.
|
|
<strong>Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex.</strong>
|
|
Hum. Molec. Genet. 11: 477-486, 2002.
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[PubMed: 11875042]
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[Full Text: https://doi.org/10.1093/hmg/11.5.477]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Roesch, K., Hynds, P. J., Varga, R., Tranebjaerg, L., Koehler, C. M.
|
|
<strong>The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex.</strong>
|
|
Hum. Molec. Genet. 13: 2101-2111, 2004.
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|
|
[PubMed: 15254020]
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[Full Text: https://doi.org/10.1093/hmg/ddh217]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Swerdlow, R. H., Wooten, G. F.
|
|
<strong>A novel deafness/dystonia peptide gene mutation that causes dystonia in female carriers of Mohr-Tranebjaerg syndrome.</strong>
|
|
Ann. Neurol. 50: 537-540, 2001.
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[PubMed: 11601506]
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[Full Text: https://doi.org/10.1002/ana.1160]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Tranebjaerg, L., Hamel, B. C. J., Gabreels, F. J. M., Renier, W. O., Van Ghelue, M.
|
|
<strong>A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness-dystonia-optic atrophy syndrome.</strong>
|
|
Europ. J. Hum. Genet. 8: 464-467, 2000.
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[PubMed: 10878669]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5200483]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Tranebjaerg, L., Jensen, P. K. A., Van Ghelue, M., Vnencak-Jones, C. L., Sund, S., Elgjo, K., Jakobsen, J., Lindal, S., Warburg, M., Fuglsang-Frederiksen, A., Skullerud, K.
|
|
<strong>Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene.</strong>
|
|
Ophthalmic Genet. 22: 207-223, 2001.
|
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|
|
[PubMed: 11803487]
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|
[Full Text: https://doi.org/10.1076/opge.22.4.207.2220]
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Tranebjaerg, L., Schwartz, C., Eriksen, H., Andreasson, S., Ponjavic, V., Dahl, A., Stevenson, R. E., May, M., Arena, F., Barker, D., Elverland, H. H., Lubs, H.
|
|
<strong>A new X linked recessive deafness syndrome with blindness, dystonia, fractures, and mental deficiency is linked to Xq22.</strong>
|
|
J. Med. Genet. 32: 257-263, 1995.
|
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|
|
[PubMed: 7643352]
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[Full Text: https://doi.org/10.1136/jmg.32.4.257]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Tranebjaerg, L., van Ghelue, M., Nilssen, O., Hodes, M. E., Dlouhy, S. R., Farlow, M. R., Hamel, B., Arts, W. F. M., Jankovic, J., Beach, J., Jensen, P. K. A.
|
|
<strong>Jensen syndrome is allelic to Mohr-Tranebjaerg syndrome and both are caused by stop mutations in the DDP gene. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 61 (suppl.): A349 only, 1997.
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Ujike, H., Tanabe, Y., Takehisa, Y., Hayabara, T., Kuroda, S.
|
|
<strong>A family with X-linked dystonia-deafness syndrome with a novel mutation of the DDP gene.</strong>
|
|
Arch. Neurol. 58: 1004-1007, 2001.
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|
|
[PubMed: 11405816]
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[Full Text: https://doi.org/10.1001/archneur.58.6.1004]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Vetrie, D., Vorechovsky, I., Sideras, P., Holland, J., Davies, A., Flinter, F., Hammarstrom, L., Kinnon, C., Levinsky, R., Bobrow, M., Smith, C. I. E., Bentley, D. R.
|
|
<strong>The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases.</strong>
|
|
Nature 361: 226-233, 1993. Note: Erratum: Nature 364: 362 only, 1993.
|
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|
|
[PubMed: 8380905]
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[Full Text: https://doi.org/10.1038/361226a0]
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</p>
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</li>
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</ol>
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<div>
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<br />
|
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</div>
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</div>
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</div>
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<div>
|
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<div class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
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Carol A. Bocchini - updated : 4/20/2016<br>George E. Tiller - updated : 3/21/2007<br>Cassandra L. Kniffin - updated : 2/28/2006<br>Cassandra L. Kniffin - updated : 7/6/2005<br>Cassandra L. Kniffin - updated : 6/28/2005<br>Patricia A. Hartz - updated : 10/28/2002<br>George E. Tiller - updated : 10/7/2002<br>Cassandra L. Kniffin - updated : 9/27/2002<br>Cassandra L. Kniffin - updated : 8/23/2002<br>Victor A. McKusick - updated : 12/5/2001
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Ada Hamosh : 8/24/2001
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carol : 12/17/2019<br>carol : 04/20/2016<br>carol : 4/20/2016<br>carol : 4/14/2016<br>terry : 10/3/2012<br>wwang : 7/2/2008<br>wwang : 3/23/2007<br>terry : 3/21/2007<br>carol : 2/8/2007<br>wwang : 3/16/2006<br>ckniffin : 2/28/2006<br>wwang : 7/11/2005<br>ckniffin : 7/6/2005<br>wwang : 6/29/2005<br>ckniffin : 6/28/2005<br>mgross : 12/2/2002<br>mgross : 10/28/2002<br>cwells : 10/7/2002<br>carol : 9/27/2002<br>ckniffin : 9/27/2002<br>carol : 8/27/2002<br>carol : 8/26/2002<br>ckniffin : 8/23/2002<br>carol : 3/19/2002<br>alopez : 1/30/2002<br>alopez : 12/7/2001<br>terry : 12/5/2001<br>carol : 8/24/2001<br>carol : 8/24/2001<br>carol : 8/24/2001
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