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Entry
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- *602292 - ENOYL-CoA HYDRATASE, SHORT-CHAIN, 1, MITOCHONDRIAL; ECHS1
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- OMIM
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<p>
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<span class="h4">*602292</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/602292">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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<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 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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<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=ENSG00000127884;t=ENST00000368547" 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=1892" 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=602292" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<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=ENSG00000127884;t=ENST00000368547" 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_004092" 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_004092" 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=602292" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=03799&isoform_id=03799_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/ECHS1" 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/433413,1922287,14286220,30583085,62906863,119581743,194097323,308219096" 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/P30084" 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=1892" 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=ENSG00000127884;t=ENST00000368547" 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=ECHS1" 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=ECHS1" 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+1892" 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/ECHS1" 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:1892" 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/1892" 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=chr10&hgg_gene=ENST00000368547.4&hgg_start=133362485&hgg_end=133373354&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3151" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602292[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=602292[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/ECHS1/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/ENSG00000127884" 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=ECHS1" 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=ECHS1" 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=ECHS1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ECHS1&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/PA27597" 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:3151" 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/FBgn0033879.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:2136460" 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/ECHS1#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:2136460" 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/1892/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1892" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001155;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001155 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001156;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001156 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-030616-617" 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="mimCellLines">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:602292" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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:1892" 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=ECHS1&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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</div>
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<div>
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
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602292
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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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ENOYL-CoA HYDRATASE, SHORT-CHAIN, 1, MITOCHONDRIAL; ECHS1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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SHORT-CHAIN ENOYL-CoA HYDRATASE; SCEH
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ECHS1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ECHS1</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/10/680?start=-3&limit=10&highlight=680">10q26.3</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:133362485-133373354&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'})">10:133,362,485-133,373,354</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
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<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>
|
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<th>
|
|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/10/680?start=-3&limit=10&highlight=680">
|
|
10q26.3
|
|
</a>
|
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</span>
|
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</td>
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency
|
|
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616277"> 616277 </a>
|
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|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
|
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</tr>
|
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</tbody>
|
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</table>
|
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</div>
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<p>The ECHS1 gene encodes short-chain enoyl-CoA hydratase (SCEH; <a href="https://enzyme.expasy.org/EC/4.2.1.17" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 4.2.1.17</a>), which catalyzes the second step in mitochondrial fatty acid beta-oxidation (summary by <a href="#5" class="mim-tip-reference" title="Kanazawa, M., Ohtake, A., Abe, H., Yamamoto, S., Satoh, Y., Takayanagi, M., Niimi, H., Mori, M., Hashimoto, T. <strong>Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase.</strong> Enzyme Protein 47: 9-13, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012501</a>] [<a href="https://doi.org/10.1159/000468650" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8012501">Kanazawa et al., 1993</a>). The enzyme is also active in the isoleucine and valine catabolic pathways. In the valine catabolic pathway, ECHS1 acts upstream of HIBCH (<a href="/entry/610690">610690</a>) and converts methacrylyl-CoA to (S)-3-hydroxyisobutyryl-CoA and acryloyl-CoA to 3-hydroxypropionyl-CoA (summary by <a href="#6" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8012501+25125611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By using rat SCEH cDNAs to probe a human liver library, <a href="#5" class="mim-tip-reference" title="Kanazawa, M., Ohtake, A., Abe, H., Yamamoto, S., Satoh, Y., Takayanagi, M., Niimi, H., Mori, M., Hashimoto, T. <strong>Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase.</strong> Enzyme Protein 47: 9-13, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012501</a>] [<a href="https://doi.org/10.1159/000468650" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8012501">Kanazawa et al. (1993)</a> isolated human SCEH cDNAs. The predicted 290-amino acid human protein is 87% identical to that of the rat gene. By Northern blot analysis, <a href="#5" class="mim-tip-reference" title="Kanazawa, M., Ohtake, A., Abe, H., Yamamoto, S., Satoh, Y., Takayanagi, M., Niimi, H., Mori, M., Hashimoto, T. <strong>Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase.</strong> Enzyme Protein 47: 9-13, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012501</a>] [<a href="https://doi.org/10.1159/000468650" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8012501">Kanazawa et al. (1993)</a> found a single 1.6-kb mRNA species transcribed most strongly in human liver, but also in fibroblast and muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8012501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Janssen, U., Davis, E. M., Le Beau, M. M., Stoffel, W. <strong>Human mitochondrial enoyl-CoA hydratase gene (ECHS1): structural organization and assignment to chromosome 10q26.2-q26.3.</strong> Genomics 40: 470-475, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9073515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9073515</a>] [<a href="https://doi.org/10.1006/geno.1996.4597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9073515">Janssen et al. (1997)</a> isolated 2 overlapping genomic clones encompassing the entire human ECHS1 gene. They determined that the ECHS1 gene contains 8 exons and spans 11 kb of genomic DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9073515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Janssen, U., Davis, E. M., Le Beau, M. M., Stoffel, W. <strong>Human mitochondrial enoyl-CoA hydratase gene (ECHS1): structural organization and assignment to chromosome 10q26.2-q26.3.</strong> Genomics 40: 470-475, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9073515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9073515</a>] [<a href="https://doi.org/10.1006/geno.1996.4597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9073515">Janssen et al. (1997)</a> mapped the ECHS1 gene to 10q26.2-q26.3 by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9073515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By analysis of ECHS1 isolated from HEK293 cells, <a href="#10" class="mim-tip-reference" title="Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N. <strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong> J. Med. Genet. 52: 691-698, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26251176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26251176</a>] [<a href="https://doi.org/10.1136/jmedgenet-2015-103231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26251176">Yamada et al. (2015)</a> showed that it had high substrate specificity for crotonyl-CoA and moderate specificity for acryloyl-CoA, 3-methylcrotonyl-CoA, and methacrylyl-CoA. ECHS1 bound to tiglyl-CoA, but hydrated only a small amount of this substrate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26251176" 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="#8" class="mim-tip-reference" title="Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E. <strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong> Am. J. Med. Genet. 185A: 157-167, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.61936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33112498">Simon et al. (2021)</a> identified a synonymous P163P variant in the ECHS1 gene (c.489G-A, <a href="#0013">602292.0013</a>) at an allele frequency of 0.17 in the Samoan population, with 34 homozygotes detected. This frequency did not suggest decreased fitness in individuals with homozygosity for the variant; however, <a href="#8" class="mim-tip-reference" title="Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E. <strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong> Am. J. Med. Genet. 185A: 157-167, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.61936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33112498">Simon et al. (2021)</a> found the variant to be disease causing in families with Samoan ancestry when in trans with a severe mutation on the other ECHS1 allele (e.g., A278T, <a href="/entry/602202#0012">602202.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33112498" 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 infant sibs with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>) manifest as a severe fatal neurodegenerative disorder, <a href="#6" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al. (2014)</a> identified compound heterozygous mutations in the ECHS1 gene (<a href="#0001">602292.0001</a> and <a href="#0002">602292.0002</a>). Patient fibroblasts showed significantly decreased ECHS1 activity and absence of the normal protein by immunoblot analysis. <a href="#6" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al. (2014)</a> postulated that the enzymatic defect caused accumulation of the metabolites methacrylyl-CoA and acryloyl-CoA, which are toxic reactive intermediates that may have caused the brain pathology. Decreased activity of the pyruvate dehydrogenase complex (PDC) may also have been a secondary effect. The metabolic abnormalities in these patients appeared to be confined to the valine pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a boy with ECHS1D, <a href="#7" class="mim-tip-reference" title="Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y. <strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong> Hum. Mutat. 36: 232-239, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>] [<a href="https://doi.org/10.1002/humu.22730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25393721">Sakai et al. (2015)</a> identified compound heterozygous mutations in the ECHS1 gene (<a href="#0003">602292.0003</a> and <a href="#0004">602292.0004</a>). The mutations, which were found by targeted exome sequencing, segregated with the disorder in the family. Patient cells also showed a combined mitochondrial respiratory chain deficiency, which was rescued by expression of wildtype ECHS1. These findings suggested a link between ECHS1 and the mitochondrial respiratory chain. <a href="#7" class="mim-tip-reference" title="Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y. <strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong> Hum. Mutat. 36: 232-239, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>] [<a href="https://doi.org/10.1002/humu.22730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25393721">Sakai et al. (2015)</a> speculated that ECHS1 deficiency induced metabolic abnormalities resulting in the accumulation of toxic metabolites, such as glyoxylate, that secondarily inhibited normal mitochondrial respiratory function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25393721" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 10 unrelated families segregating ECHS1D, <a href="#3" class="mim-tip-reference" title="Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others. <strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong> Ann. Clin. Transl. Neurol. 2: 492-509, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26000322[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/acn3.189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26000322">Haack et al. (2015)</a> identified homozygous or compound heterozygous mutations in the ECHS1 gene. In 1 family (F3), 3 affected sibs (proband 68552), born to consanguineous Pakistani parents, were homozygous for a missense mutation (Q159R; <a href="#0007">602292.0007</a>). In 2 unrelated families (F1 and F10), patient 346 and patient 52236 were compound heterozygous for the Q159R mutation and different second mutations (N59S, <a href="#0005">602292.0005</a> and E77Q, <a href="#0008">602292.0008</a>), respectively. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the mutations in the family. Immunoblotting on fibroblasts from the 2 compound heterozygous patients showed reduced expression of the ECHS1 protein and reduced palmitate-dependent respiration; fibroblasts from 1 of these patients showed reduced 2-enoyl-CoA hydratase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26000322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 patients with ECHS1D from 3 unrelated French Canadian families, <a href="#9" class="mim-tip-reference" title="Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J. <strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong> Hum. Genet. 134: 981-991, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>] [<a href="https://doi.org/10.1007/s00439-015-1577-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26099313">Tetreault et al. (2015)</a> identified compound heterozygous mutations in the ECHS1 gene. Affected members in the 3 families had a T180A missense mutation (<a href="#0009">602292.0009</a>) with a different second mutation (<a href="#0007">602292.0007</a>, <a href="#0010">602292.0010</a> and <a href="#0011">602292.0011</a>). All of the mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. All 4 mutations occurred in the ECHS1 enoyl-CoA hydratase/isomerase domain and were predicted to decrease protein stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26099313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 Irish Traveler sibs and a Pakistani patient with ECHS1D, <a href="#2" class="mim-tip-reference" title="Fitzsimons, P. E., Alston, C. L., Bonnen, P. E., Hughes, J., Crushell, E., Geraghty, M. T., Tetreault, M., O'Reilly, P., Twomey, E., Sheikh, Y., Walsh, R., Waterham, H. R., Ferdinandusse, S., Wanders, R. J. A., Taylor, R. W., Pitt, J. J., Mayne, P. D. <strong>Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.</strong> Am. J. Med. Genet. 176A: 1115-1127, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29575569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29575569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29575569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.38658" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29575569">Fitzsimons et al. (2018)</a> identified homozygosity for the previously identified Q159R and T180A mutations in the ECHS1 gene, respectively. Erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid were elevated on urine organic acids of all patients. Muscle and fibroblast testing was carried out in 1 sib and the Pakistani patient. Fibroblasts showed markedly decreased ECHS1 enzyme activity and absence of ECHS1 on Western blot analysis. PDH activity and beta oxidation studies were normal. Activities of respiratory chain complexes I, II, and IV were normal, and activity of complexes II+III was decreased in muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29575569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 patients, including 3 sibs, from 2 families with ECHS1D, <a href="#8" class="mim-tip-reference" title="Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E. <strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong> Am. J. Med. Genet. 185A: 157-167, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.61936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33112498">Simon et al. (2021)</a> identified compound heterozygous mutations in the ECHS1 gene (A278T, <a href="#0012">602292.0012</a> and P163P, <a href="#0013">602292.0013</a>). ECHS1 protein expression and activity were reduced in fibroblasts from the carrier parents from family 1 and reduced to a greater degree in their affected offspring. ECHS1 protein expression and activity were also reduced in fibroblasts from the patient in family 2. In both families, a Samoan parent was the carrier of the P163P variant. Analysis of mRNA from fibroblasts from the unaffected mother from family 1, who was homozygous for the P163P variant, and from one of her affected children demonstrated that the P163P variant resulted in abnormal splicing with skipping of exon 4. Family 1 was previously reported by <a href="#1" class="mim-tip-reference" title="Abdenur, J. E., Sowa, M., Simon, M., Steenari, M., Skaar, J., Eftekharian, S., Chang, R., Ferdinandusse, S., Pitt, J. <strong>Medical nutrition therapy in patients with HIBCH and ECHS1 defects: clinical and biochemical response to low valine diet.</strong> Molec. Genet. Metab. Rep. 24: 100617, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32642440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32642440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32642440[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgmr.2020.100617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32642440">Abdenur et al. (2020)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=32642440+33112498" 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>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>13 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602292[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<p>In 2 sibs with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>), <a href="#6" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al. (2014)</a> identified compound heterozygous mutations in the ECHS1 gene: a c.473C-A transversion in exon 4, resulting in an ala158-to-asp (A158D) substitution at a highly conserved residue at the entrance of the substrate-binding pocket of the enzyme; and a G-to-C transversion in intron 3 (c.414+3G-C; <a href="#0002">602292.0002</a>), resulting in a splicing defect and generation of a mutant protein lacking amino acids 126-138 at the interface between the 2 trimers of the hexameric structure.The mutations, which were found by direct sequencing of the ECHS1 gene based on biochemical abnormalities found in the patients, segregated with the disorder in the family and were not found in the dbSNP or Exome Variant Server databases. Patient fibroblasts showed significantly decreased ECHS1 activity and absence of the normal protein by immunoblot analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>For discussion of the c.414+3G-C mutation in the ECHS1 gene that was found in compound heterozygous state in patients with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>) by <a href="#6" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al. (2014)</a>, see <a href="#0001">602292.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125611" 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> rs587776497 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776497;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/rs587776497?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=rs587776497" 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=rs587776497" 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=RCV000144496 OR RCV000167581 OR RCV002515942" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144496, RCV000167581, RCV002515942" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144496...</a>
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<p>In a patient with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>), <a href="#7" class="mim-tip-reference" title="Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y. <strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong> Hum. Mutat. 36: 232-239, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>] [<a href="https://doi.org/10.1002/humu.22730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25393721">Sakai et al. (2015)</a> identified compound heterozygous mutations in the ECHS1 gene: a c.2T-G transversion, resulting in a met1-to-arg (M1R) substitution in the initiation codon,and a c.5C-T transition, resulting in an ala2-to-val (A2V; <a href="#0004">602292.0004</a>) substitution. Both mutations occurred in the mitochondrial transit peptide. The mutations, which were found by targeted exome sequencing and confirmed by Sanger sequencing, were filtered against the dbSNP (build 135) and 1000 Genomes Project databases, and segregated with the disorder in the family. Patient skeletal muscle cells showed severely decreased expression of ECHS1 and decreased activity (13%) of control values. Patient cells also showed a combined mitochondrial respiratory chain deficiency of complexes I, IV, and V, and these defects were rescued by expression of wildtype ECHS1. These findings suggested a link between ECHS1 and the mitochondrial respiratory chain. <a href="#7" class="mim-tip-reference" title="Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y. <strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong> Hum. Mutat. 36: 232-239, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>] [<a href="https://doi.org/10.1002/humu.22730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25393721">Sakai et al. (2015)</a> speculated that ECHS1 deficiency induced metabolic abnormalities including accumulation of toxic metabolites, such as glyoxylate, that secondarily inhibited normal mitochondrial respiratory function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25393721" 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> rs587776498 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776498;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/rs587776498?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=rs587776498" 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=rs587776498" 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=RCV000144497 OR RCV000167582 OR RCV000481050" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144497, RCV000167582, RCV000481050" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144497...</a>
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<p>For discussion of the ala2-to-val (A2V) mutation in the ECHS1 gene that was found in compound heterozygous state in a patient with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>) by <a href="#7" class="mim-tip-reference" title="Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y. <strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong> Hum. Mutat. 36: 232-239, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>] [<a href="https://doi.org/10.1002/humu.22730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25393721">Sakai et al. (2015)</a>, see <a href="#0003">602292.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25393721" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs201865375 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201865375;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/rs201865375?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=rs201865375" 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=rs201865375" 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=RCV000203238 OR RCV001387132 OR RCV004748657" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000203238, RCV001387132, RCV004748657" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000203238...</a>
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<p>In 2 sibs, born of unrelated Japanese parents, with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>), <a href="#10" class="mim-tip-reference" title="Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N. <strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong> J. Med. Genet. 52: 691-698, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26251176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26251176</a>] [<a href="https://doi.org/10.1136/jmedgenet-2015-103231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26251176">Yamada et al. (2015)</a> identified compound heterozygous mutations in the ECHS1 gene: a c.176A-G transition, resulting in an asn59-to-ser (N59S) substitution, and a c.413C-T transition, resulting in an ala138-to-val (A138V; <a href="#0006">602292.0006</a>) substitution. The mutations, which were found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the family. Western blot analysis of patient fibroblasts showed severely decreased levels of ECHS1 protein with normal levels of mRNA, suggesting that the mutant protein is unstable. ECHS1 activity towards different substrates was decreased to between 2.6% and 6.2% of normal controls. In vitro functional expression studies showed that the D59S mutant was nonfunctional, whereas the A138V mutant had about 30% residual activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26251176" 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>For discussion of the N59S mutation in the ECHS1 gene that was found in compound heterozygous state in a patient (patient 346, family 1) with ECHS1D by <a href="#3" class="mim-tip-reference" title="Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others. <strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong> Ann. Clin. Transl. Neurol. 2: 492-509, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26000322[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/acn3.189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26000322">Haack et al. (2015)</a>, see <a href="#0007">602292.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26000322" 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 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs864309656 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs864309656;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/rs864309656?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=rs864309656" 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=rs864309656" 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=RCV000203246" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000203246" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000203246</a>
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<p>For discussion of the c.413C-T transition in the ECHS1 gene, resulting in an ala138-to-val (A138V) substitution, that was found in compound heterozygous state in sibs with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>) by <a href="#10" class="mim-tip-reference" title="Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N. <strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong> J. Med. Genet. 52: 691-698, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26251176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26251176</a>] [<a href="https://doi.org/10.1136/jmedgenet-2015-103231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26251176">Yamada et al. (2015)</a>, see <a href="#0005">602292.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26251176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs375032130 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs375032130;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/rs375032130?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=rs375032130" 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=rs375032130" 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=RCV000432904 OR RCV000578268 OR RCV002252122" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000432904, RCV000578268, RCV002252122" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000432904...</a>
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<p>In 3 sibs (proband 68552) with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>), who were born to consanguineous Pakistani parents (family 3), <a href="#3" class="mim-tip-reference" title="Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others. <strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong> Ann. Clin. Transl. Neurol. 2: 492-509, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26000322[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/acn3.189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26000322">Haack et al. (2015)</a> identified a homozygous c.476A-G transition (c.476A-G, NM_004092.3) in exon 4 of the ECHS1 gene, resulting in a gln159-to-arg (Q159R) substitution. The mutation was identified by whole-exome sequencing in 1 sib and confirmed by Sanger sequencing from blood spots in the 2 other sibs (identical female twins), who were deceased. The parents were heterozygous for the mutation. <a href="#3" class="mim-tip-reference" title="Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others. <strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong> Ann. Clin. Transl. Neurol. 2: 492-509, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26000322[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/acn3.189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26000322">Haack et al. (2015)</a> identified the Q159R mutation in compound heterozygosity with different ECHS1 mutations in 2 unrelated patients with ECHS1D: patient 346 (family 1) had the previously identified N9S mutation (<a href="#0005">602292.0005</a>) and patient 52236 (family 10) had a c.229G-C transversion, resulting in a glu77-to-gln (E77Q; <a href="#0009">602292.0009</a>) substitution. Immunoblot analysis on fibroblasts from patients 346 and 52236 showed reduced expression of the ECHS1 protein; reduced palmitate-dependent respiration and reduced 2-enoyl-CoA hydratase activity was found in the fibroblasts of patient 52236. The Q159R variant had an allele frequency of 0.0001148 in the ExAC database, and the E77Q was not present in the database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26000322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 Irish Traveler sibs with ECHS1D, <a href="#2" class="mim-tip-reference" title="Fitzsimons, P. E., Alston, C. L., Bonnen, P. E., Hughes, J., Crushell, E., Geraghty, M. T., Tetreault, M., O'Reilly, P., Twomey, E., Sheikh, Y., Walsh, R., Waterham, H. R., Ferdinandusse, S., Wanders, R. J. A., Taylor, R. W., Pitt, J. J., Mayne, P. D. <strong>Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.</strong> Am. J. Med. Genet. 176A: 1115-1127, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29575569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29575569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29575569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.38658" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29575569">Fitzsimons et al. (2018)</a> identified homozygosity for the Q159R mutation in the ECHS1 gene. Erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid were elevated on urine organic acids of all patients. Muscle and fibroblast testing was carried out in 1 sib. Fibroblasts showed markedly decreased ECHS1 enzyme activity and absence of ECHS1 on Western blot analysis. PDH activity and beta oxidation studies were normal. Activities of respiratory chain complexes I, II, and IV were normal, and activity of complexes II+III was decreased in muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29575569" 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>For discussion of the Q159R mutation in the ESCHS1 gene that was found in compound heterozygosity in a patient (P4) with ESCHS1D by <a href="#9" class="mim-tip-reference" title="Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J. <strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong> Hum. Genet. 134: 981-991, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>] [<a href="https://doi.org/10.1007/s00439-015-1577-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26099313">Tetreault et al. (2015)</a>, see <a href="#0009">602292.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26099313" 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> rs1426014295 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1426014295;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/rs1426014295?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=rs1426014295" 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=rs1426014295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the c.229G-C transversion (c.229G-C, NM_004092.3) in the ECHS1 gene, resulting in a glu77-to-gln (E77Q) substitution, that was found in compound heterozygous state in a patient with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>) by <a href="#3" class="mim-tip-reference" title="Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others. <strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong> Ann. Clin. Transl. Neurol. 2: 492-509, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26000322[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/acn3.189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26000322">Haack et al. (2015)</a>, see <a href="#0007">602292.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26000322" 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> rs557128093 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs557128093;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/rs557128093?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=rs557128093" 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=rs557128093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 4 patients from 3 unrelated French Canadian families with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>), <a href="#9" class="mim-tip-reference" title="Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J. <strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong> Hum. Genet. 134: 981-991, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>] [<a href="https://doi.org/10.1007/s00439-015-1577-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26099313">Tetreault et al. (2015)</a> identified compound heterozygous mutations in the ECHS1 gene. All patients had a c.538A-G transition (c.538A-G, NM_004092) in exon 5, resulting in a thr180-to-ala (T180A) substitution; in patient 1 (P1), the second mutation was a c.583G-A transition in exon 5, resulting in a gly195-to-ser (G195S; <a href="#0010">602292.0010</a>) substitution; in 2 sibs (P2 and P3), the second mutation was a c.713C-T transition in exon 6, resulting in an ala238-to-val (A238V; <a href="#0011">602292.0011</a>) substitution; and in P4, the second mutation was Q159R (<a href="#0007">602292.0007</a>). The mutations segregated with the disorder in the families. All of the mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. None of these variants were present in the 1000 Genomes Project, Exome Variant Server, or dbSNP (build 138) databases, except for Q159R, which was reported once in EVS. All 4 mutations were in the ECHS1 enoyl-CoA hydratase/isomerase domain and were predicted to decrease protein stability. <a href="#9" class="mim-tip-reference" title="Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J. <strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong> Hum. Genet. 134: 981-991, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>] [<a href="https://doi.org/10.1007/s00439-015-1577-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26099313">Tetreault et al. (2015)</a> found that the patients with the T180A variant shared a common haplotype, suggesting that the variant derives from a single ancestral mutation. The haplotype was not observed in 10 unrelated French Canadian control samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26099313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Pakistani patient with ECHS1D, <a href="#2" class="mim-tip-reference" title="Fitzsimons, P. E., Alston, C. L., Bonnen, P. E., Hughes, J., Crushell, E., Geraghty, M. T., Tetreault, M., O'Reilly, P., Twomey, E., Sheikh, Y., Walsh, R., Waterham, H. R., Ferdinandusse, S., Wanders, R. J. A., Taylor, R. W., Pitt, J. J., Mayne, P. D. <strong>Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.</strong> Am. J. Med. Genet. 176A: 1115-1127, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29575569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29575569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29575569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.38658" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29575569">Fitzsimons et al. (2018)</a> identified homozygosity for the T180A mutation. Erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid were elevated on urine organic acids. Patient fibroblasts showed markedly decreased ECHS1 enzyme activity and absence of ECHS1 on Western blot analysis. PDH activity and beta oxidation studies were normal. Activities of respiratory chain complexes I, II, and IV were normal, and activity of complexes II+III was decreased in muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29575569" 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> rs761989177 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs761989177;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/rs761989177?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=rs761989177" 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=rs761989177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the c.583G-A transition (c.583G-C, NM_004092) in exon 5 of the ECHS1 gene, resulting in a gly195-to-ser (G195S) substitution, that was found in a patient (P1) with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>) by <a href="#9" class="mim-tip-reference" title="Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J. <strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong> Hum. Genet. 134: 981-991, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>] [<a href="https://doi.org/10.1007/s00439-015-1577-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26099313">Tetreault et al. (2015)</a>, see <a href="#0009">602292.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26099313" 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> rs200584793 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200584793;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/rs200584793?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=rs200584793" 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=rs200584793" 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=RCV001248826 OR RCV001574497" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001248826, RCV001574497" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001248826...</a>
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<p>For discussion of the c.713C-T transition (c.713C-T, NM_004092) in exon 6 of the ECHS1 gene, resulting in an ala238-to-val (A238V) substitution, that was found in 2 sibs (P2 and P3) with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>) by <a href="#9" class="mim-tip-reference" title="Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J. <strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong> Hum. Genet. 134: 981-991, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>] [<a href="https://doi.org/10.1007/s00439-015-1577-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26099313">Tetreault et al. (2015)</a>, see <a href="#0009">602292.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26099313" 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> rs933592081 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs933592081;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/rs933592081?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=rs933592081" 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=rs933592081" 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=RCV001569068 OR RCV004774460" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001569068, RCV004774460" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001569068...</a>
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<p>In 4 patients, including 3 sibs, from 2 families with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>), <a href="#8" class="mim-tip-reference" title="Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E. <strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong> Am. J. Med. Genet. 185A: 157-167, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.61936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33112498">Simon et al. (2021)</a> identified compound heterozygous mutations in the ECHS1 gene: a c.832G-A transition (c.832G-A, NM_004092), resulting in an ala278-to-thr (A278T) substitution, and a c.489G-A transition (<a href="#0013">602292.0013</a>), resulting in a pro163-to-pro (P163P) synonymous change leading to a splicing abnormality. The mutations were identified by whole-exome sequencing, whole-genome sequencing, and Sanger sequencing of cDNA, and segregated with disease in both families. In both families, the P163P variant was inherited from a Samoan parent. The A278T variant was present in the gnomAD database (v2.1.1) at an allele frequency of 6.5x10(-5) in the South Asian population and 7.7x10(-7) in the European non-Finnish population, and the P163P mutation was present at an allele frequency of 0.001 in the overall population and 0.01 in the East Asian population with 2 homozygotes reported. ECHS1 protein expression and enzyme activity were reduced in fibroblasts from the unaffected carrier parents from family 1 and reduced to a greater degree in their affected offspring. ECHS1 protein expression and activity were also reduced in fibroblasts from the patient in family 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33112498" 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 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
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ECHS1, c.489G-A (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs140410716;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs140410716</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs140410716 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs140410716;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/rs140410716?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=rs140410716" 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=rs140410716" 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=RCV000427574 OR RCV000894199 OR RCV002272235 OR RCV003922780" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000427574, RCV000894199, RCV002272235, RCV003922780" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000427574...</a>
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<p>For discussion of the c.489G-A transition (c.489G-A, NM_004092) in the ECHS1 gene, resulting in a pro163-to-pro (P163P) synonymous change leading to a splicing abnormality, that was identified in compound heterozygous state in 4 patients, including 3 sibs, from 2 families with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; <a href="/entry/616277">616277</a>) by <a href="#8" class="mim-tip-reference" title="Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E. <strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong> Am. J. Med. Genet. 185A: 157-167, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.61936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33112498">Simon et al. (2021)</a>, see <a href="#0012">602292.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33112498" 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>REFERENCES</strong>
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Abdenur, J. E., Sowa, M., Simon, M., Steenari, M., Skaar, J., Eftekharian, S., Chang, R., Ferdinandusse, S., Pitt, J.
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<strong>Medical nutrition therapy in patients with HIBCH and ECHS1 defects: clinical and biochemical response to low valine diet.</strong>
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Molec. Genet. Metab. Rep. 24: 100617, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32642440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32642440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32642440[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32642440" 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.ymgmr.2020.100617" target="_blank">Full Text</a>]
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Fitzsimons, P. E., Alston, C. L., Bonnen, P. E., Hughes, J., Crushell, E., Geraghty, M. T., Tetreault, M., O'Reilly, P., Twomey, E., Sheikh, Y., Walsh, R., Waterham, H. R., Ferdinandusse, S., Wanders, R. J. A., Taylor, R. W., Pitt, J. J., Mayne, P. D.
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<strong>Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.</strong>
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Am. J. Med. Genet. 176A: 1115-1127, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29575569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29575569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29575569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29575569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.38658" target="_blank">Full Text</a>]
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Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others.
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<strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong>
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Ann. Clin. Transl. Neurol. 2: 492-509, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26000322[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26000322" 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/acn3.189" target="_blank">Full Text</a>]
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</p>
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</li>
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<li>
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<a id="4" class="mim-anchor"></a>
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<a id="Janssen1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Janssen, U., Davis, E. M., Le Beau, M. M., Stoffel, W.
|
|
<strong>Human mitochondrial enoyl-CoA hydratase gene (ECHS1): structural organization and assignment to chromosome 10q26.2-q26.3.</strong>
|
|
Genomics 40: 470-475, 1997.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9073515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9073515</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9073515" 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/10.1006/geno.1996.4597" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Kanazawa1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kanazawa, M., Ohtake, A., Abe, H., Yamamoto, S., Satoh, Y., Takayanagi, M., Niimi, H., Mori, M., Hashimoto, T.
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|
<strong>Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase.</strong>
|
|
Enzyme Protein 47: 9-13, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012501</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8012501" 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/10.1159/000468650" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Peters2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J.
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<strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong>
|
|
Brain 137: 2903-2908, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awu216" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Sakai2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y.
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<strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong>
|
|
Hum. Mutat. 36: 232-239, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25393721" 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/humu.22730" target="_blank">Full Text</a>]
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Simon2021" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E.
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<strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong>
|
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Am. J. Med. Genet. 185A: 157-167, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33112498" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.61936" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Tetreault2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J.
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<strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong>
|
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Hum. Genet. 134: 981-991, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26099313" 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/10.1007/s00439-015-1577-y" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Yamada2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N.
|
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<strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong>
|
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J. Med. Genet. 52: 691-698, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26251176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26251176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26251176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmedgenet-2015-103231" target="_blank">Full Text</a>]
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</p>
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</ol>
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<br />
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</div>
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<a id="contributors" class="mim-anchor"></a>
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 08/05/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 07/13/2020<br>Cassandra L. Kniffin - updated : 12/21/2015<br>Cassandra L. Kniffin - updated : 3/24/2015
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Rebekah S. Rasooly : 1/29/1998
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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="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/06/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/05/2024<br>carol : 08/12/2021<br>carol : 07/14/2020<br>carol : 07/13/2020<br>carol : 12/29/2015<br>ckniffin : 12/21/2015<br>carol : 3/25/2015<br>mcolton : 3/25/2015<br>mcolton : 3/25/2015<br>ckniffin : 3/24/2015<br>carol : 4/15/2014<br>alopez : 1/29/1998
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</span>
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<div class="container visible-print-block">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 602292
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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ENOYL-CoA HYDRATASE, SHORT-CHAIN, 1, MITOCHONDRIAL; ECHS1
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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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SHORT-CHAIN ENOYL-CoA HYDRATASE; SCEH
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ECHS1</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>
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<em>
|
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Cytogenetic location: 10q26.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 10:133,362,485-133,373,354 </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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<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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10q26.3
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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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Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
616277
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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 ECHS1 gene encodes short-chain enoyl-CoA hydratase (SCEH; EC 4.2.1.17), which catalyzes the second step in mitochondrial fatty acid beta-oxidation (summary by Kanazawa et al., 1993). The enzyme is also active in the isoleucine and valine catabolic pathways. In the valine catabolic pathway, ECHS1 acts upstream of HIBCH (610690) and converts methacrylyl-CoA to (S)-3-hydroxyisobutyryl-CoA and acryloyl-CoA to 3-hydroxypropionyl-CoA (summary by Peters et al., 2014). </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">
|
|
<p>By using rat SCEH cDNAs to probe a human liver library, Kanazawa et al. (1993) isolated human SCEH cDNAs. The predicted 290-amino acid human protein is 87% identical to that of the rat gene. By Northern blot analysis, Kanazawa et al. (1993) found a single 1.6-kb mRNA species transcribed most strongly in human liver, but also in fibroblast and muscle. </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">
|
|
<p>Janssen et al. (1997) isolated 2 overlapping genomic clones encompassing the entire human ECHS1 gene. They determined that the ECHS1 gene contains 8 exons and spans 11 kb of genomic DNA. </p>
|
|
</span>
|
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Janssen et al. (1997) mapped the ECHS1 gene to 10q26.2-q26.3 by fluorescence in situ hybridization. </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>By analysis of ECHS1 isolated from HEK293 cells, Yamada et al. (2015) showed that it had high substrate specificity for crotonyl-CoA and moderate specificity for acryloyl-CoA, 3-methylcrotonyl-CoA, and methacrylyl-CoA. ECHS1 bound to tiglyl-CoA, but hydrated only a small amount of this substrate. </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>Population Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Simon et al. (2021) identified a synonymous P163P variant in the ECHS1 gene (c.489G-A, 602292.0013) at an allele frequency of 0.17 in the Samoan population, with 34 homozygotes detected. This frequency did not suggest decreased fitness in individuals with homozygosity for the variant; however, Simon et al. (2021) found the variant to be disease causing in families with Samoan ancestry when in trans with a severe mutation on the other ECHS1 allele (e.g., A278T, 602202.0012). </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">
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|
<p>In 2 infant sibs with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277) manifest as a severe fatal neurodegenerative disorder, Peters et al. (2014) identified compound heterozygous mutations in the ECHS1 gene (602292.0001 and 602292.0002). Patient fibroblasts showed significantly decreased ECHS1 activity and absence of the normal protein by immunoblot analysis. Peters et al. (2014) postulated that the enzymatic defect caused accumulation of the metabolites methacrylyl-CoA and acryloyl-CoA, which are toxic reactive intermediates that may have caused the brain pathology. Decreased activity of the pyruvate dehydrogenase complex (PDC) may also have been a secondary effect. The metabolic abnormalities in these patients appeared to be confined to the valine pathway. </p><p>In a boy with ECHS1D, Sakai et al. (2015) identified compound heterozygous mutations in the ECHS1 gene (602292.0003 and 602292.0004). The mutations, which were found by targeted exome sequencing, segregated with the disorder in the family. Patient cells also showed a combined mitochondrial respiratory chain deficiency, which was rescued by expression of wildtype ECHS1. These findings suggested a link between ECHS1 and the mitochondrial respiratory chain. Sakai et al. (2015) speculated that ECHS1 deficiency induced metabolic abnormalities resulting in the accumulation of toxic metabolites, such as glyoxylate, that secondarily inhibited normal mitochondrial respiratory function. </p><p>In 10 unrelated families segregating ECHS1D, Haack et al. (2015) identified homozygous or compound heterozygous mutations in the ECHS1 gene. In 1 family (F3), 3 affected sibs (proband 68552), born to consanguineous Pakistani parents, were homozygous for a missense mutation (Q159R; 602292.0007). In 2 unrelated families (F1 and F10), patient 346 and patient 52236 were compound heterozygous for the Q159R mutation and different second mutations (N59S, 602292.0005 and E77Q, 602292.0008), respectively. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the mutations in the family. Immunoblotting on fibroblasts from the 2 compound heterozygous patients showed reduced expression of the ECHS1 protein and reduced palmitate-dependent respiration; fibroblasts from 1 of these patients showed reduced 2-enoyl-CoA hydratase activity. </p><p>In 4 patients with ECHS1D from 3 unrelated French Canadian families, Tetreault et al. (2015) identified compound heterozygous mutations in the ECHS1 gene. Affected members in the 3 families had a T180A missense mutation (602292.0009) with a different second mutation (602292.0007, 602292.0010 and 602292.0011). All of the mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. All 4 mutations occurred in the ECHS1 enoyl-CoA hydratase/isomerase domain and were predicted to decrease protein stability. </p><p>In 3 Irish Traveler sibs and a Pakistani patient with ECHS1D, Fitzsimons et al. (2018) identified homozygosity for the previously identified Q159R and T180A mutations in the ECHS1 gene, respectively. Erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid were elevated on urine organic acids of all patients. Muscle and fibroblast testing was carried out in 1 sib and the Pakistani patient. Fibroblasts showed markedly decreased ECHS1 enzyme activity and absence of ECHS1 on Western blot analysis. PDH activity and beta oxidation studies were normal. Activities of respiratory chain complexes I, II, and IV were normal, and activity of complexes II+III was decreased in muscle. </p><p>In 4 patients, including 3 sibs, from 2 families with ECHS1D, Simon et al. (2021) identified compound heterozygous mutations in the ECHS1 gene (A278T, 602292.0012 and P163P, 602292.0013). ECHS1 protein expression and activity were reduced in fibroblasts from the carrier parents from family 1 and reduced to a greater degree in their affected offspring. ECHS1 protein expression and activity were also reduced in fibroblasts from the patient in family 2. In both families, a Samoan parent was the carrier of the P163P variant. Analysis of mRNA from fibroblasts from the unaffected mother from family 1, who was homozygous for the P163P variant, and from one of her affected children demonstrated that the P163P variant resulted in abnormal splicing with skipping of exon 4. Family 1 was previously reported by Abdenur et al. (2020). </p>
|
|
</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>13 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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|
ECHS1, ALA158ASP
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|
<br />
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|
|
|
SNP: rs786204001,
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|
|
|
|
ClinVar: RCV000167579
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277), Peters et al. (2014) identified compound heterozygous mutations in the ECHS1 gene: a c.473C-A transversion in exon 4, resulting in an ala158-to-asp (A158D) substitution at a highly conserved residue at the entrance of the substrate-binding pocket of the enzyme; and a G-to-C transversion in intron 3 (c.414+3G-C; 602292.0002), resulting in a splicing defect and generation of a mutant protein lacking amino acids 126-138 at the interface between the 2 trimers of the hexameric structure.The mutations, which were found by direct sequencing of the ECHS1 gene based on biochemical abnormalities found in the patients, segregated with the disorder in the family and were not found in the dbSNP or Exome Variant Server databases. Patient fibroblasts showed significantly decreased ECHS1 activity and absence of the normal protein by immunoblot analysis. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
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|
<div>
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ECHS1, IVS3DS, G-C, +3
|
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|
|
<br />
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|
|
|
SNP: rs786204002,
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|
|
|
|
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|
|
ClinVar: RCV000167580
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.414+3G-C mutation in the ECHS1 gene that was found in compound heterozygous state in patients with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277) by Peters et al. (2014), see 602292.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ECHS1, MET1ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776497,
|
|
|
|
|
|
gnomAD: rs587776497,
|
|
|
|
|
|
ClinVar: RCV000144496, RCV000167581, RCV002515942
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277), Sakai et al. (2015) identified compound heterozygous mutations in the ECHS1 gene: a c.2T-G transversion, resulting in a met1-to-arg (M1R) substitution in the initiation codon,and a c.5C-T transition, resulting in an ala2-to-val (A2V; 602292.0004) substitution. Both mutations occurred in the mitochondrial transit peptide. The mutations, which were found by targeted exome sequencing and confirmed by Sanger sequencing, were filtered against the dbSNP (build 135) and 1000 Genomes Project databases, and segregated with the disorder in the family. Patient skeletal muscle cells showed severely decreased expression of ECHS1 and decreased activity (13%) of control values. Patient cells also showed a combined mitochondrial respiratory chain deficiency of complexes I, IV, and V, and these defects were rescued by expression of wildtype ECHS1. These findings suggested a link between ECHS1 and the mitochondrial respiratory chain. Sakai et al. (2015) speculated that ECHS1 deficiency induced metabolic abnormalities including accumulation of toxic metabolites, such as glyoxylate, that secondarily inhibited normal mitochondrial respiratory function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ECHS1, ALA2VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776498,
|
|
|
|
|
|
gnomAD: rs587776498,
|
|
|
|
|
|
ClinVar: RCV000144497, RCV000167582, RCV000481050
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ala2-to-val (A2V) mutation in the ECHS1 gene that was found in compound heterozygous state in a patient with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277) by Sakai et al. (2015), see 602292.0003. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ECHS1, ASN59SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs201865375,
|
|
|
|
|
|
gnomAD: rs201865375,
|
|
|
|
|
|
ClinVar: RCV000203238, RCV001387132, RCV004748657
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born of unrelated Japanese parents, with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277), Yamada et al. (2015) identified compound heterozygous mutations in the ECHS1 gene: a c.176A-G transition, resulting in an asn59-to-ser (N59S) substitution, and a c.413C-T transition, resulting in an ala138-to-val (A138V; 602292.0006) substitution. The mutations, which were found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the family. Western blot analysis of patient fibroblasts showed severely decreased levels of ECHS1 protein with normal levels of mRNA, suggesting that the mutant protein is unstable. ECHS1 activity towards different substrates was decreased to between 2.6% and 6.2% of normal controls. In vitro functional expression studies showed that the D59S mutant was nonfunctional, whereas the A138V mutant had about 30% residual activity. </p><p>For discussion of the N59S mutation in the ECHS1 gene that was found in compound heterozygous state in a patient (patient 346, family 1) with ECHS1D by Haack et al. (2015), see 602292.0007. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ECHS1, ALA138VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs864309656,
|
|
|
|
|
|
gnomAD: rs864309656,
|
|
|
|
|
|
ClinVar: RCV000203246
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.413C-T transition in the ECHS1 gene, resulting in an ala138-to-val (A138V) substitution, that was found in compound heterozygous state in sibs with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277) by Yamada et al. (2015), see 602292.0005. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ECHS1, GLN159ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs375032130,
|
|
|
|
|
|
gnomAD: rs375032130,
|
|
|
|
|
|
ClinVar: RCV000432904, RCV000578268, RCV002252122
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs (proband 68552) with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277), who were born to consanguineous Pakistani parents (family 3), Haack et al. (2015) identified a homozygous c.476A-G transition (c.476A-G, NM_004092.3) in exon 4 of the ECHS1 gene, resulting in a gln159-to-arg (Q159R) substitution. The mutation was identified by whole-exome sequencing in 1 sib and confirmed by Sanger sequencing from blood spots in the 2 other sibs (identical female twins), who were deceased. The parents were heterozygous for the mutation. Haack et al. (2015) identified the Q159R mutation in compound heterozygosity with different ECHS1 mutations in 2 unrelated patients with ECHS1D: patient 346 (family 1) had the previously identified N9S mutation (602292.0005) and patient 52236 (family 10) had a c.229G-C transversion, resulting in a glu77-to-gln (E77Q; 602292.0009) substitution. Immunoblot analysis on fibroblasts from patients 346 and 52236 showed reduced expression of the ECHS1 protein; reduced palmitate-dependent respiration and reduced 2-enoyl-CoA hydratase activity was found in the fibroblasts of patient 52236. The Q159R variant had an allele frequency of 0.0001148 in the ExAC database, and the E77Q was not present in the database. </p><p>In 3 Irish Traveler sibs with ECHS1D, Fitzsimons et al. (2018) identified homozygosity for the Q159R mutation in the ECHS1 gene. Erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid were elevated on urine organic acids of all patients. Muscle and fibroblast testing was carried out in 1 sib. Fibroblasts showed markedly decreased ECHS1 enzyme activity and absence of ECHS1 on Western blot analysis. PDH activity and beta oxidation studies were normal. Activities of respiratory chain complexes I, II, and IV were normal, and activity of complexes II+III was decreased in muscle. </p><p>For discussion of the Q159R mutation in the ESCHS1 gene that was found in compound heterozygosity in a patient (P4) with ESCHS1D by Tetreault et al. (2015), see 602292.0009. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ECHS1, GLU77GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1426014295,
|
|
|
|
|
|
gnomAD: rs1426014295,
|
|
|
|
|
|
ClinVar: RCV001248823
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.229G-C transversion (c.229G-C, NM_004092.3) in the ECHS1 gene, resulting in a glu77-to-gln (E77Q) substitution, that was found in compound heterozygous state in a patient with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277) by Haack et al. (2015), see 602292.0007. </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ECHS1, THR180ALA
|
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<br />
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SNP: rs557128093,
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gnomAD: rs557128093,
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ClinVar: RCV000851532, RCV001564785
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</span>
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<span class="mim-text-font">
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<p>In 4 patients from 3 unrelated French Canadian families with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277), Tetreault et al. (2015) identified compound heterozygous mutations in the ECHS1 gene. All patients had a c.538A-G transition (c.538A-G, NM_004092) in exon 5, resulting in a thr180-to-ala (T180A) substitution; in patient 1 (P1), the second mutation was a c.583G-A transition in exon 5, resulting in a gly195-to-ser (G195S; 602292.0010) substitution; in 2 sibs (P2 and P3), the second mutation was a c.713C-T transition in exon 6, resulting in an ala238-to-val (A238V; 602292.0011) substitution; and in P4, the second mutation was Q159R (602292.0007). The mutations segregated with the disorder in the families. All of the mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. None of these variants were present in the 1000 Genomes Project, Exome Variant Server, or dbSNP (build 138) databases, except for Q159R, which was reported once in EVS. All 4 mutations were in the ECHS1 enoyl-CoA hydratase/isomerase domain and were predicted to decrease protein stability. Tetreault et al. (2015) found that the patients with the T180A variant shared a common haplotype, suggesting that the variant derives from a single ancestral mutation. The haplotype was not observed in 10 unrelated French Canadian control samples. </p><p>In a Pakistani patient with ECHS1D, Fitzsimons et al. (2018) identified homozygosity for the T180A mutation. Erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid were elevated on urine organic acids. Patient fibroblasts showed markedly decreased ECHS1 enzyme activity and absence of ECHS1 on Western blot analysis. PDH activity and beta oxidation studies were normal. Activities of respiratory chain complexes I, II, and IV were normal, and activity of complexes II+III was decreased in muscle. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0010 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 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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ECHS1, GLY195SER
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<br />
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SNP: rs761989177,
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gnomAD: rs761989177,
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ClinVar: RCV000988462, RCV003883525
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.583G-A transition (c.583G-C, NM_004092) in exon 5 of the ECHS1 gene, resulting in a gly195-to-ser (G195S) substitution, that was found in a patient (P1) with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277) by Tetreault et al. (2015), see 602292.0009. </p>
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0011 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 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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ECHS1, ALA238VAL
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<br />
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SNP: rs200584793,
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gnomAD: rs200584793,
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ClinVar: RCV001248826, RCV001574497
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.713C-T transition (c.713C-T, NM_004092) in exon 6 of the ECHS1 gene, resulting in an ala238-to-val (A238V) substitution, that was found in 2 sibs (P2 and P3) with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277) by Tetreault et al. (2015), see 602292.0009. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0012 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 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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ECHS1, ALA278THR
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<br />
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SNP: rs933592081,
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gnomAD: rs933592081,
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ClinVar: RCV001569068, RCV004774460
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 patients, including 3 sibs, from 2 families with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277), Simon et al. (2021) identified compound heterozygous mutations in the ECHS1 gene: a c.832G-A transition (c.832G-A, NM_004092), resulting in an ala278-to-thr (A278T) substitution, and a c.489G-A transition (602292.0013), resulting in a pro163-to-pro (P163P) synonymous change leading to a splicing abnormality. The mutations were identified by whole-exome sequencing, whole-genome sequencing, and Sanger sequencing of cDNA, and segregated with disease in both families. In both families, the P163P variant was inherited from a Samoan parent. The A278T variant was present in the gnomAD database (v2.1.1) at an allele frequency of 6.5x10(-5) in the South Asian population and 7.7x10(-7) in the European non-Finnish population, and the P163P mutation was present at an allele frequency of 0.001 in the overall population and 0.01 in the East Asian population with 2 homozygotes reported. ECHS1 protein expression and enzyme activity were reduced in fibroblasts from the unaffected carrier parents from family 1 and reduced to a greater degree in their affected offspring. ECHS1 protein expression and activity were also reduced in fibroblasts from the patient in family 2. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0013 MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 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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ECHS1, c.489G-A ({dbSNP rs140410716})
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<br />
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SNP: rs140410716,
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gnomAD: rs140410716,
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ClinVar: RCV000427574, RCV000894199, RCV002272235, RCV003922780
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.489G-A transition (c.489G-A, NM_004092) in the ECHS1 gene, resulting in a pro163-to-pro (P163P) synonymous change leading to a splicing abnormality, that was identified in compound heterozygous state in 4 patients, including 3 sibs, from 2 families with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D; 616277) by Simon et al. (2021), see 602292.0012. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Abdenur, J. E., Sowa, M., Simon, M., Steenari, M., Skaar, J., Eftekharian, S., Chang, R., Ferdinandusse, S., Pitt, J.
|
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<strong>Medical nutrition therapy in patients with HIBCH and ECHS1 defects: clinical and biochemical response to low valine diet.</strong>
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Molec. Genet. Metab. Rep. 24: 100617, 2020.
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[PubMed: 32642440]
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[Full Text: https://doi.org/10.1016/j.ymgmr.2020.100617]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Fitzsimons, P. E., Alston, C. L., Bonnen, P. E., Hughes, J., Crushell, E., Geraghty, M. T., Tetreault, M., O'Reilly, P., Twomey, E., Sheikh, Y., Walsh, R., Waterham, H. R., Ferdinandusse, S., Wanders, R. J. A., Taylor, R. W., Pitt, J. J., Mayne, P. D.
|
|
<strong>Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.</strong>
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Am. J. Med. Genet. 176A: 1115-1127, 2018.
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|
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[PubMed: 29575569]
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|
|
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[Full Text: https://doi.org/10.1002/ajmg.a.38658]
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</p>
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</li>
|
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<li>
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<p class="mim-text-font">
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Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others.
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<strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong>
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Ann. Clin. Transl. Neurol. 2: 492-509, 2015.
|
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|
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[PubMed: 26000322]
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[Full Text: https://doi.org/10.1002/acn3.189]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Janssen, U., Davis, E. M., Le Beau, M. M., Stoffel, W.
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<strong>Human mitochondrial enoyl-CoA hydratase gene (ECHS1): structural organization and assignment to chromosome 10q26.2-q26.3.</strong>
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Genomics 40: 470-475, 1997.
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[PubMed: 9073515]
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[Full Text: https://doi.org/10.1006/geno.1996.4597]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Kanazawa, M., Ohtake, A., Abe, H., Yamamoto, S., Satoh, Y., Takayanagi, M., Niimi, H., Mori, M., Hashimoto, T.
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<strong>Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase.</strong>
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Enzyme Protein 47: 9-13, 1993.
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[PubMed: 8012501]
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[Full Text: https://doi.org/10.1159/000468650]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J.
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<strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong>
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Brain 137: 2903-2908, 2014.
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[PubMed: 25125611]
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[Full Text: https://doi.org/10.1093/brain/awu216]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y.
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<strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong>
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Hum. Mutat. 36: 232-239, 2015.
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[PubMed: 25393721]
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[Full Text: https://doi.org/10.1002/humu.22730]
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</li>
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<li>
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<p class="mim-text-font">
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Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E.
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<strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong>
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Am. J. Med. Genet. 185A: 157-167, 2021.
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[PubMed: 33112498]
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[Full Text: https://doi.org/10.1002/ajmg.a.61936]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J.
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<strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong>
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Hum. Genet. 134: 981-991, 2015.
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[PubMed: 26099313]
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[Full Text: https://doi.org/10.1007/s00439-015-1577-y]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N.
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<strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong>
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J. Med. Genet. 52: 691-698, 2015.
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[PubMed: 26251176]
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[Full Text: https://doi.org/10.1136/jmedgenet-2015-103231]
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 08/05/2024<br>Hilary J. Vernon - updated : 07/13/2020<br>Cassandra L. Kniffin - updated : 12/21/2015<br>Cassandra L. Kniffin - updated : 3/24/2015
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<span class="mim-text-font">
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Rebekah S. Rasooly : 1/29/1998
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carol : 08/06/2024<br>carol : 08/05/2024<br>carol : 08/12/2021<br>carol : 07/14/2020<br>carol : 07/13/2020<br>carol : 12/29/2015<br>ckniffin : 12/21/2015<br>carol : 3/25/2015<br>mcolton : 3/25/2015<br>mcolton : 3/25/2015<br>ckniffin : 3/24/2015<br>carol : 4/15/2014<br>alopez : 1/29/1998
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