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Entry
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- *609575 - ACYL-CoA DEHYDROGENASE, VERY LONG-CHAIN; ACADVL
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*609575</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneFunction">Gene Function</a>
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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="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/609575">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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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div 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="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=ENSG00000072778;t=ENST00000356839" 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=37" 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=609575" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000072778;t=ENST00000356839" 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_000018,NM_001033859,NM_001270447,NM_001270448,XM_006721516,XM_011523829,XM_011523830,XM_047435931,XM_047435932,XR_007065296" 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_000018" 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=609575" 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 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=01940&isoform_id=01940_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/ACADVL" 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/790447,1008852,1235728,1703068,3273228,4557235,12653261,15277725,18044943,62896595,76496475,119610652,119610653,119610654,119610655,119610656,193786335,193787010,194374263,194380250,394025723,394025725,675359955,767992069,767992071,767992073,2217311600,2217311603,2462554979,2462554981,2462554983,2462554985,2462554988" 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/P49748" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=37" 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=ENSG00000072778;t=ENST00000356839" 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=ACADVL" 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=ACADVL" 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+37" 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/ACADVL" 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:37" 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/37" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr17&hgg_gene=ENST00000356839.10&hgg_start=7217125&hgg_end=7225266&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:92" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:92" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/acadvl" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=609575[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=609575[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/ACADVL/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000072778" 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=ACADVL" 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=ACADVL" 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=ACADVL" 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://research.cchmc.org/LOVD2/home.php?select_db=ACADVL" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ACADVL&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/PA24428" 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:92" 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/FBgn0034432.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:895149" 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/ACADVL#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:895149" 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/37/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/OMIA002140/" 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=37" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00017125;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-899" 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:37" 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=ACADVL&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> 237997005<br />
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<strong>ICD10CM:</strong> E71.310<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>
|
|
609575
|
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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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ACYL-CoA DEHYDROGENASE, VERY LONG-CHAIN; ACADVL
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
VLCAD
|
|
</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ACADVL" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ACADVL</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>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/17/139?start=-3&limit=10&highlight=139">17p13.1</a>
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|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:7217125-7225266&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">17:7,217,125-7,225,266</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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</span>
|
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</p>
|
|
</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
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/139?start=-3&limit=10&highlight=139">
|
|
17p13.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
VLCAD deficiency
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/201475"> 201475 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
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|
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</tbody>
|
|
</table>
|
|
</div>
|
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</div>
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<div>
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<p>The ACADVL gene encodes very long-chain acyl-CoA dehydrogenase (VLCAD) (<a href="https://enzyme.expasy.org/EC/1.3.99.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.3.99.13</a>). VLCAD is unique among the acyl-CoA dehydrogenases in its size, structure, and intramitochondrial distribution (<a href="#3" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T. <strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong> J. Clin. Invest. 95: 2465-2473, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7769092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7769092</a>] [<a href="https://doi.org/10.1172/JCI117947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7769092">Aoyama et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7769092" 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="#10" class="mim-tip-reference" title="Izai, K., Uchida, Y., Orii, T., Yamamoto, S., Hashimoto, T. <strong>Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. I. Purification and properties of very-long-chain acyl-coenzyme A dehydrogenase.</strong> J. Biol. Chem. 267: 1027-1033, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1730632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1730632</a>]" pmid="1730632">Izai et al. (1992)</a> identified and purified a novel acyl-CoA dehydrogenase, Acadvl, from rat liver mitochondria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1730632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ueno, I., Kamijo, T., Yamaguchi, S., Rhead, W. J., Tanaka, K., Hashimoto, T. <strong>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</strong> Am. J. Hum. Genet. 57: 273-283, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668252</a>]" pmid="7668252">Aoyama et al. (1995)</a> cloned and sequenced 2 overlapping cDNA clones corresponding to human mitochondrial VLCAD. The cDNA encodes a 655-amino acid protein with a 40-amino acid leader peptide, yielding a mature 615-residue protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668252" 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>Whereas the other acyl-CoA dehydrogenases are homotetramers of a 43- to 45-kD subunit, VLCAD purified from human liver was shown by <a href="#3" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T. <strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong> J. Clin. Invest. 95: 2465-2473, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7769092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7769092</a>] [<a href="https://doi.org/10.1172/JCI117947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7769092">Aoyama et al. (1995)</a> to be a 154-kD homodimer of a 70-kD subunit. VLCAD was loosely bound to the mitochondrial inner membrane and required detergent for stabilization. In contrast, the other 3 acyl-CoA dehydrogenases others were readily extractable into the soluble fraction without detergent, indicating that they are located in the mitochondrial matrix. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7769092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Andresen, B. S., Bross, P., Vianey-Saban, C., Divry, P., Zabot, M.-T., Roe, C. R., Nada, M. A., Byskov, A., Kruse, T. A., Neve, S., Kristiansen, K., Knudsen, I., Corydon, M. J., Gregersen, N. <strong>Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene.</strong> Hum. Molec. Genet. 5: 461-472, 1996. Note: Erratum: Hum. Molec. Genet. 5: 1390 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845838</a>] [<a href="https://doi.org/10.1093/hmg/5.4.461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845838">Andresen et al. (1996)</a> isolated cDNA clones for human VLCAD by using rat Vlcad cDNA sequences to identify an EST from human fetal brain in the GenBank database, followed by 5-prime and 3-prime rapid amplification of cDNA ends (RACE) to identify overlapping clones. Sequence analysis of the coding region and the 5-prime noncoding region of the VLCAD cDNA showed no differences with the sequence published by <a href="#3" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T. <strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong> J. Clin. Invest. 95: 2465-2473, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7769092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7769092</a>] [<a href="https://doi.org/10.1172/JCI117947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7769092">Aoyama et al. (1995)</a>. <a href="#1" class="mim-tip-reference" title="Andresen, B. S., Bross, P., Vianey-Saban, C., Divry, P., Zabot, M.-T., Roe, C. R., Nada, M. A., Byskov, A., Kruse, T. A., Neve, S., Kristiansen, K., Knudsen, I., Corydon, M. J., Gregersen, N. <strong>Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene.</strong> Hum. Molec. Genet. 5: 461-472, 1996. Note: Erratum: Hum. Molec. Genet. 5: 1390 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845838</a>] [<a href="https://doi.org/10.1093/hmg/5.4.461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845838">Andresen et al. (1996)</a> found 26 to 33% homology between VLCAD and other human acyl-CoA dehydrogenases. Northern blot analysis detected a 2.4-kb mRNA transcript in a variety of human tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7769092+8845838" 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>By real-time RT-PCR, <a href="#19" class="mim-tip-reference" title="Zhou, C., Blumberg, B. <strong>Overlapping gene structure of human VLCAD and DLG4.</strong> Gene 305: 161-166, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12609736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12609736</a>] [<a href="https://doi.org/10.1016/s0378-1119(02)01235-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12609736">Zhou and Blumberg (2003)</a> detected VLCAD expression in all tissues examined, with highest expression in heart and skeletal muscle, followed by placenta and pancreas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12609736" 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="#10" class="mim-tip-reference" title="Izai, K., Uchida, Y., Orii, T., Yamamoto, S., Hashimoto, T. <strong>Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. I. Purification and properties of very-long-chain acyl-coenzyme A dehydrogenase.</strong> J. Biol. Chem. 267: 1027-1033, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1730632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1730632</a>]" pmid="1730632">Izai et al. (1992)</a> found that the properties of Acadvl purified from rat liver mitochondria differed from those of the short (ACADS; <a href="/entry/606885">606885</a>)-, medium (ACADM; <a href="/entry/607008">607008</a>)-, and long (ACADL; <a href="/entry/609576">609576</a>)-chain acyl-CoA dehydrogenases. Acadvl was active toward very long-chain fatty acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1730632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T. <strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong> J. Clin. Invest. 95: 2465-2473, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7769092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7769092</a>] [<a href="https://doi.org/10.1172/JCI117947" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7769092">Aoyama et al. (1995)</a> found that human VLCAD had 10 times higher specific activity toward palmitoyl-CoA than did LCAD. The enzyme was found to catalyze the major part of mitochondrial palmitoyl-CoA dehydrogenation in liver, heart, skeletal muscle, and skin fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7769092" 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="#16" class="mim-tip-reference" title="Strauss, A. W., Powell, C. K., Hale, D. E., Anderson, M. M., Ahuja, A., Brackett, J. C., Sims, H. F. <strong>Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.</strong> Proc. Nat. Acad. Sci. 92: 10496-10500, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479827</a>] [<a href="https://doi.org/10.1073/pnas.92.23.10496" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7479827">Strauss et al. (1995)</a> determined that the ACADVL gene contains 20 exons. The ACADVL gene is about 5.4 kb long (<a href="#19" class="mim-tip-reference" title="Zhou, C., Blumberg, B. <strong>Overlapping gene structure of human VLCAD and DLG4.</strong> Gene 305: 161-166, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12609736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12609736</a>] [<a href="https://doi.org/10.1016/s0378-1119(02)01235-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12609736">Zhou and Blumberg, 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12609736+7479827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Zhang, L.-F., Ding, J.-H., Yang, B.-Z., He, G.-C., Roe, C. <strong>Characterization of the bidirectional promoter region between the human genes encoding VLCAD and PSD-95.</strong> Genomics 82: 660-668, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14611808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14611808</a>] [<a href="https://doi.org/10.1016/s0888-7543(03)00211-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14611808">Zhang et al. (2003)</a> noted that the VLCAD and the DLG4 (<a href="/entry/602887">602887</a>) genes are located in a head-to-head orientation on chromosome 17p. The transcribed regions of the 2 genes overlap by about 220 bp. Using serial promoter partial deletion constructs in a reporter gene assay, they found that the essential promoter activity of DLG4 is carried within a region of about 400 bp and covers the entire VLCAD minimal promoter, which spans about 270 bp. The results from di-(2-ethylhexyl) phthalate (DEHP)-treated HepG2 cells revealed that the minimal VLCAD promoter can upregulate VLCAD expression in response to DEHP treatment. Site-directed mutagenesis experiments showed that a mutated AP2 (<a href="/entry/107580">107580</a>)-binding site markedly reduced the transcriptional activity of both the VLCAD and DLG4 promoters and abolished the minimal VLCAD promoter's response to DEHP treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14611808" 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>Independently, <a href="#19" class="mim-tip-reference" title="Zhou, C., Blumberg, B. <strong>Overlapping gene structure of human VLCAD and DLG4.</strong> Gene 305: 161-166, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12609736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12609736</a>] [<a href="https://doi.org/10.1016/s0378-1119(02)01235-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12609736">Zhou and Blumberg (2003)</a> determined that the VLCAD and DLG4 genes overlap. The 2 genes share 245 nucleotides at their 5-prime ends, and the transcription start site for DLG4 extends into the coding region of VLCAD exon 1. The upstream regions of the VLCAD and DLG4 genes, including the overlapping region, contain 2 potential TATA-less promoters with potential binding sites for several common transcription factors. RT-PCR detected unique patterns of expression for VLCAD and DLG4, indicating that, although they share common regulatory elements, VLCAD and DLG4 also have distinct tissue-specific elements. The mouse Dlg4 and Vlcad genes are oriented in a head-to-head manner, but they do not overlap and are separated by almost 3.5 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12609736" 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="#1" class="mim-tip-reference" title="Andresen, B. S., Bross, P., Vianey-Saban, C., Divry, P., Zabot, M.-T., Roe, C. R., Nada, M. A., Byskov, A., Kruse, T. A., Neve, S., Kristiansen, K., Knudsen, I., Corydon, M. J., Gregersen, N. <strong>Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene.</strong> Hum. Molec. Genet. 5: 461-472, 1996. Note: Erratum: Hum. Molec. Genet. 5: 1390 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845838</a>] [<a href="https://doi.org/10.1093/hmg/5.4.461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845838">Andresen et al. (1996)</a> mapped the ACADVL gene to human chromosome 17p13.1-p11.2 by analysis of rodent-human hybrids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845838" 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>By fluorescence in situ hybridization, <a href="#12" class="mim-tip-reference" title="Orii, K. O., Saito-Ohara, F., Ikeuchi, T., Orii, T., Kondo, N., Aoyama, T., Hashimoto, T. <strong>Assignment of the gene for very-long-chain acyl-CoA dehydrogenase (Acadvl) to mouse chromosome band 11B2-B5 by in situ hybridization.</strong> Cytogenet. Cell Genet. 78: 25-26, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9345900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9345900</a>] [<a href="https://doi.org/10.1159/000134619" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9345900">Orii et al. (1997)</a> mapped the murine Acadvl gene to chromosome 11 in a region of synteny to human 17p13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9345900" 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>In cultured fibroblasts of 2 patients with VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#2" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ueno, I., Kamijo, T., Yamaguchi, S., Rhead, W. J., Tanaka, K., Hashimoto, T. <strong>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</strong> Am. J. Hum. Genet. 57: 273-283, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668252</a>]" pmid="7668252">Aoyama et al. (1995)</a> identified a 105-bp deletion in the ACADVL gene (<a href="#0001">609575.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Andresen, B. S., Bross, P., Vianey-Saban, C., Divry, P., Zabot, M.-T., Roe, C. R., Nada, M. A., Byskov, A., Kruse, T. A., Neve, S., Kristiansen, K., Knudsen, I., Corydon, M. J., Gregersen, N. <strong>Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene.</strong> Hum. Molec. Genet. 5: 461-472, 1996. Note: Erratum: Hum. Molec. Genet. 5: 1390 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845838</a>] [<a href="https://doi.org/10.1093/hmg/5.4.461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845838">Andresen et al. (1996)</a> identified 9 different mutations in the ACADVL gene in 4 unrelated patients with VLCAD deficiency. Two patients carried 3 different mutations. Different mutations were observed in each of the patients. Western blot analysis on fibroblasts from 3 of the patients revealed severe quantitative reduction in VLCAD protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Mathur, A., Sims, H. F., Gopalakrishnan, D., Gibson, B., Rinaldo, P., Vockley, J., Hug, G., Strauss, A. W. <strong>Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death.</strong> Circulation 99: 1337-1343, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10077518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10077518</a>] [<a href="https://doi.org/10.1161/01.cir.99.10.1337" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10077518">Mathur et al. (1999)</a> identified 21 different mutations in the ACADVL gene in 18 of 37 children with cardiomyopathy, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis. Sixty-seven percent of children had severe dilated or hypertrophic cardiomyopathy at presentation. In 7 patients, only 1 mutation was found despite direct sequencing of all exons. Missense, frameshift, and splice consensus sequence mutations were seen, as well as in-frame deletions. Eighty percent of these mutations were associated with cardiomyopathy. The authors concluded that infantile cardiomyopathy is the most common clinical phenotype for VLCAD deficiency and highlighted the marked allelic heterogeneity in this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10077518" 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>Since VLCAD-deficient patients frequently harbor missense mutations with unpredictable effects on enzyme activity, <a href="#9" class="mim-tip-reference" title="Gobin-Limballe, S., Djouadi, F., Aubey, F., Olpin, S., Andresen, B. S., Yamaguchi, S., Mandel, H., Fukao, T., Ruiter, J. P. N., Wanders, R. J. A., McAndrew, R., Kim, J. J., Bastin, J. <strong>Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy.</strong> Am. J. Hum. Genet. 81: 1133-1143, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17999356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17999356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17999356[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/10.1086/522375" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17999356">Gobin-Limballe et al. (2007)</a> investigated the response to bezafibrate as a function of genotype in 33 VLCAD-deficient fibroblast cell lines representing 45 different mutations. Treatment with bezafibrate (400 microM for 48 hours) resulted in a marked increase in FAO capacities, often leading to restoration of normal values, for 21 genotypes that mainly corresponded to patients with the myopathic phenotype. In contrast, bezafibrate induced no changes in FAO for 11 genotypes corresponding to severe neonatal or infantile phenotypes. This pattern of response was not due to differential inductions of VLCAD mRNA, as shown by quantitative real-time PCR, but reflected variable increases in measured VLCAD residual enzyme activity in response to bezafibrate. Genotype cross-analysis allowed the identification of alleles carrying missense mutations, which could account for these different pharmacologic profiles and, on this basis, led to the characterization of 9 mild and 11 severe missense mutations. The responses to bezafibrate reflected the severity of the metabolic blockage in various genotypes, which appeared to be correlated with the phenotype. This study emphasized the potential of bezafibrate, a widely prescribed hypolipidemic drug, for the correction of VLCAD deficiency and exemplified the integration of molecular information in a therapeutic strategy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17999356" 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>Of the 52 patients with VLCAD deficiency reported by <a href="#13" class="mim-tip-reference" title="Pena, L. D. M., van Calcar, S. C., Hansen, J., Edick, M. J., Vockley, C. W., Leslie, N., Cameron, C., Mohsen, A.-W., Berry, S. A., Arnold, G. L., Vockley, J. <strong>Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.</strong> Molec. Genet. Metab. 118: 272-281, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27209629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27209629</a>] [<a href="https://doi.org/10.1016/j.ymgme.2016.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27209629">Pena et al. (2016)</a>, molecular testing was available for 46. Two mutations were identified in 44 of these while only 1 mutation was identified in the remaining 2. Most (38 of 46, 83%) were compound heterozygous, and of the 50 different alleles reported, 26 were novel. <a href="#6" class="mim-tip-reference" title="Evans, M., Andresen, B. S., Nation, J., Boneh, A. <strong>VLCAD deficiency: follow-up and outcome of patients diagnosed through newborn screening in Victoria.</strong> Molec. Genet. Metab. 118: 282-287, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27246109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27246109</a>] [<a href="https://doi.org/10.1016/j.ymgme.2016.05.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27246109">Evans et al. (2016)</a> reported 5 novel mutations among 22 patients with VLCAD deficiency identified in Victoria, Australia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27209629+27246109" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Cox, K. B., Hamm, D. A., Millington, D. S., Matern, D., Vockley, J., Rinaldo, P., Pinkert, C. A., Rhead, W. J., Lindsey, J. R., Wood, P. A. <strong>Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse.</strong> Hum. Molec. Genet. 10: 2069-2077, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11590124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11590124</a>] [<a href="https://doi.org/10.1093/hmg/10.19.2069" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11590124">Cox et al. (2001)</a> generated mice with VLCAD deficiency (Vlcad -/-) and compared their pathologic and biochemical phenotypes to mice with Lcad deficiency (Lcad -/-) and wildtype mice. Vlcad -/- mice had milder fatty acid change in liver and heart. Dehydrogenation of various acyl-CoA substrates by liver, heart, and skeletal muscle mitochondria differed among the 3 genotypes. The results for liver were most informative as Vlcad -/- mice had a reduction in activity toward palmitoyl-CoA and oleoyl-CoA (58% and 64% of wildtype, respectively), whereas Lcad -/- mice showed a more profoundly reduced activity toward these substrates (35% and 32% of wildtype, respectively), with a significant reduction of activity toward the branched chain substrate 2,6-dimethylheptanoyl-CoA. C16 and C18 acylcarnitines were elevated in bile, blood, and serum of fasted Vlcad -/- mice, whereas abnormally elevated C12 and C14 acylcarnitines were prominent in Lcad -/- mice. Progeny with the combined Lcad +/+//Vlcad +/- genotype were overrepresented in offspring from sires and dams heterozygous for both Lcad and Vlcad mutations. In contrast, no live mice with a compound Lcad -/-/Vlcad -/- genotype were detected, suggesting that this genotype may be lethal in utero or in the periparturient period. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11590124" 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>To define the onset and molecular mechanism of myocardial disease, <a href="#7" class="mim-tip-reference" title="Exil, V. J., Roberts, R. L., Sims, H., McLaughlin, J. E., Malkin, R. A., Gardner, C. D., Ni, G., Rottman, J. N., Strauss, A. W. <strong>Very-long-chain acyl-coenzyme A dehydrogenase deficiency in mice.</strong> Circ. Res. 93: 448-455, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12893739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12893739</a>] [<a href="https://doi.org/10.1161/01.RES.0000088786.19197.E4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12893739">Exil et al. (2003)</a> generated Vlcad-deficient mice by homologous recombination. They found that Vlcad-deficient hearts had microvesicular lipid accumulation and marked mitochondrial proliferation, and demonstrated facilitated induction of polymorphic ventricular tachycardia, without antecedent stress. The expression of acyl-CoA synthetase-1 (ACS1; <a href="/entry/152425">152425</a>), adipophilin, Ap2, cytochrome c, and the peroxisome proliferator-activated receptor-gamma coactivator-1 (PPARGC1; <a href="/entry/604517">604517</a>) were increased immediately after birth, preceding overt histologic lipidosis, whereas Acs1 expression was markedly downregulated in the adult heart. <a href="#7" class="mim-tip-reference" title="Exil, V. J., Roberts, R. L., Sims, H., McLaughlin, J. E., Malkin, R. A., Gardner, C. D., Ni, G., Rottman, J. N., Strauss, A. W. <strong>Very-long-chain acyl-coenzyme A dehydrogenase deficiency in mice.</strong> Circ. Res. 93: 448-455, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12893739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12893739</a>] [<a href="https://doi.org/10.1161/01.RES.0000088786.19197.E4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12893739">Exil et al. (2003)</a> concluded that mice with Vlcad deficiency have altered expression of a variety of genes in the fatty acid metabolic pathway from birth, reflecting metabolic feedback circuits, with progression to ultrastructural and physiologic correlates of the associated human disease in the absence of stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12893739" 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>In 2 patients with VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#2" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ueno, I., Kamijo, T., Yamaguchi, S., Rhead, W. J., Tanaka, K., Hashimoto, T. <strong>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</strong> Am. J. Hum. Genet. 57: 273-283, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668252</a>]" pmid="7668252">Aoyama et al. (1995)</a> identified a 105-bp deletion encompassing bases 1078-1182 in the VLCAD cDNA. The deletion was thought to result from exon skipping and was predicted to result in the in-frame deletion of 35 amino acids, beginning with val360 of the precursor VLCAD. Using the vaccinia viral system, <a href="#2" class="mim-tip-reference" title="Aoyama, T., Souri, M., Ueno, I., Kamijo, T., Yamaguchi, S., Rhead, W. J., Tanaka, K., Hashimoto, T. <strong>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</strong> Am. J. Hum. Genet. 57: 273-283, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668252</a>]" pmid="7668252">Aoyama et al. (1995)</a> performed quantitative cDNA expression of normal human VLCAD in the patients' fibroblasts and demonstrated that raising VLCAD activity to approximately 20% of normal control fibroblast activity raised palmitic acid beta-oxidation flux to the level found in control fibroblasts. The mutation described in these patients has consequences for enzyme folding and assembly that are similar to those for the well-characterized A985G mutation (lys329-to-glu; <a href="/entry/607008#0001">607008.0001</a>) found in approximately 90% of the mutant alleles in patients with MCAD deficiency (<a href="/entry/201450">201450</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs113690956 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113690956;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/rs113690956?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=rs113690956" 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=rs113690956" 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=RCV000001689 OR RCV000210824" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001689, RCV000210824" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001689...</a>
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<p>In a patient with VLCAD deficiency (<a href="/entry/201475">201475</a>) associated with infantile cardiomyopathy and sudden death, <a href="#16" class="mim-tip-reference" title="Strauss, A. W., Powell, C. K., Hale, D. E., Anderson, M. M., Ahuja, A., Brackett, J. C., Sims, H. F. <strong>Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.</strong> Proc. Nat. Acad. Sci. 92: 10496-10500, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479827</a>] [<a href="https://doi.org/10.1073/pnas.92.23.10496" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7479827">Strauss et al. (1995)</a> identified a homozygous G-to-A transition in the consensus dinucleotide of the donor splice site in intron 11 of the ACADVL gene, resulting in the skipping of exon 11. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7479827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 VLCAD DEFICIENCY</strong>
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ACADVL, ARG613TRP
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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> rs118204014 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204014;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/rs118204014?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=rs118204014" 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=rs118204014" 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=RCV000001690 OR RCV000185733" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001690, RCV000185733" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001690...</a>
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<p>In a patient with VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#15" class="mim-tip-reference" title="Souri, M., Aoyama, T., Orii, K., Yamaguchi, S., Hashimoto, T. <strong>Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients.</strong> Am. J. Hum. Genet. 58: 97-106, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554073</a>]" pmid="8554073">Souri et al. (1996)</a> identified compound heterozygosity for 2 mutations in the ACADVL gene: a 1837C-T transition, resulting in an arg613-to-trp (R613W) substitution, and a 135-bp deletion of nucleotides 343-477, resulting in the loss of 45 amino acids from the VLCAD protein (<a href="#0005">609575.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554073" 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 VLCAD DEFICIENCY</strong>
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ACADVL, IVS5AS, 1-BP DEL, G, -1
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001691 OR RCV000077915 OR RCV003128226" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001691, RCV000077915, RCV003128226" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001691...</a>
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<p>In a patient with VLCAD deficiency (<a href="/entry/201475">201475</a>) associated with infantile cardiomyopathy and sudden death, <a href="#16" class="mim-tip-reference" title="Strauss, A. W., Powell, C. K., Hale, D. E., Anderson, M. M., Ahuja, A., Brackett, J. C., Sims, H. F. <strong>Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.</strong> Proc. Nat. Acad. Sci. 92: 10496-10500, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479827</a>] [<a href="https://doi.org/10.1073/pnas.92.23.10496" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7479827">Strauss et al. (1995)</a> identified compound heterozygosity for 2 mutations in the ACADVL gene: R613W (<a href="#0003">609575.0003</a>) and a 1-bp deletion of one of the 2 guanine nucleotides forming the intron-exon 6 boundary. The normal sequence is ccccagGAA and the mutant sequence was cccaGAA. The authors noted that the most likely consequence of this deletion would be an alternation in splicing because of loss of the conserved ag dinucleotide at the splice acceptor site. Alternatively, splicing at this site might occur but this would result in loss of a single nucleotide in exon 6, causing a shift in the mRNA reading frame. In either event, this mutation would most likely result in an unstable mRNA and lack of VLCAD protein expression from the mutant allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7479827" 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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ACADVL, 135-BP DEL
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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> rs387906249 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906249;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/rs387906249?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=rs387906249" 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=rs387906249" 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=RCV000001691 OR RCV000077915 OR RCV003128226" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001691, RCV000077915, RCV003128226" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001691...</a>
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<p>For discussion of the 135-bp deletion of nucleotides 343-477 in the ACADVL gene, resulting in the loss of 45 amino acids, that was found in compound heterozygous state in a patient with VLCAD deficiency (<a href="/entry/201475">201475</a>) by <a href="#15" class="mim-tip-reference" title="Souri, M., Aoyama, T., Orii, K., Yamaguchi, S., Hashimoto, T. <strong>Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients.</strong> Am. J. Hum. Genet. 58: 97-106, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554073</a>]" pmid="8554073">Souri et al. (1996)</a>, see <a href="#0003">609575.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554073" 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 VLCAD DEFICIENCY</strong>
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ACADVL, 3-BP DEL, NT388
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906251 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906251;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=rs387906251" 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=rs387906251" 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=RCV000001693 OR RCV001596930 OR RCV003430629" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001693, RCV001596930, RCV003430629" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001693...</a>
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<p>In a patient with VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#15" class="mim-tip-reference" title="Souri, M., Aoyama, T., Orii, K., Yamaguchi, S., Hashimoto, T. <strong>Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients.</strong> Am. J. Hum. Genet. 58: 97-106, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554073</a>]" pmid="8554073">Souri et al. (1996)</a> identified a homozygous 3-bp deletion in the ACADVL gene (nucleotides 388-390), resulting in deletion of glu130 (E130X). In another patient, <a href="#15" class="mim-tip-reference" title="Souri, M., Aoyama, T., Orii, K., Yamaguchi, S., Hashimoto, T. <strong>Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients.</strong> Am. J. Hum. Genet. 58: 97-106, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554073</a>]" pmid="8554073">Souri et al. (1996)</a> found the 3-bp deletion mutation in compound heterozygosity with the K382Q mutation (<a href="#0008">609575.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554073" 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="0007" class="mim-anchor"></a>
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<strong>.0007 VLCAD DEFICIENCY</strong>
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ACADVL, 3-BP DEL, NT895
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906252 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906252;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=rs387906252" 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=rs387906252" 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=RCV000001694 OR RCV000077926" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001694, RCV000077926" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001694...</a>
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<p>In an infant with VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#15" class="mim-tip-reference" title="Souri, M., Aoyama, T., Orii, K., Yamaguchi, S., Hashimoto, T. <strong>Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients.</strong> Am. J. Hum. Genet. 58: 97-106, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554073</a>]" pmid="8554073">Souri et al. (1996)</a> found deletion of nucleotides 895-897 in the ACADVL gene, resulting in deletion of lys299 (K299X). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554073" 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="0008" class="mim-anchor"></a>
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<h4>
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<strong>.0008 VLCAD DEFICIENCY</strong>
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ACADVL, LYS382GLN
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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> rs118204015 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204015;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/rs118204015?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=rs118204015" 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=rs118204015" 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=RCV000001695" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001695" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001695</a>
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</span>
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<span class="mim-text-font">
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<p>In an infant with VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#15" class="mim-tip-reference" title="Souri, M., Aoyama, T., Orii, K., Yamaguchi, S., Hashimoto, T. <strong>Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients.</strong> Am. J. Hum. Genet. 58: 97-106, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8554073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8554073</a>]" pmid="8554073">Souri et al. (1996)</a> identified a 1144A-C transversion in the ACADVL gene, resulting in a lys382-to-gln (K382Q) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8554073" 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="0009" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0009 VLCAD DEFICIENCY</strong>
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</span>
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</h4>
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<div style="float: left;">
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ACADVL, GLY401ASP
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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> rs2309689 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2309689;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/rs2309689?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=rs2309689" 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=rs2309689" 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=RCV000020072 OR RCV000077903" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000020072, RCV000077903" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000020072...</a>
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<span class="mim-text-font">
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<p>In a 42-year-old woman with late-onset VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#14" class="mim-tip-reference" title="Smelt, A. H. M., Poorthuis, B. J. H. M., Onkenhout, W., Scholte, H. R., Andresen, B. S., van Duinen, S. G., Gregersen, N., Wintzen, A. R. <strong>Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset.</strong> Ann. Neurol. 43: 540-544, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9546340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9546340</a>] [<a href="https://doi.org/10.1002/ana.410430422" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9546340">Smelt et al. (1998)</a> identified compound heterozygosity for 2 mutations in the ACADVL gene: a G-to-A transition in exon 13, resulting in a gly401-to-asp (G401D) substitution, and a G-to-A transition in exon 14, resulting in an arg410-to-his (R410H; <a href="#0010">609575.0010</a>) substitution. The patient had recurrent rhabdomyolysis and markedly elevated levels of tetradecadienoic acid and hexadecadienoic acid. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9546340" 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="0010" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0010 VLCAD DEFICIENCY</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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ACADVL, ARG410HIS
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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> rs118204016 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204016;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/rs118204016?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=rs118204016" 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=rs118204016" 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=RCV000001701 OR RCV000724571 OR RCV001003625" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001701, RCV000724571, RCV001003625" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001701...</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the G-to-A transition in exon 14 of the ACADVL gene, resulting in an arg410-to-his (R410H), that was found in compound heterozygous state in a patient with VLCAD deficiency by <a href="#14" class="mim-tip-reference" title="Smelt, A. H. M., Poorthuis, B. J. H. M., Onkenhout, W., Scholte, H. R., Andresen, B. S., van Duinen, S. G., Gregersen, N., Wintzen, A. R. <strong>Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset.</strong> Ann. Neurol. 43: 540-544, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9546340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9546340</a>] [<a href="https://doi.org/10.1002/ana.410430422" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9546340">Smelt et al. (1998)</a>, see <a href="#0009">609575.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9546340" 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="0011" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0011 VLCAD DEFICIENCY</strong>
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</span>
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</h4>
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</div>
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<div style="float: left;">
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ACADVL, PRO65LEU AND LYS247GLN
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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> rs28934585 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28934585;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/rs28934585?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=rs28934585" 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=rs28934585" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906253 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906253;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=rs387906253" 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=rs387906253" 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=RCV000001698 OR RCV000020076 OR RCV000077913 OR RCV000420053 OR RCV001250508" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001698, RCV000020076, RCV000077913, RCV000420053, RCV001250508" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001698...</a>
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<p>In an Israeli patient with VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#17" class="mim-tip-reference" title="Watanabe, H., Orii, K. E., Fukao, T., Song, X.-Q., Aoyama, T., IJlst, L., Ruiter, J., Wanders, R. J. A., Kondo, N. <strong>Molecular basis of very long chain acyl-CoA dehydrogenase deficiency in three Israeli patients: identification of a complex mutant allele with P65L and K247Q mutations, the former being an exonic mutation causing exon 3 skipping.</strong> Hum. Mutat. 15: 430-438, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790204/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790204</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<430::AID-HUMU4>3.0.CO;2-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10790204">Watanabe et al. (2000)</a> found homozygosity for a complex mutant allele with pro65-to-leu (P65L) and lys247-to-gln (K247Q) mutations in the ACADVL gene. The K247Q mutation resulted from a 937A-C transversion. The P65L mutation resulted in the skipping of exon 3. The nucleotide substitution causing the P65L amino acid change was a 194C-T transition located 11 bases upstream of the normal splice donor site of intron 3. This is an example of an exonic mutation that affects exon splicing; a similar situation had been described in the ACAT1 gene (see <a href="/entry/203750#0009">203750.0009</a>). RT-PCR showed 2 cDNA fragments of different sizes. One had the expected size and the other was shorter by 66 basepairs. In the case of P65L, the amino acid change did not reduce enzyme activity, whereas the K247Q mutation reduced it drastically. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790204" 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="0012" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0012 VLCAD DEFICIENCY</strong>
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</span>
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</h4>
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ACADVL, PHE458LEU
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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> rs118204017 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204017;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/rs118204017?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=rs118204017" 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=rs118204017" 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=RCV000001699 OR RCV001731269 OR RCV003914796" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001699, RCV001731269, RCV003914796" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001699...</a>
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<p>In a patient with VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#4" class="mim-tip-reference" title="Cox, G. F., Souri, M., Aoyama, T., Rockenmacher, S., Varvogli, L., Rohr, F., Hashimoto, T., Korson, M. S. <strong>Reversal of severe hypertrophic cardiomyopathy and excellent neuropsychologic outcome in very-long-chain acyl-coenzyme A dehydrogenase deficiency.</strong> J. Pediat. 133: 247-253, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709714</a>] [<a href="https://doi.org/10.1016/s0022-3476(98)70228-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9709714">Cox et al. (1998)</a> identified a 1372T-C transition in the ACADVL gene, resulting in a phe458-to-leu (F458L) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9709714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 VLCAD DEFICIENCY</strong>
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ACADVL, ALA416THR
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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> rs118204018 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204018;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/rs118204018?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=rs118204018" 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=rs118204018" 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=RCV000001700" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001700" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001700</a>
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<p>In a 14-year-old Japanese girl with very mild manifestations of VLCAD deficiency (<a href="/entry/201475">201475</a>), <a href="#8" class="mim-tip-reference" title="Fukao, T., Watanabe, H., Orii, K. E., Takahashi, Y., Hirano, A., Kondo, T., Yamaguchi, S., Aoyama, T., Kondo, N. <strong>Myopathic form of very-long chain acyl-CoA dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.</strong> Pediat. Res. 49: 227-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11158518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11158518</a>] [<a href="https://doi.org/10.1203/00006450-200102000-00016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11158518">Fukao et al. (2001)</a> identified compound heterozygosity for 2 mutations in the ACADVL gene: 1 resulting in an ala416-to-thr (A416T) substitution, and the other resulting in an arg450-to-his (R450H; <a href="#0014">609575.0014</a>) substitution. In vitro functional expression studies showed that both mutant proteins retained residual activity at 30 degrees Celsius. <a href="#8" class="mim-tip-reference" title="Fukao, T., Watanabe, H., Orii, K. E., Takahashi, Y., Hirano, A., Kondo, T., Yamaguchi, S., Aoyama, T., Kondo, N. <strong>Myopathic form of very-long chain acyl-CoA dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.</strong> Pediat. Res. 49: 227-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11158518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11158518</a>] [<a href="https://doi.org/10.1203/00006450-200102000-00016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11158518">Fukao et al. (2001)</a> concluded that the temperature-sensitive mild mutations resulted in the milder phenotype in this patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11158518" 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="0014" class="mim-anchor"></a>
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<strong>.0014 VLCAD DEFICIENCY</strong>
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ACADVL, ARG450HIS
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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> rs118204016 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118204016;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/rs118204016?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=rs118204016" 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=rs118204016" 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=RCV000001701 OR RCV000724571 OR RCV001003625" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001701, RCV000724571, RCV001003625" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001701...</a>
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<span class="mim-text-font">
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<p>For discussion of the arg450-to-his (R450H) substitution in the ACADVL gene that was found in compound heterozygous state in a Japanese patient with VLCAD deficiency by <a href="#8" class="mim-tip-reference" title="Fukao, T., Watanabe, H., Orii, K. E., Takahashi, Y., Hirano, A., Kondo, T., Yamaguchi, S., Aoyama, T., Kondo, N. <strong>Myopathic form of very-long chain acyl-CoA dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.</strong> Pediat. Res. 49: 227-231, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11158518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11158518</a>] [<a href="https://doi.org/10.1203/00006450-200102000-00016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11158518">Fukao et al. (2001)</a>, see <a href="#0013">609575.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11158518" 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="references"class="mim-anchor"></a>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Andresen1996" class="mim-anchor"></a>
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Andresen, B. S., Bross, P., Vianey-Saban, C., Divry, P., Zabot, M.-T., Roe, C. R., Nada, M. A., Byskov, A., Kruse, T. A., Neve, S., Kristiansen, K., Knudsen, I., Corydon, M. J., Gregersen, N.
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<strong>Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene.</strong>
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Hum. Molec. Genet. 5: 461-472, 1996. Note: Erratum: Hum. Molec. Genet. 5: 1390 only, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/5.4.461" target="_blank">Full Text</a>]
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<a id="Aoyama1995" class="mim-anchor"></a>
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Aoyama, T., Souri, M., Ueno, I., Kamijo, T., Yamaguchi, S., Rhead, W. J., Tanaka, K., Hashimoto, T.
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<strong>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</strong>
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Am. J. Hum. Genet. 57: 273-283, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7668252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7668252</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7668252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Aoyama1995" class="mim-anchor"></a>
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Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T.
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<strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong>
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J. Clin. Invest. 95: 2465-2473, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7769092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7769092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7769092" 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/10.1172/JCI117947" target="_blank">Full Text</a>]
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<a id="Cox1998" class="mim-anchor"></a>
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Cox, G. F., Souri, M., Aoyama, T., Rockenmacher, S., Varvogli, L., Rohr, F., Hashimoto, T., Korson, M. S.
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<strong>Reversal of severe hypertrophic cardiomyopathy and excellent neuropsychologic outcome in very-long-chain acyl-coenzyme A dehydrogenase deficiency.</strong>
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J. Pediat. 133: 247-253, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9709714" 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/s0022-3476(98)70228-8" target="_blank">Full Text</a>]
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Cox, K. B., Hamm, D. A., Millington, D. S., Matern, D., Vockley, J., Rinaldo, P., Pinkert, C. A., Rhead, W. J., Lindsey, J. R., Wood, P. A.
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<strong>Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse.</strong>
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Hum. Molec. Genet. 10: 2069-2077, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11590124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11590124</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11590124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/10.19.2069" target="_blank">Full Text</a>]
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<a id="Evans2016" class="mim-anchor"></a>
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Evans, M., Andresen, B. S., Nation, J., Boneh, A.
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<strong>VLCAD deficiency: follow-up and outcome of patients diagnosed through newborn screening in Victoria.</strong>
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Molec. Genet. Metab. 118: 282-287, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27246109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27246109</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27246109" 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.ymgme.2016.05.012" target="_blank">Full Text</a>]
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<a id="Exil2003" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1161/01.RES.0000088786.19197.E4" target="_blank">Full Text</a>]
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<strong>Myopathic form of very-long chain acyl-CoA dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.</strong>
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[<a href="https://doi.org/10.1203/00006450-200102000-00016" target="_blank">Full Text</a>]
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<strong>Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy.</strong>
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[<a href="https://doi.org/10.1086/522375" target="_blank">Full Text</a>]
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<strong>Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10077518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10077518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10077518" 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/10.1161/01.cir.99.10.1337" target="_blank">Full Text</a>]
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Orii, K. O., Saito-Ohara, F., Ikeuchi, T., Orii, T., Kondo, N., Aoyama, T., Hashimoto, T.
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<strong>Assignment of the gene for very-long-chain acyl-CoA dehydrogenase (Acadvl) to mouse chromosome band 11B2-B5 by in situ hybridization.</strong>
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Cytogenet. Cell Genet. 78: 25-26, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9345900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9345900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9345900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000134619" target="_blank">Full Text</a>]
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<a id="Pena2016" class="mim-anchor"></a>
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Pena, L. D. M., van Calcar, S. C., Hansen, J., Edick, M. J., Vockley, C. W., Leslie, N., Cameron, C., Mohsen, A.-W., Berry, S. A., Arnold, G. L., Vockley, J.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27209629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27209629</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27209629" 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.ymgme.2016.05.007" target="_blank">Full Text</a>]
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Smelt, A. H. M., Poorthuis, B. J. H. M., Onkenhout, W., Scholte, H. R., Andresen, B. S., van Duinen, S. G., Gregersen, N., Wintzen, A. R.
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Ann. Neurol. 43: 540-544, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9546340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9546340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9546340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.410430422" target="_blank">Full Text</a>]
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<strong>Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients.</strong>
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<strong>Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.</strong>
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Proc. Nat. Acad. Sci. 92: 10496-10500, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479827/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479827</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7479827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.92.23.10496" target="_blank">Full Text</a>]
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Watanabe, H., Orii, K. E., Fukao, T., Song, X.-Q., Aoyama, T., IJlst, L., Ruiter, J., Wanders, R. J. A., Kondo, N.
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<strong>Molecular basis of very long chain acyl-CoA dehydrogenase deficiency in three Israeli patients: identification of a complex mutant allele with P65L and K247Q mutations, the former being an exonic mutation causing exon 3 skipping.</strong>
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Hum. Mutat. 15: 430-438, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790204/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790204</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790204" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<430::AID-HUMU4>3.0.CO;2-1" target="_blank">Full Text</a>]
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Zhang, L.-F., Ding, J.-H., Yang, B.-Z., He, G.-C., Roe, C.
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<strong>Characterization of the bidirectional promoter region between the human genes encoding VLCAD and PSD-95.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14611808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14611808</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14611808" 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/s0888-7543(03)00211-8" target="_blank">Full Text</a>]
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Zhou, C., Blumberg, B.
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<strong>Overlapping gene structure of human VLCAD and DLG4.</strong>
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Gene 305: 161-166, 2003.
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[<a href="https://doi.org/10.1016/s0378-1119(02)01235-0" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Ada Hamosh - updated : 12/08/2016
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Patricia A. Hartz - updated : 10/8/2009<br>Victor A. McKusick - updated : 11/28/2007
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Cassandra L. Kniffin : 9/12/2005
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carol : 05/22/2017<br>alopez : 12/08/2016<br>carol : 03/28/2016<br>carol : 2/13/2012<br>carol : 5/3/2011<br>terry : 5/2/2011<br>mgross : 10/12/2009<br>mgross : 10/12/2009<br>terry : 10/8/2009<br>terry : 6/6/2008<br>alopez : 11/29/2007<br>terry : 11/28/2007<br>carol : 9/22/2005<br>ckniffin : 9/14/2005
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ACYL-CoA DEHYDROGENASE, VERY LONG-CHAIN; ACADVL
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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VLCAD
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ACADVL</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 237997005;
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<strong>ICD10CM:</strong> E71.310;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 17p13.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:7,217,125-7,225,266 </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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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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17p13.1
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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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VLCAD deficiency
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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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201475
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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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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<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>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 ACADVL gene encodes very long-chain acyl-CoA dehydrogenase (VLCAD) (EC 1.3.99.13). VLCAD is unique among the acyl-CoA dehydrogenases in its size, structure, and intramitochondrial distribution (Aoyama et al., 1995). </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>Izai et al. (1992) identified and purified a novel acyl-CoA dehydrogenase, Acadvl, from rat liver mitochondria. </p><p>Aoyama et al. (1995) cloned and sequenced 2 overlapping cDNA clones corresponding to human mitochondrial VLCAD. The cDNA encodes a 655-amino acid protein with a 40-amino acid leader peptide, yielding a mature 615-residue protein. </p><p>Whereas the other acyl-CoA dehydrogenases are homotetramers of a 43- to 45-kD subunit, VLCAD purified from human liver was shown by Aoyama et al. (1995) to be a 154-kD homodimer of a 70-kD subunit. VLCAD was loosely bound to the mitochondrial inner membrane and required detergent for stabilization. In contrast, the other 3 acyl-CoA dehydrogenases others were readily extractable into the soluble fraction without detergent, indicating that they are located in the mitochondrial matrix. </p><p>Andresen et al. (1996) isolated cDNA clones for human VLCAD by using rat Vlcad cDNA sequences to identify an EST from human fetal brain in the GenBank database, followed by 5-prime and 3-prime rapid amplification of cDNA ends (RACE) to identify overlapping clones. Sequence analysis of the coding region and the 5-prime noncoding region of the VLCAD cDNA showed no differences with the sequence published by Aoyama et al. (1995). Andresen et al. (1996) found 26 to 33% homology between VLCAD and other human acyl-CoA dehydrogenases. Northern blot analysis detected a 2.4-kb mRNA transcript in a variety of human tissues. </p><p>By real-time RT-PCR, Zhou and Blumberg (2003) detected VLCAD expression in all tissues examined, with highest expression in heart and skeletal muscle, followed by placenta and pancreas. </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>Izai et al. (1992) found that the properties of Acadvl purified from rat liver mitochondria differed from those of the short (ACADS; 606885)-, medium (ACADM; 607008)-, and long (ACADL; 609576)-chain acyl-CoA dehydrogenases. Acadvl was active toward very long-chain fatty acids. </p><p>Aoyama et al. (1995) found that human VLCAD had 10 times higher specific activity toward palmitoyl-CoA than did LCAD. The enzyme was found to catalyze the major part of mitochondrial palmitoyl-CoA dehydrogenation in liver, heart, skeletal muscle, and skin fibroblasts. </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">
|
|
<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>Strauss et al. (1995) determined that the ACADVL gene contains 20 exons. The ACADVL gene is about 5.4 kb long (Zhou and Blumberg, 2003). </p><p>Zhang et al. (2003) noted that the VLCAD and the DLG4 (602887) genes are located in a head-to-head orientation on chromosome 17p. The transcribed regions of the 2 genes overlap by about 220 bp. Using serial promoter partial deletion constructs in a reporter gene assay, they found that the essential promoter activity of DLG4 is carried within a region of about 400 bp and covers the entire VLCAD minimal promoter, which spans about 270 bp. The results from di-(2-ethylhexyl) phthalate (DEHP)-treated HepG2 cells revealed that the minimal VLCAD promoter can upregulate VLCAD expression in response to DEHP treatment. Site-directed mutagenesis experiments showed that a mutated AP2 (107580)-binding site markedly reduced the transcriptional activity of both the VLCAD and DLG4 promoters and abolished the minimal VLCAD promoter's response to DEHP treatment. </p><p>Independently, Zhou and Blumberg (2003) determined that the VLCAD and DLG4 genes overlap. The 2 genes share 245 nucleotides at their 5-prime ends, and the transcription start site for DLG4 extends into the coding region of VLCAD exon 1. The upstream regions of the VLCAD and DLG4 genes, including the overlapping region, contain 2 potential TATA-less promoters with potential binding sites for several common transcription factors. RT-PCR detected unique patterns of expression for VLCAD and DLG4, indicating that, although they share common regulatory elements, VLCAD and DLG4 also have distinct tissue-specific elements. The mouse Dlg4 and Vlcad genes are oriented in a head-to-head manner, but they do not overlap and are separated by almost 3.5 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">
|
|
<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">
|
|
<p>Andresen et al. (1996) mapped the ACADVL gene to human chromosome 17p13.1-p11.2 by analysis of rodent-human hybrids. </p><p>By fluorescence in situ hybridization, Orii et al. (1997) mapped the murine Acadvl gene to chromosome 11 in a region of synteny to human 17p13. </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">
|
|
<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">
|
|
<p>In cultured fibroblasts of 2 patients with VLCAD deficiency (201475), Aoyama et al. (1995) identified a 105-bp deletion in the ACADVL gene (609575.0001). </p><p>Andresen et al. (1996) identified 9 different mutations in the ACADVL gene in 4 unrelated patients with VLCAD deficiency. Two patients carried 3 different mutations. Different mutations were observed in each of the patients. Western blot analysis on fibroblasts from 3 of the patients revealed severe quantitative reduction in VLCAD protein. </p><p>Mathur et al. (1999) identified 21 different mutations in the ACADVL gene in 18 of 37 children with cardiomyopathy, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis. Sixty-seven percent of children had severe dilated or hypertrophic cardiomyopathy at presentation. In 7 patients, only 1 mutation was found despite direct sequencing of all exons. Missense, frameshift, and splice consensus sequence mutations were seen, as well as in-frame deletions. Eighty percent of these mutations were associated with cardiomyopathy. The authors concluded that infantile cardiomyopathy is the most common clinical phenotype for VLCAD deficiency and highlighted the marked allelic heterogeneity in this disorder. </p><p>Since VLCAD-deficient patients frequently harbor missense mutations with unpredictable effects on enzyme activity, Gobin-Limballe et al. (2007) investigated the response to bezafibrate as a function of genotype in 33 VLCAD-deficient fibroblast cell lines representing 45 different mutations. Treatment with bezafibrate (400 microM for 48 hours) resulted in a marked increase in FAO capacities, often leading to restoration of normal values, for 21 genotypes that mainly corresponded to patients with the myopathic phenotype. In contrast, bezafibrate induced no changes in FAO for 11 genotypes corresponding to severe neonatal or infantile phenotypes. This pattern of response was not due to differential inductions of VLCAD mRNA, as shown by quantitative real-time PCR, but reflected variable increases in measured VLCAD residual enzyme activity in response to bezafibrate. Genotype cross-analysis allowed the identification of alleles carrying missense mutations, which could account for these different pharmacologic profiles and, on this basis, led to the characterization of 9 mild and 11 severe missense mutations. The responses to bezafibrate reflected the severity of the metabolic blockage in various genotypes, which appeared to be correlated with the phenotype. This study emphasized the potential of bezafibrate, a widely prescribed hypolipidemic drug, for the correction of VLCAD deficiency and exemplified the integration of molecular information in a therapeutic strategy. </p><p>Of the 52 patients with VLCAD deficiency reported by Pena et al. (2016), molecular testing was available for 46. Two mutations were identified in 44 of these while only 1 mutation was identified in the remaining 2. Most (38 of 46, 83%) were compound heterozygous, and of the 50 different alleles reported, 26 were novel. Evans et al. (2016) reported 5 novel mutations among 22 patients with VLCAD deficiency identified in Victoria, Australia. </p>
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|
</span>
|
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<div>
|
|
<br />
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|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Cox et al. (2001) generated mice with VLCAD deficiency (Vlcad -/-) and compared their pathologic and biochemical phenotypes to mice with Lcad deficiency (Lcad -/-) and wildtype mice. Vlcad -/- mice had milder fatty acid change in liver and heart. Dehydrogenation of various acyl-CoA substrates by liver, heart, and skeletal muscle mitochondria differed among the 3 genotypes. The results for liver were most informative as Vlcad -/- mice had a reduction in activity toward palmitoyl-CoA and oleoyl-CoA (58% and 64% of wildtype, respectively), whereas Lcad -/- mice showed a more profoundly reduced activity toward these substrates (35% and 32% of wildtype, respectively), with a significant reduction of activity toward the branched chain substrate 2,6-dimethylheptanoyl-CoA. C16 and C18 acylcarnitines were elevated in bile, blood, and serum of fasted Vlcad -/- mice, whereas abnormally elevated C12 and C14 acylcarnitines were prominent in Lcad -/- mice. Progeny with the combined Lcad +/+//Vlcad +/- genotype were overrepresented in offspring from sires and dams heterozygous for both Lcad and Vlcad mutations. In contrast, no live mice with a compound Lcad -/-/Vlcad -/- genotype were detected, suggesting that this genotype may be lethal in utero or in the periparturient period. </p><p>To define the onset and molecular mechanism of myocardial disease, Exil et al. (2003) generated Vlcad-deficient mice by homologous recombination. They found that Vlcad-deficient hearts had microvesicular lipid accumulation and marked mitochondrial proliferation, and demonstrated facilitated induction of polymorphic ventricular tachycardia, without antecedent stress. The expression of acyl-CoA synthetase-1 (ACS1; 152425), adipophilin, Ap2, cytochrome c, and the peroxisome proliferator-activated receptor-gamma coactivator-1 (PPARGC1; 604517) were increased immediately after birth, preceding overt histologic lipidosis, whereas Acs1 expression was markedly downregulated in the adult heart. Exil et al. (2003) concluded that mice with Vlcad deficiency have altered expression of a variety of genes in the fatty acid metabolic pathway from birth, reflecting metabolic feedback circuits, with progression to ultrastructural and physiologic correlates of the associated human disease in the absence of stress. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>14 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 VLCAD DEFICIENCY</strong>
|
|
</span>
|
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</h4>
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</div>
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<div>
|
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<span class="mim-text-font">
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ACADVL, 105-BP DEL
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<br />
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SNP: rs2142981921,
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ClinVar: RCV000001688
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 2 patients with VLCAD deficiency (201475), Aoyama et al. (1995) identified a 105-bp deletion encompassing bases 1078-1182 in the VLCAD cDNA. The deletion was thought to result from exon skipping and was predicted to result in the in-frame deletion of 35 amino acids, beginning with val360 of the precursor VLCAD. Using the vaccinia viral system, Aoyama et al. (1995) performed quantitative cDNA expression of normal human VLCAD in the patients' fibroblasts and demonstrated that raising VLCAD activity to approximately 20% of normal control fibroblast activity raised palmitic acid beta-oxidation flux to the level found in control fibroblasts. The mutation described in these patients has consequences for enzyme folding and assembly that are similar to those for the well-characterized A985G mutation (lys329-to-glu; 607008.0001) found in approximately 90% of the mutant alleles in patients with MCAD deficiency (201450). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 VLCAD DEFICIENCY</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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ACADVL, IVS11DS, G-A, +1
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<br />
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SNP: rs113690956,
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gnomAD: rs113690956,
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ClinVar: RCV000001689, RCV000210824
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|
|
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|
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</span>
|
|
</div>
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with VLCAD deficiency (201475) associated with infantile cardiomyopathy and sudden death, Strauss et al. (1995) identified a homozygous G-to-A transition in the consensus dinucleotide of the donor splice site in intron 11 of the ACADVL gene, resulting in the skipping of exon 11. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 VLCAD DEFICIENCY</strong>
|
|
</span>
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</h4>
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</div>
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<div>
|
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<span class="mim-text-font">
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ACADVL, ARG613TRP
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<br />
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|
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SNP: rs118204014,
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gnomAD: rs118204014,
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ClinVar: RCV000001690, RCV000185733
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a patient with VLCAD deficiency (201475), Souri et al. (1996) identified compound heterozygosity for 2 mutations in the ACADVL gene: a 1837C-T transition, resulting in an arg613-to-trp (R613W) substitution, and a 135-bp deletion of nucleotides 343-477, resulting in the loss of 45 amino acids from the VLCAD protein (609575.0005). </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0004 VLCAD DEFICIENCY</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ACADVL, IVS5AS, 1-BP DEL, G, -1
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<br />
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ClinVar: RCV000001691, RCV000077915, RCV003128226
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with VLCAD deficiency (201475) associated with infantile cardiomyopathy and sudden death, Strauss et al. (1995) identified compound heterozygosity for 2 mutations in the ACADVL gene: R613W (609575.0003) and a 1-bp deletion of one of the 2 guanine nucleotides forming the intron-exon 6 boundary. The normal sequence is ccccagGAA and the mutant sequence was cccaGAA. The authors noted that the most likely consequence of this deletion would be an alternation in splicing because of loss of the conserved ag dinucleotide at the splice acceptor site. Alternatively, splicing at this site might occur but this would result in loss of a single nucleotide in exon 6, causing a shift in the mRNA reading frame. In either event, this mutation would most likely result in an unstable mRNA and lack of VLCAD protein expression from the mutant allele. </p>
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</span>
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|
</div>
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 VLCAD DEFICIENCY</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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ACADVL, 135-BP DEL
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<br />
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|
|
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SNP: rs387906249,
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|
|
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gnomAD: rs387906249,
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|
|
|
|
|
ClinVar: RCV000001691, RCV000077915, RCV003128226
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of the 135-bp deletion of nucleotides 343-477 in the ACADVL gene, resulting in the loss of 45 amino acids, that was found in compound heterozygous state in a patient with VLCAD deficiency (201475) by Souri et al. (1996), see 609575.0003. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
|
|
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|
</div>
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|
|
<div>
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|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 VLCAD DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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ACADVL, 3-BP DEL, NT388
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<br />
|
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|
|
SNP: rs387906251,
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|
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|
|
|
|
ClinVar: RCV000001693, RCV001596930, RCV003430629
|
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|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with VLCAD deficiency (201475), Souri et al. (1996) identified a homozygous 3-bp deletion in the ACADVL gene (nucleotides 388-390), resulting in deletion of glu130 (E130X). In another patient, Souri et al. (1996) found the 3-bp deletion mutation in compound heterozygosity with the K382Q mutation (609575.0008). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 VLCAD DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ACADVL, 3-BP DEL, NT895
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs387906252,
|
|
|
|
|
|
|
|
ClinVar: RCV000001694, RCV000077926
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant with VLCAD deficiency (201475), Souri et al. (1996) found deletion of nucleotides 895-897 in the ACADVL gene, resulting in deletion of lys299 (K299X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 VLCAD DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ACADVL, LYS382GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204015,
|
|
|
|
|
|
gnomAD: rs118204015,
|
|
|
|
|
|
ClinVar: RCV000001695
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant with VLCAD deficiency (201475), Souri et al. (1996) identified a 1144A-C transversion in the ACADVL gene, resulting in a lys382-to-gln (K382Q) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 VLCAD DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ACADVL, GLY401ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2309689,
|
|
|
|
|
|
gnomAD: rs2309689,
|
|
|
|
|
|
ClinVar: RCV000020072, RCV000077903
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 42-year-old woman with late-onset VLCAD deficiency (201475), Smelt et al. (1998) identified compound heterozygosity for 2 mutations in the ACADVL gene: a G-to-A transition in exon 13, resulting in a gly401-to-asp (G401D) substitution, and a G-to-A transition in exon 14, resulting in an arg410-to-his (R410H; 609575.0010) substitution. The patient had recurrent rhabdomyolysis and markedly elevated levels of tetradecadienoic acid and hexadecadienoic acid. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 VLCAD DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ACADVL, ARG410HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204016,
|
|
|
|
|
|
gnomAD: rs118204016,
|
|
|
|
|
|
ClinVar: RCV000001701, RCV000724571, RCV001003625
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the G-to-A transition in exon 14 of the ACADVL gene, resulting in an arg410-to-his (R410H), that was found in compound heterozygous state in a patient with VLCAD deficiency by Smelt et al. (1998), see 609575.0009. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 VLCAD DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ACADVL, PRO65LEU AND LYS247GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28934585, rs387906253,
|
|
|
|
|
|
gnomAD: rs28934585,
|
|
|
|
|
|
ClinVar: RCV000001698, RCV000020076, RCV000077913, RCV000420053, RCV001250508
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Israeli patient with VLCAD deficiency (201475), Watanabe et al. (2000) found homozygosity for a complex mutant allele with pro65-to-leu (P65L) and lys247-to-gln (K247Q) mutations in the ACADVL gene. The K247Q mutation resulted from a 937A-C transversion. The P65L mutation resulted in the skipping of exon 3. The nucleotide substitution causing the P65L amino acid change was a 194C-T transition located 11 bases upstream of the normal splice donor site of intron 3. This is an example of an exonic mutation that affects exon splicing; a similar situation had been described in the ACAT1 gene (see 203750.0009). RT-PCR showed 2 cDNA fragments of different sizes. One had the expected size and the other was shorter by 66 basepairs. In the case of P65L, the amino acid change did not reduce enzyme activity, whereas the K247Q mutation reduced it drastically. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 VLCAD DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ACADVL, PHE458LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204017,
|
|
|
|
|
|
gnomAD: rs118204017,
|
|
|
|
|
|
ClinVar: RCV000001699, RCV001731269, RCV003914796
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with VLCAD deficiency (201475), Cox et al. (1998) identified a 1372T-C transition in the ACADVL gene, resulting in a phe458-to-leu (F458L) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 VLCAD DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ACADVL, ALA416THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204018,
|
|
|
|
|
|
gnomAD: rs118204018,
|
|
|
|
|
|
ClinVar: RCV000001700
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old Japanese girl with very mild manifestations of VLCAD deficiency (201475), Fukao et al. (2001) identified compound heterozygosity for 2 mutations in the ACADVL gene: 1 resulting in an ala416-to-thr (A416T) substitution, and the other resulting in an arg450-to-his (R450H; 609575.0014) substitution. In vitro functional expression studies showed that both mutant proteins retained residual activity at 30 degrees Celsius. Fukao et al. (2001) concluded that the temperature-sensitive mild mutations resulted in the milder phenotype in this patient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 VLCAD DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ACADVL, ARG450HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118204016,
|
|
|
|
|
|
gnomAD: rs118204016,
|
|
|
|
|
|
ClinVar: RCV000001701, RCV000724571, RCV001003625
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg450-to-his (R450H) substitution in the ACADVL gene that was found in compound heterozygous state in a Japanese patient with VLCAD deficiency by Fukao et al. (2001), see 609575.0013. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Andresen, B. S., Bross, P., Vianey-Saban, C., Divry, P., Zabot, M.-T., Roe, C. R., Nada, M. A., Byskov, A., Kruse, T. A., Neve, S., Kristiansen, K., Knudsen, I., Corydon, M. J., Gregersen, N.
|
|
<strong>Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene.</strong>
|
|
Hum. Molec. Genet. 5: 461-472, 1996. Note: Erratum: Hum. Molec. Genet. 5: 1390 only, 1996.
|
|
|
|
|
|
[PubMed: 8845838]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.4.461]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aoyama, T., Souri, M., Ueno, I., Kamijo, T., Yamaguchi, S., Rhead, W. J., Tanaka, K., Hashimoto, T.
|
|
<strong>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</strong>
|
|
Am. J. Hum. Genet. 57: 273-283, 1995.
|
|
|
|
|
|
[PubMed: 7668252]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R. I., Rhead, W. J., Uetake, K., Tanaka, K., Hashimoto, T.
|
|
<strong>Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.</strong>
|
|
J. Clin. Invest. 95: 2465-2473, 1995.
|
|
|
|
|
|
[PubMed: 7769092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI117947]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, G. F., Souri, M., Aoyama, T., Rockenmacher, S., Varvogli, L., Rohr, F., Hashimoto, T., Korson, M. S.
|
|
<strong>Reversal of severe hypertrophic cardiomyopathy and excellent neuropsychologic outcome in very-long-chain acyl-coenzyme A dehydrogenase deficiency.</strong>
|
|
J. Pediat. 133: 247-253, 1998.
|
|
|
|
|
|
[PubMed: 9709714]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(98)70228-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cox, K. B., Hamm, D. A., Millington, D. S., Matern, D., Vockley, J., Rinaldo, P., Pinkert, C. A., Rhead, W. J., Lindsey, J. R., Wood, P. A.
|
|
<strong>Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse.</strong>
|
|
Hum. Molec. Genet. 10: 2069-2077, 2001.
|
|
|
|
|
|
[PubMed: 11590124]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.19.2069]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Evans, M., Andresen, B. S., Nation, J., Boneh, A.
|
|
<strong>VLCAD deficiency: follow-up and outcome of patients diagnosed through newborn screening in Victoria.</strong>
|
|
Molec. Genet. Metab. 118: 282-287, 2016.
|
|
|
|
|
|
[PubMed: 27246109]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2016.05.012]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Exil, V. J., Roberts, R. L., Sims, H., McLaughlin, J. E., Malkin, R. A., Gardner, C. D., Ni, G., Rottman, J. N., Strauss, A. W.
|
|
<strong>Very-long-chain acyl-coenzyme A dehydrogenase deficiency in mice.</strong>
|
|
Circ. Res. 93: 448-455, 2003.
|
|
|
|
|
|
[PubMed: 12893739]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1161/01.RES.0000088786.19197.E4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fukao, T., Watanabe, H., Orii, K. E., Takahashi, Y., Hirano, A., Kondo, T., Yamaguchi, S., Aoyama, T., Kondo, N.
|
|
<strong>Myopathic form of very-long chain acyl-CoA dehydrogenase deficiency: evidence for temperature-sensitive mild mutations in both mutant alleles in a Japanese girl.</strong>
|
|
Pediat. Res. 49: 227-231, 2001.
|
|
|
|
|
|
[PubMed: 11158518]
|
|
|
|
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