3315 lines
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Entry
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- *608205 - MITOCHONDRIAL TRANS-2-ENOYL-CoA REDUCTASE; MECR
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- OMIM
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<p>
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<span class="h4">*608205</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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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</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/608205">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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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel 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=ENSG00000116353;t=ENST00000263702" 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=51102" 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=608205" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</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=ENSG00000116353;t=ENST00000263702" 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_001024732,NM_001349711,NM_001349712,NM_001349713,NM_001349714,NM_001349715,NM_001349716,NM_001349717,NM_016011,NR_146212,NR_146213,NR_146214,NR_146215,XM_011541539,XM_011541540,XM_011541541,XM_011541546,XM_047422042,XM_047422051,XM_047422055,XR_007060747,XR_007060748,XR_946663" 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_016011" 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=608205" 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=12192&isoform_id=12192_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/MECR" 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/4929595,12655133,48145523,119628058,119628059,119628060,119628061,193787781,194374831,334302832,767904535,767904538,767904541,767904551,1167503241,1167503281,1167503283,1167503289,1167503339,1167503351,1167503366,1167503368,1167803563,2217267936,2217267938,2217267940,2462509778,2462509780,2462509785,2462509787,2462509789,2462509791,2462509793" 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/Q9BV79" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=51102" 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=ENSG00000116353;t=ENST00000263702" 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=MECR" 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=MECR" 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+51102" 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/MECR" 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:51102" 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/51102" 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=chr1&hgg_gene=ENST00000263702.11&hgg_start=29167696&hgg_end=29230934&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:19691" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608205[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=608205[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/ENSG00000116353" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=MECR" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=MECR" 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=MECR" 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=MECR&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/PA142671471" 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:19691" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0033883.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1349441" 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/MECR#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:1349441" 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/51102/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://omia.org/OMIA002814/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=51102" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
|
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00012375;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00012375 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00012970;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00012970 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-050417-399" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:51102" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=MECR&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> 1236805005<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>
|
|
608205
|
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</span>
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</span>
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</div>
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</div>
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<div>
|
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
|
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MITOCHONDRIAL TRANS-2-ENOYL-CoA REDUCTASE; MECR
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
TRANS-2-ENOYL-CoA REDUCTASE, MITOCHONDRIAL<br />
|
|
2-ENOYL THIOESTER REDUCTASE<br />
|
|
NUCLEAR RECEPTOR-BINDING FACTOR 1; NRBF1
|
|
</span>
|
|
</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=MECR" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MECR</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/1/373?start=-3&limit=10&highlight=373">1p35.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:29167696-29230934&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'})">1:29,167,696-29,230,934</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=617282,620629" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/373?start=-3&limit=10&highlight=373">
|
|
1p35.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617282"> 617282 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
|
</td>
|
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|
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</tr>
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Optic atrophy 16
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620629"> 620629 </a>
|
|
|
|
</span>
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<p>The MECR gene encodes the last step of mitochondrial fatty acid synthesis. It is involved in the synthesis of lipoic acid and is required for mitochondrial respiratory competence (summary by <a href="#2" class="mim-tip-reference" title="Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others. <strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong> Am. J. Hum. Genet. 99: 1229-1244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27817865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27817865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27817865[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/10.1016/j.ajhg.2016.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27817865">Heimer et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27817865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By searching an EST database for sequences similar to S. cerevisiae trans-2-enoyl thioesterase, followed by PCR amplification, <a href="#4" class="mim-tip-reference" title="Miinalainen, I. J., Chen, Z.-J., Torkko, J. M., Pirila, P. L., Sormunen, R. T., Bergmann, U., Qin, Y.-M., Hiltunen, J. K. <strong>Characterization of 2-enoyl thioester reductase from mammals: an ortholog of Ybr026p/Mrf1'p of the yeast mitochondrial fatty acid synthesis type II.</strong> J. Biol. Chem. 278: 20154-20161, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12654921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12654921</a>] [<a href="https://doi.org/10.1074/jbc.M302851200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12654921">Miinalainen et al. (2003)</a> cloned NRBF1. The deduced 373-amino acid protein has a calculated molecular mass of 37 kD. Homologous proteins were identified in mammalian, nematode, and yeast databases. The mammalian proteins contain a putative N-terminal mitochondrial targeting signal, and all contain a tyrosine residue critical for catalysis in the yeast enzyme. Northern blot analysis detected a 1.4-kb NRBF1 transcript expressed at highest levels in skeletal and heart muscle. Expression was weaker in brain, placenta, liver, kidney, and pancreas, and no expression was detected in lung. SDS-PAGE showed that purified recombinant NRBF1 had an apparent molecular mass of about 37 kD. Size exclusion chromatography estimated a native mass of 65 kD, indicating that NRBF1 forms homodimers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12654921" 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="#4" class="mim-tip-reference" title="Miinalainen, I. J., Chen, Z.-J., Torkko, J. M., Pirila, P. L., Sormunen, R. T., Bergmann, U., Qin, Y.-M., Hiltunen, J. K. <strong>Characterization of 2-enoyl thioester reductase from mammals: an ortholog of Ybr026p/Mrf1'p of the yeast mitochondrial fatty acid synthesis type II.</strong> J. Biol. Chem. 278: 20154-20161, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12654921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12654921</a>] [<a href="https://doi.org/10.1074/jbc.M302851200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12654921">Miinalainen et al. (2003)</a> demonstrated that recombinant NRBF1 reduced trans-2-enoyl-CoA to acyl-CoA with chain lengths from C6 to C16 in an NADPH-dependent manner, with preference for medium chain-length substrates. Furthermore, expression of human NRBF1 in a yeast strain deficient in 2-enoyl thioester reductase restored mitochondrial respiratory function and allowed growth on glycerol. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12654921" 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="#4" class="mim-tip-reference" title="Miinalainen, I. J., Chen, Z.-J., Torkko, J. M., Pirila, P. L., Sormunen, R. T., Bergmann, U., Qin, Y.-M., Hiltunen, J. K. <strong>Characterization of 2-enoyl thioester reductase from mammals: an ortholog of Ybr026p/Mrf1'p of the yeast mitochondrial fatty acid synthesis type II.</strong> J. Biol. Chem. 278: 20154-20161, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12654921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12654921</a>] [<a href="https://doi.org/10.1074/jbc.M302851200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12654921">Miinalainen et al. (2003)</a> determined that the NRBF1 gene contains 10 exons and spans more than 37 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12654921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#4" class="mim-tip-reference" title="Miinalainen, I. J., Chen, Z.-J., Torkko, J. M., Pirila, P. L., Sormunen, R. T., Bergmann, U., Qin, Y.-M., Hiltunen, J. K. <strong>Characterization of 2-enoyl thioester reductase from mammals: an ortholog of Ybr026p/Mrf1'p of the yeast mitochondrial fatty acid synthesis type II.</strong> J. Biol. Chem. 278: 20154-20161, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12654921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12654921</a>] [<a href="https://doi.org/10.1074/jbc.M302851200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12654921">Miinalainen et al. (2003)</a> mapped the NRBF1 gene to chromosome 1p22.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12654921" 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>Dystonia, Childhood-Onset, with Optic Atrophy and Basal Ganglia Abnormalities</em></strong></p><p>
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In 7 patients from 5 unrelated families with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; <a href="/entry/617282">617282</a>), <a href="#2" class="mim-tip-reference" title="Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others. <strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong> Am. J. Hum. Genet. 99: 1229-1244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27817865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27817865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27817865[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/10.1016/j.ajhg.2016.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27817865">Heimer et al. (2016)</a> identified biallelic mutations in the MECR gene (<a href="#0001">608205.0001</a>-<a href="#0006">608205.0006</a>). The mutations, which were found by either whole-exome sequencing or direct sequencing of the MECR gene, were confirmed by Sanger sequencing and segregated with the disorder in the families. Patient fibroblasts from 4 families showed strongly reduced levels of MECR protein and about a 50% decrease in protein lipoylation compared to controls. Some patient cells also showed mild and variable decreases in mitochondrial respiratory chain and electron transport system activities. Patient cells did not show changes in mitochondrial morphology compared to controls. Two of the variants failed to fully rescue a growth defect in yeast complementation assays, consistent with a loss-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27817865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 12-year-old boy with childhood-onset dystonia and basal ganglia abnormalities but without optic atrophy, who was born to consanguineous Chinese parents (family G), <a href="#3" class="mim-tip-reference" title="Liu, Z., Shimura, M., Zhang, L., Zhang, W., Wang, J., Ogawa-Tominaga, M., Wang, J., Wang, X., Lv, J., Shi, W., Zhang, V. W., Murayama, K., Fang, F. <strong>Whole exome sequencing identifies a novel homozygous MECR mutation in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy.</strong> Mitochondrion 57: 222-229, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33401012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33401012</a>] [<a href="https://doi.org/10.1016/j.mito.2020.12.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33401012">Liu et al. (2021)</a> identified a homozygous mutation in the MECR gene (D304Y; <a href="#0007">608205.0007</a>). The authors noted that the patient was treated with lipoic acid since age 10, which may explain the absence of optic atrophy. The mutation, which was identified by whole-exome sequencing, was present in heterozygous state in the parents and an unaffected sib. MECR protein expression was reduced in patient fibroblasts. Molecular modeling suggested that the D304Y mutation resulted in disturbed protein stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33401012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Optic Atrophy 16</em></strong></p><p>
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In 2 sibs with optic atrophy-16 (OPA16; <a href="/entry/620629">620629</a>), <a href="#1" class="mim-tip-reference" title="Fiorini, C., Degiorgi, A., Cascavilla, M. L., Tropeano, C. V., La Morgia, C., Battista, M., Ormanbekova, D., Palombo, F., Carbonelli, M., Bandello, F., Carelli, V., Maresca, A., Barboni, P., Baruffini, E., Caporali, L. <strong>Recessive MECR pathogenic variants cause an LHON-like optic neuropathy.</strong> J. Med. Genet. 61: 93-101, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37734847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37734847</a>] [<a href="https://doi.org/10.1136/jmg-2023-109340" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="37734847">Fiorini et al. (2023)</a> identified homozygosity for the R258W mutation (<a href="#0005">608205.0005</a>) in the MECR gene. MECR protein expression was reduced in fibroblasts from the patients. Wildtype MECR and MECR with the R258W mutation were expressed in a yeast knockout for the etr1 gene (the ortholog of MECR) and protein expression of MECR with the R258W mutation was reduced compared to wildtype MECR. In the etr1 yeast mutants, abnormal oxygen consumption and lipoylation of Lat1 and Kgd2 were normalized by expression of wildtype MECR but not MECR with the R258W mutation. Supplementation with lipoic acid in the yeast mutants improved Lat1 and Kgd2 lipoylation and growth after treatment with hydrogen peroxide in the yeast expressing MECR with the R258W mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37734847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0001 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs762913101 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs762913101;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/rs762913101?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=rs762913101" 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=rs762913101" 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=RCV000415570 OR RCV000519749 OR RCV000755156 OR RCV003314592 OR RCV004758009" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415570, RCV000519749, RCV000755156, RCV003314592, RCV004758009" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415570...</a>
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<p>In a 48-year-old man of Ashkenazi Jewish descent (family A) with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; <a href="/entry/617282">617282</a>), <a href="#2" class="mim-tip-reference" title="Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others. <strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong> Am. J. Hum. Genet. 99: 1229-1244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27817865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27817865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27817865[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/10.1016/j.ajhg.2016.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27817865">Heimer et al. (2016)</a> identified compound heterozygous mutations in the MECR gene: a c.695G-A transition (c.695G-A, NM_016011.3), resulting in a gly232-to-glu (G232E) substitution at a conserved residue in the cofactor-binding domain, and a c.855T-G transversion, resulting in a tyr285-to-ter (Y285X; <a href="#0002">608205.0002</a>) substitution. An unrelated 2-year-old boy of mixed Jewish descent (family B) with the disorder was compound heterozygous for the G232E mutation and a 1-bp insertion (c.830+2_830+3insT; <a href="#0003">608205.0003</a>) in intron 7, resulting in a splice site defect and aberrant transcript production. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the 2 families. The c.695G-A mutation was not found in 256 alleles in the Ashkenazi Genome Project or in 206 in-house Ashkenazi Jewish controls, but was found at low frequency in the ExAC database (5 in 121,408). The c.855T-G mutation was not found in any of these 3 databases. The splice site mutation was found in 1 of 256 alleles in the Ashkenazi Genome Project database, in 0 of 210 alleles in the in-house database, and in 10 of 120,664 alleles in the ExAC database. Direct sequencing of these known variants in 2 affected adult brothers of Ashkenazi Jewish descent (family C) identified compound heterozygosity for the same 2 variants found in the 2-year-old boy from family B. In vitro studies showed that the G232E mutation was unable to fully rescue the respiratory defect in a yeast complementation model, consistent with an allele with diminished function; similar yeast complementation studies with the Y285X mutation showed that it resulted in a complete loss of function. Yeast strains transformed with these mutations showed absence of protein lipoylation. Western blot analysis showed no MECR signal with the G232E allele, suggesting that the mutant protein may not be stable, whereas there was evidence that the Y285X allele produced a truncated protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27817865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</strong>
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MECR, TYR285TER
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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> rs1057519286 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057519286;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/rs1057519286?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=rs1057519286" 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=rs1057519286" 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=RCV000415602 OR RCV000755157 OR RCV002266962" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415602, RCV000755157, RCV002266962" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415602...</a>
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<p>For discussion of the c.855T-G transversion (c.855T-G, NM_016011.3) in the MECR gene, resulting in a tyr285-to-ter (Y285X) substitution, that was found in compound heterozygous state in a patient with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; <a href="/entry/617282">617282</a>) by <a href="#2" class="mim-tip-reference" title="Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others. <strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong> Am. J. Hum. Genet. 99: 1229-1244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27817865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27817865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27817865[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/10.1016/j.ajhg.2016.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27817865">Heimer et al. (2016)</a>, see <a href="#0001">608205.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27817865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0003" class="mim-anchor"></a>
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<strong>.0003 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</strong>
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MECR, 1-BP INS, 830+2T
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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> rs756421370 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs756421370;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/rs756421370?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=rs756421370" 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=rs756421370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000521566 OR RCV000626033 OR RCV000755158 OR RCV003314605 OR RCV005027604" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000521566, RCV000626033, RCV000755158, RCV003314605, RCV005027604" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000521566...</a>
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<p>For discussion of the a 1-bp insertion in the MECR gene (c.830+2_830+3insT, NM_016011.3) that was found in compound heterozygous state in 3 patients from 2 unrelated families with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; <a href="/entry/617282">617282</a>) by <a href="#2" class="mim-tip-reference" title="Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others. <strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong> Am. J. Hum. Genet. 99: 1229-1244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27817865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27817865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27817865[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/10.1016/j.ajhg.2016.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27817865">Heimer et al. (2016)</a>, see <a href="#0001">608205.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27817865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</strong>
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MECR, TYR285CYS
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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> rs759218713 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs759218713;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/rs759218713?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=rs759218713" 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=rs759218713" 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=RCV000415576 OR RCV000755159" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415576, RCV000755159" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415576...</a>
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<p>In a 7-year-old girl of Tunisian origin (family D) with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; <a href="/entry/617282">617282</a>), <a href="#2" class="mim-tip-reference" title="Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others. <strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong> Am. J. Hum. Genet. 99: 1229-1244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27817865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27817865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27817865[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/10.1016/j.ajhg.2016.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27817865">Heimer et al. (2016)</a> identified a homozygous c.854A-G transition (c.854A-G, NM_016011.3) in the MECR gene, resulting in a tyr285-to-cys (Y285C) substitution at a conserved residue in the cofactor-binding domain. The mutation was found by Sanger sequencing and segregated with the disorder. The c.854A-G mutation was found in 1 of 120,182 alleles in the ExAC database and was not found in 256 alleles in the Ashkenazi Genome Project database. The residue affected was the same as a nonsense mutation identified in another patient with the disorder (Y285X; <a href="#0002">608205.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27817865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<strong>.0005 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</strong>
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OPTIC ATROPHY 16, INCLUDED (1 family)
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MECR, ARG258TRP
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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> rs145192716 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs145192716;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/rs145192716?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=rs145192716" 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=rs145192716" 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=RCV000415607 OR RCV000755160 OR RCV001865308 OR RCV003448300" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415607, RCV000755160, RCV001865308, RCV003448300" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415607...</a>
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<p><strong><em>Dystonia, Childhood-Onset, with Optic Atrophy and Basal Ganglia Abnormalities</em></strong></p><p>
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In 2 brothers of Anglo-Saxon descent (family E) with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; <a href="/entry/617282">617282</a>), <a href="#2" class="mim-tip-reference" title="Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others. <strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong> Am. J. Hum. Genet. 99: 1229-1244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27817865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27817865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27817865[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/10.1016/j.ajhg.2016.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27817865">Heimer et al. (2016)</a> identified compound heterozygous mutations in the MECR gene: a c.772C-T transition (c.772-C-T, NM_016011.3), resulting in an arg258-to-trp (R258W) substitution at a conserved residue in the cofactor-binding domain, and a 4-bp deletion (c.247_250del; <a href="#0006">608205.0006</a>), resulting in a frameshift and premature termination (Asn83HisfsTer4). The mutations, which were found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The c.772C-T mutation was found in 10 of 121,102 alleles in the ExAC database and was not found in 256 alleles in the Ashkenazi Genome Project database; the 4-bp deletion was not found in either database. Patient fibroblasts showed strongly reduced levels of MECR protein and about a 50% decrease in protein lipoylation compared to controls. However, patient cells showed only a modest decrease in activities of complexes I and IV (65-75% of control values). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27817865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Optic Atrophy 16</em></strong></p><p>
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In 2 sibs with optic atrophy-16 (OPA16; <a href="/entry/620629">620629</a>), <a href="#1" class="mim-tip-reference" title="Fiorini, C., Degiorgi, A., Cascavilla, M. L., Tropeano, C. V., La Morgia, C., Battista, M., Ormanbekova, D., Palombo, F., Carbonelli, M., Bandello, F., Carelli, V., Maresca, A., Barboni, P., Baruffini, E., Caporali, L. <strong>Recessive MECR pathogenic variants cause an LHON-like optic neuropathy.</strong> J. Med. Genet. 61: 93-101, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37734847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37734847</a>] [<a href="https://doi.org/10.1136/jmg-2023-109340" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="37734847">Fiorini et al. (2023)</a> identified homozygosity for the R258W mutation in the MECR gene. The mutation was identified by whole-exome sequencing and segregated with disease in the family. The mutation was reported in the gnomAD database (v2.1.1) with a minor allele frequency of 6.368e-5. MECR protein expression was reduced in fibroblasts from the patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37734847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</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">rs1057519287 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057519287;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=rs1057519287" 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=rs1057519287" 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=RCV000415548 OR RCV000755161 OR RCV003558371" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415548, RCV000755161, RCV003558371" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415548...</a>
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<p>For discussion of the 4-bp deletion (c.247_250del, NM_016011.3) in the MECR gene, resulting in a frameshift and premature termination (Asn83HisfsTer4), that was found in compound heterozygous state in 2 brothers with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; <a href="/entry/617282">617282</a>) by <a href="#2" class="mim-tip-reference" title="Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others. <strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong> Am. J. Hum. Genet. 99: 1229-1244, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27817865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27817865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27817865[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/10.1016/j.ajhg.2016.09.021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27817865">Heimer et al. (2016)</a>, see <a href="#0005">608205.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27817865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs761771473 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs761771473;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/rs761771473?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=rs761771473" 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=rs761771473" 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=RCV001527409" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001527409" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001527409</a>
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<p>In a 12-year-old boy, born of consanguineous Chinese parents (family G), with childhood-onset dystonia and basal ganglia abnormalities but without optic atrophy (DYTOABG; <a href="/entry/617282">617282</a>), <a href="#3" class="mim-tip-reference" title="Liu, Z., Shimura, M., Zhang, L., Zhang, W., Wang, J., Ogawa-Tominaga, M., Wang, J., Wang, X., Lv, J., Shi, W., Zhang, V. W., Murayama, K., Fang, F. <strong>Whole exome sequencing identifies a novel homozygous MECR mutation in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy.</strong> Mitochondrion 57: 222-229, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33401012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33401012</a>] [<a href="https://doi.org/10.1016/j.mito.2020.12.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33401012">Liu et al. (2021)</a> identified a homozygous c.910G-T transversion (c.910G-T, NM_016011.4) in the MECR gene, resulting in an asp304-to-tyr (D304Y) substitution at a conserved residue in the cofactor binding domain. The mutation was identified by whole-exome sequencing, and the patient's parents and unaffected sib were shown to be mutation carriers. The variant was not present in the 1000 Genomes Project, gnomAD, ExAC, and Exome Sequencing Project databases. MECR protein expression was reduced in patient fibroblasts. Molecular modeling suggested that the D304Y mutation resulted in disturbed protein stability. The authors noted that the patient was treated with lipoic acid from age 10 years, which may explain the absence of optic atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33401012" 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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Fiorini, C., Degiorgi, A., Cascavilla, M. L., Tropeano, C. V., La Morgia, C., Battista, M., Ormanbekova, D., Palombo, F., Carbonelli, M., Bandello, F., Carelli, V., Maresca, A., Barboni, P., Baruffini, E., Caporali, L.
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<strong>Recessive MECR pathogenic variants cause an LHON-like optic neuropathy.</strong>
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J. Med. Genet. 61: 93-101, 2023.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37734847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37734847</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37734847" 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-2023-109340" target="_blank">Full Text</a>]
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Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others.
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<strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong>
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Am. J. Hum. Genet. 99: 1229-1244, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27817865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27817865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27817865[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27817865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2016.09.021" target="_blank">Full Text</a>]
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Liu, Z., Shimura, M., Zhang, L., Zhang, W., Wang, J., Ogawa-Tominaga, M., Wang, J., Wang, X., Lv, J., Shi, W., Zhang, V. W., Murayama, K., Fang, F.
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<strong>Whole exome sequencing identifies a novel homozygous MECR mutation in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy.</strong>
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Mitochondrion 57: 222-229, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33401012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33401012</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33401012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.mito.2020.12.014" target="_blank">Full Text</a>]
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Miinalainen, I. J., Chen, Z.-J., Torkko, J. M., Pirila, P. L., Sormunen, R. T., Bergmann, U., Qin, Y.-M., Hiltunen, J. K.
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<strong>Characterization of 2-enoyl thioester reductase from mammals: an ortholog of Ybr026p/Mrf1'p of the yeast mitochondrial fatty acid synthesis type II.</strong>
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J. Biol. Chem. 278: 20154-20161, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12654921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12654921</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12654921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Hilary J. Vernon - updated : 06/22/2021<br>Cassandra L. Kniffin - updated : 01/03/2017
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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 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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Patricia A. Hartz : 10/24/2003
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<a id="editHistory" class="mim-anchor"></a>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </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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alopez : 01/08/2024
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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 : 12/11/2023<br>carol : 06/23/2021<br>carol : 06/22/2021<br>carol : 01/07/2017<br>carol : 01/06/2017<br>ckniffin : 01/03/2017<br>mgross : 03/22/2007<br>mgross : 10/24/2003
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<h3>
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<span class="mim-font">
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<strong>*</strong> 608205
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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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MITOCHONDRIAL TRANS-2-ENOYL-CoA REDUCTASE; MECR
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</h3>
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</div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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TRANS-2-ENOYL-CoA REDUCTASE, MITOCHONDRIAL<br />
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2-ENOYL THIOESTER REDUCTASE<br />
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NUCLEAR RECEPTOR-BINDING FACTOR 1; NRBF1
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</span>
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</h4>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: MECR</em></strong>
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</span>
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</p>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1236805005;
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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: 1p35.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:29,167,696-29,230,934 </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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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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Location
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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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</thead>
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<tbody>
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<td rowspan="2">
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<span class="mim-font">
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1p35.3
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<span class="mim-font">
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Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities
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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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617282
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<td>
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<span class="mim-font">
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Optic atrophy 16
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<td>
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<span class="mim-font">
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620629
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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</table>
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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>The MECR gene encodes the last step of mitochondrial fatty acid synthesis. It is involved in the synthesis of lipoic acid and is required for mitochondrial respiratory competence (summary by Heimer et al., 2016). </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>By searching an EST database for sequences similar to S. cerevisiae trans-2-enoyl thioesterase, followed by PCR amplification, Miinalainen et al. (2003) cloned NRBF1. The deduced 373-amino acid protein has a calculated molecular mass of 37 kD. Homologous proteins were identified in mammalian, nematode, and yeast databases. The mammalian proteins contain a putative N-terminal mitochondrial targeting signal, and all contain a tyrosine residue critical for catalysis in the yeast enzyme. Northern blot analysis detected a 1.4-kb NRBF1 transcript expressed at highest levels in skeletal and heart muscle. Expression was weaker in brain, placenta, liver, kidney, and pancreas, and no expression was detected in lung. SDS-PAGE showed that purified recombinant NRBF1 had an apparent molecular mass of about 37 kD. Size exclusion chromatography estimated a native mass of 65 kD, indicating that NRBF1 forms homodimers. </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>Miinalainen et al. (2003) demonstrated that recombinant NRBF1 reduced trans-2-enoyl-CoA to acyl-CoA with chain lengths from C6 to C16 in an NADPH-dependent manner, with preference for medium chain-length substrates. Furthermore, expression of human NRBF1 in a yeast strain deficient in 2-enoyl thioester reductase restored mitochondrial respiratory function and allowed growth on glycerol. </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>Miinalainen et al. (2003) determined that the NRBF1 gene contains 10 exons and spans more than 37 kb. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Miinalainen et al. (2003) mapped the NRBF1 gene to chromosome 1p22.3. </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>Dystonia, Childhood-Onset, with Optic Atrophy and Basal Ganglia Abnormalities</em></strong></p><p>
|
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In 7 patients from 5 unrelated families with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; 617282), Heimer et al. (2016) identified biallelic mutations in the MECR gene (608205.0001-608205.0006). The mutations, which were found by either whole-exome sequencing or direct sequencing of the MECR gene, were confirmed by Sanger sequencing and segregated with the disorder in the families. Patient fibroblasts from 4 families showed strongly reduced levels of MECR protein and about a 50% decrease in protein lipoylation compared to controls. Some patient cells also showed mild and variable decreases in mitochondrial respiratory chain and electron transport system activities. Patient cells did not show changes in mitochondrial morphology compared to controls. Two of the variants failed to fully rescue a growth defect in yeast complementation assays, consistent with a loss-of-function effect. </p><p>In a 12-year-old boy with childhood-onset dystonia and basal ganglia abnormalities but without optic atrophy, who was born to consanguineous Chinese parents (family G), Liu et al. (2021) identified a homozygous mutation in the MECR gene (D304Y; 608205.0007). The authors noted that the patient was treated with lipoic acid since age 10, which may explain the absence of optic atrophy. The mutation, which was identified by whole-exome sequencing, was present in heterozygous state in the parents and an unaffected sib. MECR protein expression was reduced in patient fibroblasts. Molecular modeling suggested that the D304Y mutation resulted in disturbed protein stability. </p><p><strong><em>Optic Atrophy 16</em></strong></p><p>
|
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In 2 sibs with optic atrophy-16 (OPA16; 620629), Fiorini et al. (2023) identified homozygosity for the R258W mutation (608205.0005) in the MECR gene. MECR protein expression was reduced in fibroblasts from the patients. Wildtype MECR and MECR with the R258W mutation were expressed in a yeast knockout for the etr1 gene (the ortholog of MECR) and protein expression of MECR with the R258W mutation was reduced compared to wildtype MECR. In the etr1 yeast mutants, abnormal oxygen consumption and lipoylation of Lat1 and Kgd2 were normalized by expression of wildtype MECR but not MECR with the R258W mutation. Supplementation with lipoic acid in the yeast mutants improved Lat1 and Kgd2 lipoylation and growth after treatment with hydrogen peroxide in the yeast expressing MECR with the R258W mutation. </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>7 Selected Examples):</strong>
|
|
</span>
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</h4>
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<div>
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<p />
|
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0001 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</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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MECR, GLY232GLU
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<br />
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SNP: rs762913101,
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gnomAD: rs762913101,
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ClinVar: RCV000415570, RCV000519749, RCV000755156, RCV003314592, RCV004758009
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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 48-year-old man of Ashkenazi Jewish descent (family A) with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; 617282), Heimer et al. (2016) identified compound heterozygous mutations in the MECR gene: a c.695G-A transition (c.695G-A, NM_016011.3), resulting in a gly232-to-glu (G232E) substitution at a conserved residue in the cofactor-binding domain, and a c.855T-G transversion, resulting in a tyr285-to-ter (Y285X; 608205.0002) substitution. An unrelated 2-year-old boy of mixed Jewish descent (family B) with the disorder was compound heterozygous for the G232E mutation and a 1-bp insertion (c.830+2_830+3insT; 608205.0003) in intron 7, resulting in a splice site defect and aberrant transcript production. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the 2 families. The c.695G-A mutation was not found in 256 alleles in the Ashkenazi Genome Project or in 206 in-house Ashkenazi Jewish controls, but was found at low frequency in the ExAC database (5 in 121,408). The c.855T-G mutation was not found in any of these 3 databases. The splice site mutation was found in 1 of 256 alleles in the Ashkenazi Genome Project database, in 0 of 210 alleles in the in-house database, and in 10 of 120,664 alleles in the ExAC database. Direct sequencing of these known variants in 2 affected adult brothers of Ashkenazi Jewish descent (family C) identified compound heterozygosity for the same 2 variants found in the 2-year-old boy from family B. In vitro studies showed that the G232E mutation was unable to fully rescue the respiratory defect in a yeast complementation model, consistent with an allele with diminished function; similar yeast complementation studies with the Y285X mutation showed that it resulted in a complete loss of function. Yeast strains transformed with these mutations showed absence of protein lipoylation. Western blot analysis showed no MECR signal with the G232E allele, suggesting that the mutant protein may not be stable, whereas there was evidence that the Y285X allele produced a truncated protein. </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 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</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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MECR, TYR285TER
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<br />
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SNP: rs1057519286,
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gnomAD: rs1057519286,
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ClinVar: RCV000415602, RCV000755157, RCV002266962
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.855T-G transversion (c.855T-G, NM_016011.3) in the MECR gene, resulting in a tyr285-to-ter (Y285X) substitution, that was found in compound heterozygous state in a patient with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; 617282) by Heimer et al. (2016), see 608205.0001. </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 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</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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MECR, 1-BP INS, 830+2T
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<br />
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SNP: rs756421370,
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gnomAD: rs756421370,
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ClinVar: RCV000521566, RCV000626033, RCV000755158, RCV003314605, RCV005027604
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the a 1-bp insertion in the MECR gene (c.830+2_830+3insT, NM_016011.3) that was found in compound heterozygous state in 3 patients from 2 unrelated families with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; 617282) by Heimer et al. (2016), see 608205.0001. </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 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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MECR, TYR285CYS
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<br />
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SNP: rs759218713,
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gnomAD: rs759218713,
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ClinVar: RCV000415576, RCV000755159
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a 7-year-old girl of Tunisian origin (family D) with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; 617282), Heimer et al. (2016) identified a homozygous c.854A-G transition (c.854A-G, NM_016011.3) in the MECR gene, resulting in a tyr285-to-cys (Y285C) substitution at a conserved residue in the cofactor-binding domain. The mutation was found by Sanger sequencing and segregated with the disorder. The c.854A-G mutation was found in 1 of 120,182 alleles in the ExAC database and was not found in 256 alleles in the Ashkenazi Genome Project database. The residue affected was the same as a nonsense mutation identified in another patient with the disorder (Y285X; 608205.0002). </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>.0005 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</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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OPTIC ATROPHY 16, INCLUDED (1 family)
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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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MECR, ARG258TRP
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<br />
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SNP: rs145192716,
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gnomAD: rs145192716,
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ClinVar: RCV000415607, RCV000755160, RCV001865308, RCV003448300
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</span>
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<span class="mim-text-font">
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<p />
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<p><strong><em>Dystonia, Childhood-Onset, with Optic Atrophy and Basal Ganglia Abnormalities</em></strong></p><p>
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In 2 brothers of Anglo-Saxon descent (family E) with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; 617282), Heimer et al. (2016) identified compound heterozygous mutations in the MECR gene: a c.772C-T transition (c.772-C-T, NM_016011.3), resulting in an arg258-to-trp (R258W) substitution at a conserved residue in the cofactor-binding domain, and a 4-bp deletion (c.247_250del; 608205.0006), resulting in a frameshift and premature termination (Asn83HisfsTer4). The mutations, which were found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The c.772C-T mutation was found in 10 of 121,102 alleles in the ExAC database and was not found in 256 alleles in the Ashkenazi Genome Project database; the 4-bp deletion was not found in either database. Patient fibroblasts showed strongly reduced levels of MECR protein and about a 50% decrease in protein lipoylation compared to controls. However, patient cells showed only a modest decrease in activities of complexes I and IV (65-75% of control values). </p><p><strong><em>Optic Atrophy 16</em></strong></p><p>
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In 2 sibs with optic atrophy-16 (OPA16; 620629), Fiorini et al. (2023) identified homozygosity for the R258W mutation in the MECR gene. The mutation was identified by whole-exome sequencing and segregated with disease in the family. The mutation was reported in the gnomAD database (v2.1.1) with a minor allele frequency of 6.368e-5. MECR protein expression was reduced in fibroblasts from the patients. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</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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MECR, 4-BP DEL, NT247
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<br />
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SNP: rs1057519287,
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ClinVar: RCV000415548, RCV000755161, RCV003558371
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the 4-bp deletion (c.247_250del, NM_016011.3) in the MECR gene, resulting in a frameshift and premature termination (Asn83HisfsTer4), that was found in compound heterozygous state in 2 brothers with childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (DYTOABG; 617282) by Heimer et al. (2016), see 608205.0005. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 DYSTONIA, CHILDHOOD-ONSET, WITH OPTIC ATROPHY AND BASAL GANGLIA ABNORMALITIES</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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MECR, ASP304TYR
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<br />
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SNP: rs761771473,
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gnomAD: rs761771473,
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ClinVar: RCV001527409
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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 12-year-old boy, born of consanguineous Chinese parents (family G), with childhood-onset dystonia and basal ganglia abnormalities but without optic atrophy (DYTOABG; 617282), Liu et al. (2021) identified a homozygous c.910G-T transversion (c.910G-T, NM_016011.4) in the MECR gene, resulting in an asp304-to-tyr (D304Y) substitution at a conserved residue in the cofactor binding domain. The mutation was identified by whole-exome sequencing, and the patient's parents and unaffected sib were shown to be mutation carriers. The variant was not present in the 1000 Genomes Project, gnomAD, ExAC, and Exome Sequencing Project databases. MECR protein expression was reduced in patient fibroblasts. Molecular modeling suggested that the D304Y mutation resulted in disturbed protein stability. The authors noted that the patient was treated with lipoic acid from age 10 years, which may explain the absence of optic atrophy. </p>
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</span>
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</div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Fiorini, C., Degiorgi, A., Cascavilla, M. L., Tropeano, C. V., La Morgia, C., Battista, M., Ormanbekova, D., Palombo, F., Carbonelli, M., Bandello, F., Carelli, V., Maresca, A., Barboni, P., Baruffini, E., Caporali, L.
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<strong>Recessive MECR pathogenic variants cause an LHON-like optic neuropathy.</strong>
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J. Med. Genet. 61: 93-101, 2023.
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[PubMed: 37734847]
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[Full Text: https://doi.org/10.1136/jmg-2023-109340]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Heimer, G., Keratar, J. M., Riley, L. G., Balasubramaniam, S., Eyal, E., Pietikainen, L. P., Hiltunen, J. K., Marek-Yagel, D., Hamada, J., Gregory, A., Rogers, C., Hogarth, P., and 24 others.
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<strong>MECR mutations cause childhood-onset dystonia and optic atrophy, a mitochondrial fatty acid synthesis disorder.</strong>
|
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Am. J. Hum. Genet. 99: 1229-1244, 2016.
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[PubMed: 27817865]
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[Full Text: https://doi.org/10.1016/j.ajhg.2016.09.021]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Liu, Z., Shimura, M., Zhang, L., Zhang, W., Wang, J., Ogawa-Tominaga, M., Wang, J., Wang, X., Lv, J., Shi, W., Zhang, V. W., Murayama, K., Fang, F.
|
|
<strong>Whole exome sequencing identifies a novel homozygous MECR mutation in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy.</strong>
|
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Mitochondrion 57: 222-229, 2021.
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[PubMed: 33401012]
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[Full Text: https://doi.org/10.1016/j.mito.2020.12.014]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Miinalainen, I. J., Chen, Z.-J., Torkko, J. M., Pirila, P. L., Sormunen, R. T., Bergmann, U., Qin, Y.-M., Hiltunen, J. K.
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<strong>Characterization of 2-enoyl thioester reductase from mammals: an ortholog of Ybr026p/Mrf1'p of the yeast mitochondrial fatty acid synthesis type II.</strong>
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J. Biol. Chem. 278: 20154-20161, 2003.
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[PubMed: 12654921]
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[Full Text: https://doi.org/10.1074/jbc.M302851200]
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</p>
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</ol>
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<div>
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<br />
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Contributors:
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Hilary J. Vernon - updated : 12/11/2023<br>Hilary J. Vernon - updated : 06/22/2021<br>Cassandra L. Kniffin - updated : 01/03/2017
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</span>
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Patricia A. Hartz : 10/24/2003
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alopez : 01/08/2024<br>carol : 12/11/2023<br>carol : 06/23/2021<br>carol : 06/22/2021<br>carol : 01/07/2017<br>carol : 01/06/2017<br>ckniffin : 01/03/2017<br>mgross : 03/22/2007<br>mgross : 10/24/2003
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