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Entry
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- *608801 - GLUTARYL-CoA DEHYDROGENASE; GCDH
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*608801</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608801">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000105607;t=ENST00000222214" 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=2639" 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=608801" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000105607;t=ENST00000222214" 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_000159,NM_013976,NR_102316,NR_102317" 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_000159" 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=608801" 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=01977&isoform_id=01977_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/GCDH" 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/1549327,1905909,2316112,2492631,4503943,7669494,8170719,12803505,30582251,119604730,119604731,119604732,158261837,194374755,194383082,194385004,353453162,943351094,1104767342,1104767652,1104767664,1104767676,1104767683,1104767692,1104767703,1104767712,1104767721,1104767730,1104767738,1104767748,1104767758,1104767769,1104767781,1104767790,1104767799,1104767808,1109182187,1109182189,1346446750,1346446752,1346446754,1346446756,1346446758,1346446760,1346446762,1346446764,1346446766,1346446768,1346446770,1346446772,1346446774,1346446776,1346446778,1346446780,1346446782" 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/Q92947" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=2639" 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=ENSG00000105607;t=ENST00000222214" 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=GCDH" 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=GCDH" 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+2639" 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/GCDH" 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:2639" 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/2639" 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=chr19&hgg_gene=ENST00000222214.10&hgg_start=12891129&hgg_end=12899999&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:4189" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:4189" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/gcdh" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608801[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=608801[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/GCDH/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/ENSG00000105607" 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=GCDH" 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=GCDH" 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=GCDH" 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=GCDH&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/PA28604" 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:4189" 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/FBgn0031824.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:104541" 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/GCDH#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:104541" 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/2639/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=2639" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00010052;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1855" 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:608801" 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:2639" 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=GCDH&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 360416003<br />
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<strong>ICD10CM:</strong> E72.3<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
608801
|
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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>
|
|
<span class="mim-font">
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GLUTARYL-CoA DEHYDROGENASE; GCDH
|
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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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<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=GCDH" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GCDH</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/19/342?start=-3&limit=10&highlight=342">19p13.13</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:12891129-12899999&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'})">19:12,891,129-12,899,999</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
|
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</div>
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<div>
|
|
<br />
|
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</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>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/342?start=-3&limit=10&highlight=342">
|
|
19p13.13
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Glutaricaciduria, type I
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/231670"> 231670 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
|
</td>
|
|
|
|
|
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</tr>
|
|
|
|
|
|
</tbody>
|
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</table>
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<p>Glutaryl-CoA dehydrogenase (GCDH; <a href="https://enzyme.expasy.org/EC/1.3.8.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.3.8.6</a>) is an acyl dehydrogenase involved in the metabolism of lysine, hydroxylysine, and tryptophan. Specifically, it is responsible for the dehydrogenation and decarboxylation of glutaryl-CoA to crotonyl-CoA in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. The active enzyme exists as a homotetramer in the mitochondrial matrix.</p>
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<p><a href="#18" class="mim-tip-reference" title="Lenich, A. C., Goodman, S. I. <strong>The purification and characterization of glutaryl-coenzyme A dehydrogenase from porcine and human liver.</strong> J. Biol. Chem. 261: 4090-4096, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3081514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3081514</a>]" pmid="3081514">Lenich and Goodman (1986)</a> purified the glutaryl-CoA dehydrogenase protein from porcine and human liver mitochondria. <a href="#8" class="mim-tip-reference" title="Goodman, S. I., Kratz, L. E., Frerman, F. E. <strong>Pork and human cDNAs encoding glutaryl-CoA dehydrogenase. In: Coates, P. M.; Tanaka, K. (eds.): New Developments in Fatty Acid Oxidation.</strong> New York: Wiley-Liss 1992. Pp. 169-173."None>Goodman et al. (1992)</a> and <a href="#7" class="mim-tip-reference" title="Goodman, S. I., Kratz, L. E., DiGiulio, K. A., Biery, B. J., Goodman, K. E., Isaya, G., Frerman, F. E. <strong>Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli.</strong> Hum. Molec. Genet. 4: 1493-1498, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541831</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1493" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541831">Goodman et al. (1995)</a> cloned and sequenced a human GCDH cDNA. <a href="#7" class="mim-tip-reference" title="Goodman, S. I., Kratz, L. E., DiGiulio, K. A., Biery, B. J., Goodman, K. E., Isaya, G., Frerman, F. E. <strong>Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli.</strong> Hum. Molec. Genet. 4: 1493-1498, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541831</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1493" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541831">Goodman et al. (1995)</a> found that the cDNA encodes a 438-amino acid precursor protein and a 394-amino acid mature protein with a molecular mass of 43.3 kD. The protein shares 92% sequence identity with its porcine homolog. Alternative splicing between exons 10 and 11 produces 2 GCDH mRNA transcripts, only 1 of which is enzymatically active. The precursor protein undergoes 1-step cleavage by mitochondrial processing peptidase to form the mature GCDH subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3081514+8541831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Koeller, D. M., DiGiulio, K. A., Angeloni, S. V., Dowler, L. L., Frerman, F. E., White, R. A., Goodman, S. I. <strong>Cloning, structure, and chromosome localization of the mouse glutaryl-CoA dehydrogenase gene.</strong> Genomics 28: 508-512, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7490088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7490088</a>] [<a href="https://doi.org/10.1006/geno.1995.1182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7490088">Koeller et al. (1995)</a> showed that the mouse Gcdh cDNA encodes a predicted protein of 438 amino acids which is highly conserved with respect to the pig and human sequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7490088" 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="#3" class="mim-tip-reference" title="Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I. <strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong> Am. J. Hum. Genet. 59: 1006-1011, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900227</a>]" pmid="8900227">Biery et al. (1996)</a> determined that GCDH gene contains 11 exons and spans approximately 7 kb. <a href="#20" class="mim-tip-reference" title="Schwartz, M., Christensen, E., Superti-Furga, A., Brandt, N. J. <strong>The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and 13 novel mutations causing glutaric aciduria type I.</strong> Hum. Genet. 102: 452-458, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600243</a>] [<a href="https://doi.org/10.1007/s004390050720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600243">Schwartz et al. (1998)</a> reported the sequence of introns 1-3 and 6-9 of the GCDH gene, as well as parts of introns 4, 5, and 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9600243+8900227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Koeller, D. M., DiGiulio, K. A., Angeloni, S. V., Dowler, L. L., Frerman, F. E., White, R. A., Goodman, S. I. <strong>Cloning, structure, and chromosome localization of the mouse glutaryl-CoA dehydrogenase gene.</strong> Genomics 28: 508-512, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7490088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7490088</a>] [<a href="https://doi.org/10.1006/geno.1995.1182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7490088">Koeller et al. (1995)</a> determined that the mouse gene contains 11 exons and spans about 7 kb of genomic DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7490088" 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 in situ hybridization and somatic cell hybrid analysis, <a href="#10" class="mim-tip-reference" title="Greenberg, C. R., Duncan, A. M. V., Gregory, C. A., Singal, R., Goodman, S. I. <strong>Assignment of human glutaryl-CoA dehydrogenase gene (GCDH) to the short arm of chromosome 19 (19p13.2) by in situ hybridization and somatic cell hybrid analysis.</strong> Genomics 21: 289-290, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8088809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8088809</a>] [<a href="https://doi.org/10.1006/geno.1994.1264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8088809">Greenberg et al. (1994)</a> mapped the GCDH gene to chromosome 19p13.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8088809" 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>Using interspecific backcross mapping, <a href="#14" class="mim-tip-reference" title="Koeller, D. M., DiGiulio, K. A., Angeloni, S. V., Dowler, L. L., Frerman, F. E., White, R. A., Goodman, S. I. <strong>Cloning, structure, and chromosome localization of the mouse glutaryl-CoA dehydrogenase gene.</strong> Genomics 28: 508-512, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7490088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7490088</a>] [<a href="https://doi.org/10.1006/geno.1995.1182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7490088">Koeller et al. (1995)</a> mapped the mouse gene to chromosome 8 within a region that has homology of synteny to human chromosome 19. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7490088" 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 a Navajo child with glutaric acidemia type I (GA1; <a href="/entry/231670">231670</a>), <a href="#2" class="mim-tip-reference" title="Biery, B. J., Goodman, S. I. <strong>Mutation in glutaryl-CoA dehydrogenase (GCDH) in glutaric acidemia type I. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A165, 1992."None>Biery and Goodman (1992)</a> and <a href="#7" class="mim-tip-reference" title="Goodman, S. I., Kratz, L. E., DiGiulio, K. A., Biery, B. J., Goodman, K. E., Isaya, G., Frerman, F. E. <strong>Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli.</strong> Hum. Molec. Genet. 4: 1493-1498, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541831</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1493" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541831">Goodman et al. (1995)</a> identified homozygosity for a mutation in the GCDH gene (<a href="#0001">608801.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541831" 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>Among 64 unrelated patients with glutaric acidemia type I, <a href="#3" class="mim-tip-reference" title="Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I. <strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong> Am. J. Hum. Genet. 59: 1006-1011, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900227</a>]" pmid="8900227">Biery et al. (1996)</a> identified 12 mutations and several polymorphisms in 7 exons of the GCDH gene (see, e.g., <a href="#0007">608801.0007</a>-<a href="#0009">608801.0009</a>). Several mutations were found in more than one patient, but no one prevalent mutation was detected in the general population. However, a single mutation was found as the cause of glutaric acidemia in the Old Order Amish of Lancaster County, Pennsylvania (A421V; <a href="#0002">608801.0002</a>). <a href="#3" class="mim-tip-reference" title="Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I. <strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong> Am. J. Hum. Genet. 59: 1006-1011, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900227</a>]" pmid="8900227">Biery et al. (1996)</a> expressed several mutations in Escherichia coli; all produced diminished enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900227" 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>Among 8 families with glutaric acidemia I diagnosed in Israel, 6 of Muslim origin and 2 of non-Ashkenazi Jewish background, <a href="#1" class="mim-tip-reference" title="Anikster, Y., Shaag, A., Joseph, A., Mandel, H., Ben-Zeev, B., Christensen, E., Elpeleg, O. N. <strong>Glutaric aciduria type I in the Arab and Jewish communities in Israel.</strong> Am. J. Hum. Genet. 59: 1012-1018, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900228</a>]" pmid="8900228">Anikster et al. (1996)</a> identified 7 mutations in the GCDH gene (see, e.g., <a href="#0003">608801.0003</a>). The molecular basis for the clinical variability in GA I families was not revealed by these findings. <a href="#1" class="mim-tip-reference" title="Anikster, Y., Shaag, A., Joseph, A., Mandel, H., Ben-Zeev, B., Christensen, E., Elpeleg, O. N. <strong>Glutaric aciduria type I in the Arab and Jewish communities in Israel.</strong> Am. J. Hum. Genet. 59: 1012-1018, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900228</a>]" pmid="8900228">Anikster et al. (1996)</a> stated that the occurrence of multiple novel alleles in a small geographic area was explained by their recent origin in isolated communities with a high consanguinity rate. In 5 of the families included in this study, the diagnosis of GA I in the index case was followed by identification of another affected sib, who was either asymptomatic, suffered from a milder form of the disease, or was misdiagnosed for a nonmetabolic condition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Schwartz, M., Christensen, E., Superti-Furga, A., Brandt, N. J. <strong>The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and 13 novel mutations causing glutaric aciduria type I.</strong> Hum. Genet. 102: 452-458, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600243</a>] [<a href="https://doi.org/10.1007/s004390050720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600243">Schwartz et al. (1998)</a> reported 21 different mutations in the GCDH gene found in a total of 20 patients with glutaric acidemia type I. These mutations accounted for 38 of 40 mutant alleles in this population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Goodman, S. I., Stein, D. E., Schlesinger, S., Christensen, E., Schwartz, M., Greenberg, C. R., Elpeleg, O. N. <strong>Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations.</strong> Hum. Mutat. 12: 141-144, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9711871/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9711871</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)12:3<141::AID-HUMU1>3.0.CO;2-K" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9711871">Goodman et al. (1998)</a> reviewed 63 mutations in the GCDH gene that had been identified by several laboratories as the cause of glutaric acidemia I, 30 of them for the first time. They also reported data on expression in E. coli and the relationship to the clinical and biochemical phenotype. No common GCDH mutation was found, and little if any relationship between genotype and clinical phenotype could be recognized. The mutations were widely distributed through the gene, with the largest number in exon 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9711871" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Zschocke, J., Quak, E., Guldberg, P., Hoffmann, G. F. <strong>Mutation analysis in glutaric aciduria type I.</strong> J. Med. Genet. 37: 177-181, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10699052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10699052</a>] [<a href="https://doi.org/10.1136/jmg.37.3.177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10699052">Zschocke et al. (2000)</a> reported a denaturing gradient gel electrophoresis (DGGE) method for detection of mutations in the GCDH gene. Using this method, they found mutations in both alleles in 48 individuals with confirmed GCDH deficiency. No mutations were found in individuals with clinical suspicion of GCDH deficiency but normal enzyme levels. They identified a total of 38 different mutations; 27 were found in single patients, and 21 mutations were previously unreported. Fourteen mutations involved CpG sites. R402W (<a href="#0004">608801.0004</a>) was the most common mutation in Europeans, accounting for 40% of alleles in patients of German origin. <a href="#24" class="mim-tip-reference" title="Zschocke, J., Quak, E., Guldberg, P., Hoffmann, G. F. <strong>Mutation analysis in glutaric aciduria type I.</strong> J. Med. Genet. 37: 177-181, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10699052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10699052</a>] [<a href="https://doi.org/10.1136/jmg.37.3.177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10699052">Zschocke et al. (2000)</a> concluded that the high sensitivity of this method allowed for rapid and cost-efficient diagnosis of glutaricaciduria type I in instances where enzyme analyses are not available or feasible. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10699052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Busquets, C., Merinero, B., Christensen, E., Gelpi, J. L., Campistol, J., Pineda, M., Fernandez-Alvarez, E., Prats, J. M., Sans, A., Arteaga, R., Marti, M., Campos, J., Martinez-Pardo, M., Martinez-Bermejo, A., Ruiz-Falco, M. L., Vaquerizo, J., Orozco, M., Ugarte, M., Coll, M. J., Ribes, A. <strong>Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct.</strong> Pediat. Res. 48: 315-322, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10960496/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10960496</a>] [<a href="https://doi.org/10.1203/00006450-200009000-00009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10960496">Busquets et al. (2000)</a> identified 13 novel and 10 known GCDH mutations in a population of 43 Spanish patients with GA I representing 2 genetically and biochemically distinct groups. Mutations A293T (<a href="#0007">608801.0007</a>) and R402W (<a href="#0004">608801.0004</a>) were common (30% and 28%, respectively) in 23 patients with typical biochemical findings, whereas mutations V400M (<a href="#0008">608801.0008</a>) and R227P (<a href="#0009">608801.0009</a>) (combined frequency of 53%) were only found in the 17 patients with normal glutarate and mild elevation of 3-hydroxyglutarate by urine organic acid analysis. The severity of the clinical phenotype appeared to correlate with encephalopathic crises, but not with residual enzyme activity or genotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10960496" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By GCDH activity assay in transfected baby hamster kidney cells, <a href="#13" class="mim-tip-reference" title="Keyser, B., Muhlhausen, C., Dickmanns, A., Christensen, E., Muschol, N., Ullrich, K., Braulke, T. <strong>Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH).</strong> Hum. Molec. Genet. 17: 3854-3863, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18775954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18775954</a>] [<a href="https://doi.org/10.1093/hmg/ddn284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18775954">Keyser et al. (2008)</a> found that expression of GCDH mutants R138G, R402W (<a href="#0004">608801.0004</a>), and E414K resulted in a complete lack of enzymatic activity. The M264V mutant had 10% residual activity, and Western blot and pulse-chase analysis indicated that the M263V mutant protein was subject to rapid intramitochondrial degradation. The M263V and R402W mutants showed defective homotetrameric assembly. Molecular modeling of mutant GCDH showed that arg138 and glu414 are both located at the bottom of the active site and required for proper arrangement of the ligand, and that the met263 residue on the surface of the protein might be part of the contact interface to interacting proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18775954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By direct sequencing of the GCDH gene in 53 Turkish patients with GA1 from 39 unrelated families, <a href="#12" class="mim-tip-reference" title="Gurbuz, B. B., Yilmaz, D. Y., Coskun, T., Tokath, A., Dursun, A., Sivri, H. S. <strong>Glutaric aciduria type 1: genetic and phenotypic spectrum in 53 patients.</strong> Europ. J. Med. Genet. 63: 104032, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32777384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32777384</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.104032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32777384">Gurbuz et al. (2020)</a> identified mutations in 46 patients, 40 of whom had homozygous mutations. About 85% of the patients were from consanguineous families. Twenty different mutations, 7 of which were novel, were identified, including 17 missense, 2 deletions, and 1 nonsense. The most common mutations were R402W (<a href="#0004">608801.0004</a>), P248L, and L340F, with a frequency of 21.2%, 18.2%, and 12.1%, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32777384" 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>Using CRISPR editing, <a href="#17" class="mim-tip-reference" title="Leandro, J., Dodatko, T., Aten, J., Nemeria, N. S., Zhang, X., Jordan, F., Hendrickson, R. C., Sanchez, R., Yu, C., DeVita, R. J., Houten, S. M. <strong>DHTKD1 and OGDH display substrate overlap in cultured cells and form a hybrid 2-oxo acid dehydrogenase complex in vivo.</strong> Hum. Molec. Genet. 29: 1168-1179, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32160276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32160276</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32160276[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/10.1093/hmg/ddaa037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32160276">Leandro et al. (2020)</a> developed single and double knockouts for GCDH and DHTKD1 (<a href="/entry/614984">614984</a>) in HEK293 cells. The GCDH/DHTKD1 double knockout cells had a 2-fold decrease in glutarylcarnitine compared to GCDH knockout cells, but this level was still significantly greater than wildtype cells. <a href="#17" class="mim-tip-reference" title="Leandro, J., Dodatko, T., Aten, J., Nemeria, N. S., Zhang, X., Jordan, F., Hendrickson, R. C., Sanchez, R., Yu, C., DeVita, R. J., Houten, S. M. <strong>DHTKD1 and OGDH display substrate overlap in cultured cells and form a hybrid 2-oxo acid dehydrogenase complex in vivo.</strong> Hum. Molec. Genet. 29: 1168-1179, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32160276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32160276</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32160276[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/10.1093/hmg/ddaa037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32160276">Leandro et al. (2020)</a> then showed that the remaining glutarylcarnitine in the GCDH/DHTKD1 double knockout cells was produced via oxoglutarate dehydrogenase (OGDH; <a href="/entry/613022">613022</a>), and triple knockout cells for OGDH/GCDH/DHTKD1 had glutarylcarnitine levels that were comparable to wildtype cells. DHTKD1 was shown to physically and functionally interact with OGDH, dihydrolipoyl succinyltransferase, and dihydrolipoamide dehydrogenase to form a hybrid 2-oxoglutaric and 2-oxoadipic acid dehydrogenase complex. <a href="#17" class="mim-tip-reference" title="Leandro, J., Dodatko, T., Aten, J., Nemeria, N. S., Zhang, X., Jordan, F., Hendrickson, R. C., Sanchez, R., Yu, C., DeVita, R. J., Houten, S. M. <strong>DHTKD1 and OGDH display substrate overlap in cultured cells and form a hybrid 2-oxo acid dehydrogenase complex in vivo.</strong> Hum. Molec. Genet. 29: 1168-1179, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32160276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32160276</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32160276[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/10.1093/hmg/ddaa037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32160276">Leandro et al. (2020)</a> concluded that this relationship between DHTKD1 and OGDH limits the therapeutic potential of DHTKD1 for treatment in GA1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32160276" 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="#15" class="mim-tip-reference" title="Koeller, D. M., Woontner, M., Crnic, L. S., Kleinschmidt-DeMasters, B., Stephens, J., Hunt, E. L., Goodman, S. I. <strong>Biochemical, pathologic and behavioral analysis of a mouse model of glutaric acidemia type I.</strong> Hum. Molec. Genet. 11: 347-357, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11854167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11854167</a>] [<a href="https://doi.org/10.1093/hmg/11.4.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11854167">Koeller et al. (2002)</a> generated a mouse model of GA I by targeted deletion of the GCDH gene in embryonic stem cells. The Gcdh -/- mice had a biochemical phenotype very similar to that in patients with GA I, including comparable elevations of glutaric acid and 3-OH glutaric acid. The affected mice had a mild motor deficit but did not develop the progressive dystonia seen in patients. Pathologically, the Gcdh -/- mice had a diffuse spongiform myelinopathy similar to that seen in patients with GA I, but there was no evidence of neuron loss or astrogliosis in the striatum. Subjecting the Gcdh -/- mice to a metabolic stress failed to have any neurologic effect. <a href="#15" class="mim-tip-reference" title="Koeller, D. M., Woontner, M., Crnic, L. S., Kleinschmidt-DeMasters, B., Stephens, J., Hunt, E. L., Goodman, S. I. <strong>Biochemical, pathologic and behavioral analysis of a mouse model of glutaric acidemia type I.</strong> Hum. Molec. Genet. 11: 347-357, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11854167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11854167</a>] [<a href="https://doi.org/10.1093/hmg/11.4.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11854167">Koeller et al. (2002)</a> hypothesized that the lack of similarity in regard to the neurologic phenotype and striatal pathology of GA I patients, as compared with the Gcdh -/- mice, may be due to intrinsic differences between the striata of mice and men. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11854167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Zinnanti, W. J., Lazovic, J., Wolpert, E. B., Antonetti, D. A., Smith, M. B., Connor, J. R., Woontner, M., Goodman, S. I., Cheng, K. C. <strong>A diet-induced mouse model for glutaric aciduria type I.</strong> Brain 129: 899-910, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16446282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16446282</a>] [<a href="https://doi.org/10.1093/brain/awl009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16446282">Zinnanti et al. (2006)</a> developed a diet-induced mouse model of GA I by giving increased dietary protein and lysine to Gcdh-null mice. High protein diets were lethal to 4- and 8-week-old Gcdh-null mice within 2 to 3 and 7 to 8 days, respectively. High lysine alone resulted in vasogenic edema and blood-brain barrier breakdown within the striatum, associated with serum and tissue GA accumulation, neuronal loss, hemorrhage, paralysis, seizures and death in 75% of 4-week-old Gcdh -/- mice after 3 to 12 days. In contrast, most 8-week-old Gcdh -/- mice survived on high lysine, but developed white matter lesions, reactive astrocytes and neuronal loss after 6 weeks. <a href="#23" class="mim-tip-reference" title="Zinnanti, W. J., Lazovic, J., Wolpert, E. B., Antonetti, D. A., Smith, M. B., Connor, J. R., Woontner, M., Goodman, S. I., Cheng, K. C. <strong>A diet-induced mouse model for glutaric aciduria type I.</strong> Brain 129: 899-910, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16446282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16446282</a>] [<a href="https://doi.org/10.1093/brain/awl009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16446282">Zinnanti et al. (2006)</a> concluded that the Gcdh -/- mouse exposed to high protein or lysine is a model of human GA I, including developmentally dependent striatal vulnerability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16446282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Zinnanti, W. J., Lazovic, J., Housman, C., LaNoue, K., O'Callaghan, J. P., Simpson, I., Woontner, M., Goodman, S. I., Connor, J. R., Jacobs, R. E., Cheng, K. C. <strong>Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I.</strong> J. Clin. Invest. 117: 3258-3270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17932566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17932566</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17932566[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/10.1172/JCI31617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17932566">Zinnanti et al. (2007)</a> demonstrated that Gcdh expression was restricted to neurons in normal mouse brain. Gcdh-deficient mice showed an age-dependent susceptibility to encephalopathy, with weanling mice showing more neuronal damage than adult mice after exposure to dietary protein. Pathologic changes included vacuolated neurons and dendritic processes with enlarged mitochondria and neurofilament disorganization. Weanling Gcdh-deficient mice showed higher brain lysine and glutaric acid accumulation compared to heterozygous controls, whereas adult Gcdh-deficient mice showed no increase in these levels, consistent with decreased brain lysine uptake with maturity. Increased brain lysine and glutaric acid in weanling Gcdh-deficient mice correlated with brain injury, encephalopathy, and symptoms. The biochemical changes induced mitochondrial swelling and functional disruption. Treatment by limiting brain lysine uptake and decreasing brain lysine catabolism resulted in improved survival and decreased brain injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (NMR) spectroscopy as a diagnostic marker. The findings indicted that the age-dependent brain injury of GA I involves mitochondrial disruption precipitated by glutaric acid production from lysine in the neuronal compartment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17932566" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Gonzalez Melo, M., Remacle, N., Cudre-Cung, H.-P., Roux, C., Poms, M., Cudalbu, C., Barroso, M., Gersting, S. W., Gunther-Feichtinger, R., Mayr, J. A., Costanzo, M., Caterino, M., Ruoppolo, M., Rufenacht, V., Haberle, J., Braissant, O., Ballhausen, D. <strong>The first knock-in rat model for glutaric aciduria type I allows further insights into pathophysiology in brain and periphery.</strong> Molec. Genet. Metab. 133: 157-181, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33965309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33965309</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33965309">Gonzalez Melo et al. (2021)</a> developed a rat knock-in model of GA I that was homozygous for an R411W mutation in exon 12 of the Gcdh gene, which corresponds to the human R402W (<a href="#0004">608801.0004</a>) mutation in the GCDH gene. On a regular diet, the mutant mice did not show signs of encephalopathic crises. However, when the mutant rats were fed a high (5%) lysine diet, they exhibited lethargy, stiffness, imbalance, and spasticity. The mutant rats fed a high lysine diet also had significantly reduced food intake, resulting in decreased weight and body mass index. They demonstrated increased plasma ammonium, decreased plasma urea, and increased urine arginine, suggesting dysfunction of the urea cycle. The mutant rats on a high lysine diet were also found to have increased pipecolic acid in the plasma, urine, and striatum, suggesting upregulation of alternative mechanisms of lysine degradation. Examination of brain tissue from 6-week-old mutant rats fed a high lysine diet showed microglial activation, astrogliosis, and increased vacuolation. Free carnitine was low in the striatal tissue and urine of these mice, but not in plasma or CSF, indicating intracellular depletion of carnitine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33965309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Gonzalez Melo, M., Fontana, A. O., Viertl, D., Allenbach, G., Prior, J. O., Rotman, S., Feichtinger, R. G., Mayr, J. A., Costanzo, M., Caterino, M., Ruoppolo, M., Braissant, O., Barbey, F., Ballhausen, D. <strong>A knock-in rat model unravels acute and chronic renal toxicity in glutaric aciduria type I.</strong> Molec. Genet. Metab. 134: 287-300, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34799272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34799272</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.10.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34799272">Gonzalez Melo et al. (2021)</a> evaluated the kidney phenotype of the knock-in R411W rat model. In 6-week-old knock-in mice fed a high lysine diet, there was a decline in glomerular filtration rate and electrolyte excursions consistent with a renal tubulopathy including hypocalcemia, hypokalemia, hypophosphatemia, hypobicarbonatemia, and hyperchloremia. <a href="#5" class="mim-tip-reference" title="Gonzalez Melo, M., Fontana, A. O., Viertl, D., Allenbach, G., Prior, J. O., Rotman, S., Feichtinger, R. G., Mayr, J. A., Costanzo, M., Caterino, M., Ruoppolo, M., Braissant, O., Barbey, F., Ballhausen, D. <strong>A knock-in rat model unravels acute and chronic renal toxicity in glutaric aciduria type I.</strong> Molec. Genet. Metab. 134: 287-300, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34799272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34799272</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.10.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34799272">Gonzalez Melo et al. (2021)</a> also observed a decrease in glomerular filtration rate in 12-month-old knock-in mice fed a normal diet. Microscopic examination of the kidneys of 6-week-old knock-in mice fed a high lysine diet showed increased numbers of mitochondria, lipophilic vacuoles, and thinned apical brush border membranes in proximal tubules. In addition, enzymatic studies in kidneys of 6-week-old knock-in mice fed a high lysine diet demonstrated reduced activities of complexes I, III, and V of the respiratory chain. Proteomic studies of kidneys from the knock-in mice demonstrated dysregulation of 127 proteins associated with mitochondrial function. <a href="#5" class="mim-tip-reference" title="Gonzalez Melo, M., Fontana, A. O., Viertl, D., Allenbach, G., Prior, J. O., Rotman, S., Feichtinger, R. G., Mayr, J. A., Costanzo, M., Caterino, M., Ruoppolo, M., Braissant, O., Barbey, F., Ballhausen, D. <strong>A knock-in rat model unravels acute and chronic renal toxicity in glutaric aciduria type I.</strong> Molec. Genet. Metab. 134: 287-300, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34799272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34799272</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.10.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34799272">Gonzalez Melo et al. (2021)</a> concluded that GA I leads to acute and chronic kidney damage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34799272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>9 Selected Examples</a>):</strong>
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<a href="/allelicVariants/608801" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=608801[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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<strong>.0001 GLUTARIC ACIDEMIA I</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">rs121434366 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434366;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121434366" 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=rs121434366" 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=RCV000002162 OR RCV000724276" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002162, RCV000724276" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002162...</a>
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<p>In a patient with glutaric acidemia I (GA1; <a href="/entry/231670">231670</a>) whose parents were probably consanguineous, <a href="#2" class="mim-tip-reference" title="Biery, B. J., Goodman, S. I. <strong>Mutation in glutaryl-CoA dehydrogenase (GCDH) in glutaric acidemia type I. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A165, 1992."None>Biery and Goodman (1992)</a> demonstrated homozygosity for a T-to-C transition in the GCDH gene, resulting in a tyr195-to-his substitution. <a href="#7" class="mim-tip-reference" title="Goodman, S. I., Kratz, L. E., DiGiulio, K. A., Biery, B. J., Goodman, K. E., Isaya, G., Frerman, F. E. <strong>Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli.</strong> Hum. Molec. Genet. 4: 1493-1498, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541831</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1493" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541831">Goodman et al. (1995)</a> reported further studies of this patient and found that the mutation was actually a tyr295-to-his substitution rather than TYR195HIS. and corrected the identity of the mutation, which is tyr295-to-his (Y295H) rather than TYR195HIS. The patient was a Navajo child in whom symptoms began with chorea at the age of 4 months and whose fibroblasts were almost totally deficient in GCDH activity. The child appeared to be homozygous for the T-to-C transition at nucleotide 919 of their sequence. The mutation was not identified in control subjects or in more than 50 other GA I patients. Expression studies in E. coli showed that the mutant Y295H GCDH protein was stable but inactive. Homology modeling against the crystal structure of median-chain acyl-CoA dehydrogenase (<a href="/entry/607008">607008</a>) suggested that Y295 may lie near the adenine ring of the CoA moiety of glutaryl-CoA and interfere with substrate binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541831" 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> rs121434367 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434367;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/rs121434367?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=rs121434367" 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=rs121434367" 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=RCV000002163 OR RCV000224804" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002163, RCV000224804" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002163...</a>
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<p>In the Old Order Amish of Lancaster County, Pennsylvania, <a href="#3" class="mim-tip-reference" title="Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I. <strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong> Am. J. Hum. Genet. 59: 1006-1011, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900227</a>]" pmid="8900227">Biery et al. (1996)</a> found that the type I glutaric acidemia (GA1; <a href="/entry/231670">231670</a>) was caused in all cases by homozygosity for a 1298C-T transition in the GCDH gene, resulting in an ala421-to-val (A421V) amino acid substitution. In 4 non-Amish patients with glutaric acidemia type I, <a href="#3" class="mim-tip-reference" title="Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I. <strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong> Am. J. Hum. Genet. 59: 1006-1011, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900227</a>]" pmid="8900227">Biery et al. (1996)</a> found compound heterozygosity for mutations in the GCDH gene, with 1 allele being the A421V 'Amish' gene; all these patients had some central European ancestry. Expression studies of the A421V mutation in E. coli showed reduced enzyme activity, which the authors suggested was due to impaired association of enzyme subunits. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Strauss, K. A., Lazovic, J., Wintermark, M., Morton, D. H. <strong>Multimodal imaging of striatal degeneration in Amish patients with glutaryl-CoA dehydrogenase deficiency.</strong> Brain 130: 1905-1920, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478444</a>] [<a href="https://doi.org/10.1093/brain/awm058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17478444">Strauss et al. (2007)</a> referred to the Amish mutation as 1296C-T. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 GLUTARIC ACIDEMIA I</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">rs121434368 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434368;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121434368" 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=rs121434368" 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=RCV000002165" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002165" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002165</a>
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<p>In the course of studying Arab and non-Ashkenazi Jewish patients in Israel with glutaric acidemia I (GA1; <a href="/entry/231670">231670</a>), <a href="#1" class="mim-tip-reference" title="Anikster, Y., Shaag, A., Joseph, A., Mandel, H., Ben-Zeev, B., Christensen, E., Elpeleg, O. N. <strong>Glutaric aciduria type I in the Arab and Jewish communities in Israel.</strong> Am. J. Hum. Genet. 59: 1012-1018, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900228</a>]" pmid="8900228">Anikster et al. (1996)</a> identified a family in which at least 3 sibs were homozygous for an ACA-to-ATA transition in codon 416 of the GCDH gene, resulting in a thr416-to-ile (T416I) amino acid substitution. Remarkably, 1 of 3 homozygous sibs was asymptomatic and the asymptomatic father was also homozygous for the same mutation. The mother was a heterozygote for the T416I mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900228" 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> rs121434369 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434369;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/rs121434369?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=rs121434369" 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=rs121434369" 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=RCV000002166 OR RCV000255833 OR RCV001813936 OR RCV002512670 OR RCV003447469" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002166, RCV000255833, RCV001813936, RCV002512670, RCV003447469" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002166...</a>
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<p>In a large study of 48 European patients with glutaric acidemia I (GA1; <a href="/entry/231670">231670</a>), <a href="#24" class="mim-tip-reference" title="Zschocke, J., Quak, E., Guldberg, P., Hoffmann, G. F. <strong>Mutation analysis in glutaric aciduria type I.</strong> J. Med. Genet. 37: 177-181, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10699052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10699052</a>] [<a href="https://doi.org/10.1136/jmg.37.3.177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10699052">Zschocke et al. (2000)</a> found that the most common GCDH mutation was a 1204C-T change, resulting in an arg402-to-trp (R402W) substitution; it was present in 14 of 36 alleles (40%) in patients of German origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10699052" 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 GLUTARIC ACIDEMIA I</strong>
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GCDH, GLU365LYS
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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> rs121434370 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434370;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/rs121434370?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=rs121434370" 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=rs121434370" 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=RCV000002167 OR RCV000224528" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002167, RCV000224528" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002167...</a>
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<p><a href="#16" class="mim-tip-reference" title="Kolker, S., Ramaekers, V. T., Zschocke, J., Hoffmann, G. F. <strong>Acute encephalopathy despite early therapy in a patient with homozygosity for E365K in the glutaryl-coenzyme A dehydrogenase gene.</strong> J. Pediat. 138: 277-279, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11174631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11174631</a>] [<a href="https://doi.org/10.1067/mpd.2001.110303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11174631">Kolker et al. (2001)</a> described a patient with glutaricaciduria type I (GA1; <a href="/entry/231670">231670</a>) who was homozygous for a glu365-to-lys (E365K) substitution in the GCDH gene, a mutation previously described by <a href="#24" class="mim-tip-reference" title="Zschocke, J., Quak, E., Guldberg, P., Hoffmann, G. F. <strong>Mutation analysis in glutaric aciduria type I.</strong> J. Med. Genet. 37: 177-181, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10699052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10699052</a>] [<a href="https://doi.org/10.1136/jmg.37.3.177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10699052">Zschocke et al. (2000)</a>. This mutation is known to result in approximately 1% residual enzyme activity, causing high levels of 3-hydroxyglutaric acid and glutaric acid in plasma and urine. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10699052+11174631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0006 GLUTARIC ACIDEMIA I</strong>
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GCDH, IVS1, G-T, +5
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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> rs952356983 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs952356983;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/rs952356983?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=rs952356983" 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=rs952356983" 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=RCV000002168 OR RCV002482815" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002168, RCV002482815" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002168...</a>
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<p>In 10 patients with glutaric acidemia I (GA1; <a href="/entry/231670">231670</a>) from an inbred Aboriginal population in northern Manitoba and northwestern Ontario, <a href="#11" class="mim-tip-reference" title="Greenberg, C. R., Reimer, D., Singal, R., Triggs-Raine, B., Chudley, A. E., Dilling, L. A., Philipps, S., Haworth, J. C., Seargeant, L. E., Goodman, S. I. <strong>A G-to-T transversion at the +5 position of intron 1 in the glutaryl CoA dehydrogenase gene is associated with the Island Lake variant of glutaric acidemia type I.</strong> Hum. Molec. Genet. 4: 493-495, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795610</a>] [<a href="https://doi.org/10.1093/hmg/4.3.493" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7795610">Greenberg et al. (1995)</a> identified homozygosity for a G-to-T transversion at position +5 of IVS1 of the GCDH gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 GLUTARIC ACIDEMIA I</strong>
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GCDH, ALA293THR
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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> rs121434371 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434371;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/rs121434371?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=rs121434371" 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=rs121434371" 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=RCV000002164 OR RCV000790796" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002164, RCV000790796" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002164...</a>
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<p>In patients with glutaric acidemia I (GA1; <a href="/entry/231670">231670</a>), <a href="#3" class="mim-tip-reference" title="Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I. <strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong> Am. J. Hum. Genet. 59: 1006-1011, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900227</a>]" pmid="8900227">Biery et al. (1996)</a> identified homozygosity for a 913G-A transition in the GCDH gene, resulting in an ala293-to-thr (A293T) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0008 GLUTARIC ACIDEMIA I</strong>
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GCDH, VAL400MET
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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> rs121434372 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434372;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/rs121434372?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=rs121434372" 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=rs121434372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002169 OR RCV000224327 OR RCV002512671 OR RCV004754233" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002169, RCV000224327, RCV002512671, RCV004754233" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002169...</a>
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<p>In patients with glutaric acidemia I (GA1; <a href="/entry/231670">231670</a>), <a href="#3" class="mim-tip-reference" title="Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I. <strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong> Am. J. Hum. Genet. 59: 1006-1011, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900227</a>]" pmid="8900227">Biery et al. (1996)</a> identified homozygosity for a 1234G-A transition in the GCDH gene, resulting in a val400-to-met (V400M) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Marti-Masso, J. F., Ruiz-Martinez, J., Makarov, V., Lopez de Munain, A., Gorostidi, A., Bergareche, A., Yoon, S., Buxbaum, J. D., Paisan-Ruiz, C. <strong>Exome sequencing identifies GCDH (glutaryl-CoA dehydrogenase) mutations as a cause of a progressive form of early-onset generalized dystonia.</strong> Hum. Genet. 131: 435-442, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21912879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21912879</a>] [<a href="https://doi.org/10.1007/s00439-011-1086-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21912879">Marti-Masso et al. (2012)</a> reported 2 adult Spanish sisters with onset in infancy of a severe progressive form of dystonia affecting the upper and lower limbs, face, neck, and trunk, and resulting in severe speech impairment and the inability to walk by the teenage years. Neither had macrocephaly, organomegaly, cognitive impairment, or acute encephalopathy in childhood. Whole-exome sequence analysis identified a homozygous V400M mutation, consistent with glutaric acidemia. Laboratory studies showed decreased long-chain acylcarnitines and high excretion of 3-hydroxyglutaric acid, but urinary glutaric acid excretion was normal. Brain imaging showed increased signals in the lenticular nuclei. The findings implicated mitochondrial fatty acid metabolism as an important pathway in the development of dystonia, and <a href="#19" class="mim-tip-reference" title="Marti-Masso, J. F., Ruiz-Martinez, J., Makarov, V., Lopez de Munain, A., Gorostidi, A., Bergareche, A., Yoon, S., Buxbaum, J. D., Paisan-Ruiz, C. <strong>Exome sequencing identifies GCDH (glutaryl-CoA dehydrogenase) mutations as a cause of a progressive form of early-onset generalized dystonia.</strong> Hum. Genet. 131: 435-442, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21912879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21912879</a>] [<a href="https://doi.org/10.1007/s00439-011-1086-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21912879">Marti-Masso et al. (2012)</a> concluded that GCDH mutation analysis should be considered in the differential diagnosis of progressive forms of early-onset generalized dystonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21912879" 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>.0009 GLUTARIC ACIDEMIA I</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> rs121434373 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434373;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/rs121434373?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=rs121434373" 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=rs121434373" 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=RCV000002170 OR RCV000078256" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002170, RCV000078256" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002170...</a>
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<p>In patients with glutaric acidemia I (GA1; <a href="/entry/231670">231670</a>), <a href="#3" class="mim-tip-reference" title="Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I. <strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong> Am. J. Hum. Genet. 59: 1006-1011, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900227</a>]" pmid="8900227">Biery et al. (1996)</a> identified homozygosity for a 716G-C transversion in the GCDH gene, resulting in an arg227-to-pro (R227P) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900227" 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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<a id="1" class="mim-anchor"></a>
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<a id="Anikster1996" class="mim-anchor"></a>
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Anikster, Y., Shaag, A., Joseph, A., Mandel, H., Ben-Zeev, B., Christensen, E., Elpeleg, O. N.
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<strong>Glutaric aciduria type I in the Arab and Jewish communities in Israel.</strong>
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Am. J. Hum. Genet. 59: 1012-1018, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900228</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Biery, B. J., Goodman, S. I.
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<strong>Mutation in glutaryl-CoA dehydrogenase (GCDH) in glutaric acidemia type I. (Abstract)</strong>
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Am. J. Hum. Genet. 51 (suppl.): A165, 1992.
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Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I.
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<strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong>
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Am. J. Hum. Genet. 59: 1006-1011, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900227</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900227" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Busquets, C., Merinero, B., Christensen, E., Gelpi, J. L., Campistol, J., Pineda, M., Fernandez-Alvarez, E., Prats, J. M., Sans, A., Arteaga, R., Marti, M., Campos, J., Martinez-Pardo, M., Martinez-Bermejo, A., Ruiz-Falco, M. L., Vaquerizo, J., Orozco, M., Ugarte, M., Coll, M. J., Ribes, A.
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<strong>Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct.</strong>
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Pediat. Res. 48: 315-322, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10960496/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10960496</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10960496" 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/10.1203/00006450-200009000-00009" target="_blank">Full Text</a>]
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<a id="Gonzalez Melo2021" class="mim-anchor"></a>
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Gonzalez Melo, M., Fontana, A. O., Viertl, D., Allenbach, G., Prior, J. O., Rotman, S., Feichtinger, R. G., Mayr, J. A., Costanzo, M., Caterino, M., Ruoppolo, M., Braissant, O., Barbey, F., Ballhausen, D.
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<strong>A knock-in rat model unravels acute and chronic renal toxicity in glutaric aciduria type I.</strong>
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Molec. Genet. Metab. 134: 287-300, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34799272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34799272</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34799272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2021.10.003" target="_blank">Full Text</a>]
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Gonzalez Melo, M., Remacle, N., Cudre-Cung, H.-P., Roux, C., Poms, M., Cudalbu, C., Barroso, M., Gersting, S. W., Gunther-Feichtinger, R., Mayr, J. A., Costanzo, M., Caterino, M., Ruoppolo, M., Rufenacht, V., Haberle, J., Braissant, O., Ballhausen, D.
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<strong>The first knock-in rat model for glutaric aciduria type I allows further insights into pathophysiology in brain and periphery.</strong>
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Molec. Genet. Metab. 133: 157-181, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33965309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33965309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33965309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2021.03.017" target="_blank">Full Text</a>]
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<a id="Goodman1995" class="mim-anchor"></a>
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Goodman, S. I., Kratz, L. E., DiGiulio, K. A., Biery, B. J., Goodman, K. E., Isaya, G., Frerman, F. E.
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<strong>Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli.</strong>
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Hum. Molec. Genet. 4: 1493-1498, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/4.9.1493" target="_blank">Full Text</a>]
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<a id="Goodman1992" class="mim-anchor"></a>
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Goodman, S. I., Kratz, L. E., Frerman, F. E.
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<strong>Pork and human cDNAs encoding glutaryl-CoA dehydrogenase. In: Coates, P. M.; Tanaka, K. (eds.): New Developments in Fatty Acid Oxidation.</strong>
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New York: Wiley-Liss 1992. Pp. 169-173.
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Goodman, S. I., Stein, D. E., Schlesinger, S., Christensen, E., Schwartz, M., Greenberg, C. R., Elpeleg, O. N.
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<strong>Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations.</strong>
|
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Hum. Mutat. 12: 141-144, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9711871/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9711871</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9711871" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)12:3<141::AID-HUMU1>3.0.CO;2-K" target="_blank">Full Text</a>]
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Greenberg, C. R., Duncan, A. M. V., Gregory, C. A., Singal, R., Goodman, S. I.
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<strong>Assignment of human glutaryl-CoA dehydrogenase gene (GCDH) to the short arm of chromosome 19 (19p13.2) by in situ hybridization and somatic cell hybrid analysis.</strong>
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Genomics 21: 289-290, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8088809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8088809</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8088809" 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.1994.1264" target="_blank">Full Text</a>]
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<a id="Greenberg1995" class="mim-anchor"></a>
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Greenberg, C. R., Reimer, D., Singal, R., Triggs-Raine, B., Chudley, A. E., Dilling, L. A., Philipps, S., Haworth, J. C., Seargeant, L. E., Goodman, S. I.
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<strong>A G-to-T transversion at the +5 position of intron 1 in the glutaryl CoA dehydrogenase gene is associated with the Island Lake variant of glutaric acidemia type I.</strong>
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Hum. Molec. Genet. 4: 493-495, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795610</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
|
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|
|
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|
|
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|
|
Gurbuz, B. B., Yilmaz, D. Y., Coskun, T., Tokath, A., Dursun, A., Sivri, H. S.
|
|
<strong>Glutaric aciduria type 1: genetic and phenotypic spectrum in 53 patients.</strong>
|
|
Europ. J. Med. Genet. 63: 104032, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32777384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32777384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32777384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ejmg.2020.104032" target="_blank">Full Text</a>]
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|
|
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|
|
|
|
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|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Keyser2008" class="mim-anchor"></a>
|
|
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|
|
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|
|
Keyser, B., Muhlhausen, C., Dickmanns, A., Christensen, E., Muschol, N., Ullrich, K., Braulke, T.
|
|
<strong>Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH).</strong>
|
|
Hum. Molec. Genet. 17: 3854-3863, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18775954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18775954</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18775954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
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|
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[<a href="https://doi.org/10.1093/hmg/ddn284" target="_blank">Full Text</a>]
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Koeller1995" class="mim-anchor"></a>
|
|
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|
|
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|
|
Koeller, D. M., DiGiulio, K. A., Angeloni, S. V., Dowler, L. L., Frerman, F. E., White, R. A., Goodman, S. I.
|
|
<strong>Cloning, structure, and chromosome localization of the mouse glutaryl-CoA dehydrogenase gene.</strong>
|
|
Genomics 28: 508-512, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7490088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7490088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7490088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1995.1182" target="_blank">Full Text</a>]
|
|
|
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|
|
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|
|
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|
|
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|
|
|
|
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|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Koeller2002" class="mim-anchor"></a>
|
|
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|
|
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|
|
Koeller, D. M., Woontner, M., Crnic, L. S., Kleinschmidt-DeMasters, B., Stephens, J., Hunt, E. L., Goodman, S. I.
|
|
<strong>Biochemical, pathologic and behavioral analysis of a mouse model of glutaric acidemia type I.</strong>
|
|
Hum. Molec. Genet. 11: 347-357, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11854167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11854167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11854167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/11.4.347" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Kolker2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kolker, S., Ramaekers, V. T., Zschocke, J., Hoffmann, G. F.
|
|
<strong>Acute encephalopathy despite early therapy in a patient with homozygosity for E365K in the glutaryl-coenzyme A dehydrogenase gene.</strong>
|
|
J. Pediat. 138: 277-279, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11174631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11174631</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11174631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
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|
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[<a href="https://doi.org/10.1067/mpd.2001.110303" target="_blank">Full Text</a>]
|
|
|
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|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
|
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|
|
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|
|
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|
|
Leandro, J., Dodatko, T., Aten, J., Nemeria, N. S., Zhang, X., Jordan, F., Hendrickson, R. C., Sanchez, R., Yu, C., DeVita, R. J., Houten, S. M.
|
|
<strong>DHTKD1 and OGDH display substrate overlap in cultured cells and form a hybrid 2-oxo acid dehydrogenase complex in vivo.</strong>
|
|
Hum. Molec. Genet. 29: 1168-1179, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32160276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32160276</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32160276[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=32160276" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1093/hmg/ddaa037" target="_blank">Full Text</a>]
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|
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|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
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|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lenich, A. C., Goodman, S. I.
|
|
<strong>The purification and characterization of glutaryl-coenzyme A dehydrogenase from porcine and human liver.</strong>
|
|
J. Biol. Chem. 261: 4090-4096, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3081514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3081514</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3081514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
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|
|
|
|
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|
|
<a id="19" class="mim-anchor"></a>
|
|
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|
|
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|
|
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|
|
Marti-Masso, J. F., Ruiz-Martinez, J., Makarov, V., Lopez de Munain, A., Gorostidi, A., Bergareche, A., Yoon, S., Buxbaum, J. D., Paisan-Ruiz, C.
|
|
<strong>Exome sequencing identifies GCDH (glutaryl-CoA dehydrogenase) mutations as a cause of a progressive form of early-onset generalized dystonia.</strong>
|
|
Hum. Genet. 131: 435-442, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21912879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21912879</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21912879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1007/s00439-011-1086-6" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
|
<a id="20" class="mim-anchor"></a>
|
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|
|
<div class="">
|
|
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|
|
Schwartz, M., Christensen, E., Superti-Furga, A., Brandt, N. J.
|
|
<strong>The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and 13 novel mutations causing glutaric aciduria type I.</strong>
|
|
Hum. Genet. 102: 452-458, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600243</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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[<a href="https://doi.org/10.1007/s004390050720" target="_blank">Full Text</a>]
|
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|
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|
|
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|
|
|
|
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|
|
<a id="21" class="mim-anchor"></a>
|
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|
|
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|
|
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|
|
Strauss, K. A., Lazovic, J., Wintermark, M., Morton, D. H.
|
|
<strong>Multimodal imaging of striatal degeneration in Amish patients with glutaryl-CoA dehydrogenase deficiency.</strong>
|
|
Brain 130: 1905-1920, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478444</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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|
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[<a href="https://doi.org/10.1093/brain/awm058" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
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|
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|
|
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|
|
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|
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Zinnanti, W. J., Lazovic, J., Housman, C., LaNoue, K., O'Callaghan, J. P., Simpson, I., Woontner, M., Goodman, S. I., Connor, J. R., Jacobs, R. E., Cheng, K. C.
|
|
<strong>Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I.</strong>
|
|
J. Clin. Invest. 117: 3258-3270, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17932566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17932566</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17932566[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=17932566" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI31617" target="_blank">Full Text</a>]
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|
|
<strong>A diet-induced mouse model for glutaric aciduria type I.</strong>
|
|
Brain 129: 899-910, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16446282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16446282</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16446282" 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/awl009" target="_blank">Full Text</a>]
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|
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Zschocke, J., Quak, E., Guldberg, P., Hoffmann, G. F.
|
|
<strong>Mutation analysis in glutaric aciduria type I.</strong>
|
|
J. Med. Genet. 37: 177-181, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10699052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10699052</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10699052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.37.3.177" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 02/17/2022
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Hilary J. Vernon - updated : 01/07/2022<br>Hilary J. Vernon - updated : 12/22/2021<br>Hilary J. Vernon - updated : 08/11/2021<br>Cassandra L. Kniffin - updated : 3/26/2012<br>Cassandra L. Kniffin - updated : 3/30/2011<br>Cassandra L. Kniffin - updated : 12/17/2007<br>Victor A. McKusick - updated : 8/8/2007
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Cassandra L. Kniffin : 7/15/2004
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carol : 01/10/2022<br>carol : 01/07/2022<br>carol : 12/22/2021<br>carol : 08/11/2021<br>carol : 08/09/2017<br>alopez : 10/04/2016<br>carol : 07/18/2016<br>alopez : 4/2/2012<br>ckniffin : 3/26/2012<br>wwang : 4/11/2011<br>ckniffin : 3/30/2011<br>wwang : 2/18/2008<br>ckniffin : 12/17/2007<br>alopez : 8/27/2007<br>terry : 8/8/2007<br>terry : 4/7/2005<br>carol : 7/22/2004<br>ckniffin : 7/16/2004
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<h3>
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<span class="mim-font">
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<strong>*</strong> 608801
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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GLUTARYL-CoA DEHYDROGENASE; GCDH
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</h3>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GCDH</em></strong>
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</span>
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</p>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 360416003;
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<strong>ICD10CM:</strong> E72.3;
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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: 19p13.13
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Genomic coordinates <span class="small">(GRCh38)</span> : 19:12,891,129-12,899,999 </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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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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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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Inheritance
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<th>
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Phenotype <br /> mapping key
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</thead>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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19p13.13
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</td>
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<td>
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<span class="mim-font">
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Glutaricaciduria, type I
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</td>
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<span class="mim-font">
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231670
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<td>
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<span class="mim-font">
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Autosomal recessive
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</td>
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<td>
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<span class="mim-font">
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3
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</tr>
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</tbody>
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</table>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</h4>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Glutaryl-CoA dehydrogenase (GCDH; EC 1.3.8.6) is an acyl dehydrogenase involved in the metabolism of lysine, hydroxylysine, and tryptophan. Specifically, it is responsible for the dehydrogenation and decarboxylation of glutaryl-CoA to crotonyl-CoA in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. The active enzyme exists as a homotetramer in the mitochondrial matrix.</p>
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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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</h4>
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</div>
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<span class="mim-text-font">
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<p>Lenich and Goodman (1986) purified the glutaryl-CoA dehydrogenase protein from porcine and human liver mitochondria. Goodman et al. (1992) and Goodman et al. (1995) cloned and sequenced a human GCDH cDNA. Goodman et al. (1995) found that the cDNA encodes a 438-amino acid precursor protein and a 394-amino acid mature protein with a molecular mass of 43.3 kD. The protein shares 92% sequence identity with its porcine homolog. Alternative splicing between exons 10 and 11 produces 2 GCDH mRNA transcripts, only 1 of which is enzymatically active. The precursor protein undergoes 1-step cleavage by mitochondrial processing peptidase to form the mature GCDH subunit. </p><p>Koeller et al. (1995) showed that the mouse Gcdh cDNA encodes a predicted protein of 438 amino acids which is highly conserved with respect to the pig and human sequences. </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Biery et al. (1996) determined that GCDH gene contains 11 exons and spans approximately 7 kb. Schwartz et al. (1998) reported the sequence of introns 1-3 and 6-9 of the GCDH gene, as well as parts of introns 4, 5, and 10. </p><p>Koeller et al. (1995) determined that the mouse gene contains 11 exons and spans about 7 kb of genomic DNA. </p>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By in situ hybridization and somatic cell hybrid analysis, Greenberg et al. (1994) mapped the GCDH gene to chromosome 19p13.2. </p><p>Using interspecific backcross mapping, Koeller et al. (1995) mapped the mouse gene to chromosome 8 within a region that has homology of synteny to human chromosome 19. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</h4>
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<span class="mim-text-font">
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<p>In a Navajo child with glutaric acidemia type I (GA1; 231670), Biery and Goodman (1992) and Goodman et al. (1995) identified homozygosity for a mutation in the GCDH gene (608801.0001). </p><p>Among 64 unrelated patients with glutaric acidemia type I, Biery et al. (1996) identified 12 mutations and several polymorphisms in 7 exons of the GCDH gene (see, e.g., 608801.0007-608801.0009). Several mutations were found in more than one patient, but no one prevalent mutation was detected in the general population. However, a single mutation was found as the cause of glutaric acidemia in the Old Order Amish of Lancaster County, Pennsylvania (A421V; 608801.0002). Biery et al. (1996) expressed several mutations in Escherichia coli; all produced diminished enzyme activity. </p><p>Among 8 families with glutaric acidemia I diagnosed in Israel, 6 of Muslim origin and 2 of non-Ashkenazi Jewish background, Anikster et al. (1996) identified 7 mutations in the GCDH gene (see, e.g., 608801.0003). The molecular basis for the clinical variability in GA I families was not revealed by these findings. Anikster et al. (1996) stated that the occurrence of multiple novel alleles in a small geographic area was explained by their recent origin in isolated communities with a high consanguinity rate. In 5 of the families included in this study, the diagnosis of GA I in the index case was followed by identification of another affected sib, who was either asymptomatic, suffered from a milder form of the disease, or was misdiagnosed for a nonmetabolic condition. </p><p>Schwartz et al. (1998) reported 21 different mutations in the GCDH gene found in a total of 20 patients with glutaric acidemia type I. These mutations accounted for 38 of 40 mutant alleles in this population. </p><p>Goodman et al. (1998) reviewed 63 mutations in the GCDH gene that had been identified by several laboratories as the cause of glutaric acidemia I, 30 of them for the first time. They also reported data on expression in E. coli and the relationship to the clinical and biochemical phenotype. No common GCDH mutation was found, and little if any relationship between genotype and clinical phenotype could be recognized. The mutations were widely distributed through the gene, with the largest number in exon 10. </p><p>Zschocke et al. (2000) reported a denaturing gradient gel electrophoresis (DGGE) method for detection of mutations in the GCDH gene. Using this method, they found mutations in both alleles in 48 individuals with confirmed GCDH deficiency. No mutations were found in individuals with clinical suspicion of GCDH deficiency but normal enzyme levels. They identified a total of 38 different mutations; 27 were found in single patients, and 21 mutations were previously unreported. Fourteen mutations involved CpG sites. R402W (608801.0004) was the most common mutation in Europeans, accounting for 40% of alleles in patients of German origin. Zschocke et al. (2000) concluded that the high sensitivity of this method allowed for rapid and cost-efficient diagnosis of glutaricaciduria type I in instances where enzyme analyses are not available or feasible. </p><p>Busquets et al. (2000) identified 13 novel and 10 known GCDH mutations in a population of 43 Spanish patients with GA I representing 2 genetically and biochemically distinct groups. Mutations A293T (608801.0007) and R402W (608801.0004) were common (30% and 28%, respectively) in 23 patients with typical biochemical findings, whereas mutations V400M (608801.0008) and R227P (608801.0009) (combined frequency of 53%) were only found in the 17 patients with normal glutarate and mild elevation of 3-hydroxyglutarate by urine organic acid analysis. The severity of the clinical phenotype appeared to correlate with encephalopathic crises, but not with residual enzyme activity or genotype. </p><p>By GCDH activity assay in transfected baby hamster kidney cells, Keyser et al. (2008) found that expression of GCDH mutants R138G, R402W (608801.0004), and E414K resulted in a complete lack of enzymatic activity. The M264V mutant had 10% residual activity, and Western blot and pulse-chase analysis indicated that the M263V mutant protein was subject to rapid intramitochondrial degradation. The M263V and R402W mutants showed defective homotetrameric assembly. Molecular modeling of mutant GCDH showed that arg138 and glu414 are both located at the bottom of the active site and required for proper arrangement of the ligand, and that the met263 residue on the surface of the protein might be part of the contact interface to interacting proteins. </p><p>By direct sequencing of the GCDH gene in 53 Turkish patients with GA1 from 39 unrelated families, Gurbuz et al. (2020) identified mutations in 46 patients, 40 of whom had homozygous mutations. About 85% of the patients were from consanguineous families. Twenty different mutations, 7 of which were novel, were identified, including 17 missense, 2 deletions, and 1 nonsense. The most common mutations were R402W (608801.0004), P248L, and L340F, with a frequency of 21.2%, 18.2%, and 12.1%, respectively. </p><p>Using CRISPR editing, Leandro et al. (2020) developed single and double knockouts for GCDH and DHTKD1 (614984) in HEK293 cells. The GCDH/DHTKD1 double knockout cells had a 2-fold decrease in glutarylcarnitine compared to GCDH knockout cells, but this level was still significantly greater than wildtype cells. Leandro et al. (2020) then showed that the remaining glutarylcarnitine in the GCDH/DHTKD1 double knockout cells was produced via oxoglutarate dehydrogenase (OGDH; 613022), and triple knockout cells for OGDH/GCDH/DHTKD1 had glutarylcarnitine levels that were comparable to wildtype cells. DHTKD1 was shown to physically and functionally interact with OGDH, dihydrolipoyl succinyltransferase, and dihydrolipoamide dehydrogenase to form a hybrid 2-oxoglutaric and 2-oxoadipic acid dehydrogenase complex. Leandro et al. (2020) concluded that this relationship between DHTKD1 and OGDH limits the therapeutic potential of DHTKD1 for treatment in GA1. </p>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</h4>
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<span class="mim-text-font">
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<p>Koeller et al. (2002) generated a mouse model of GA I by targeted deletion of the GCDH gene in embryonic stem cells. The Gcdh -/- mice had a biochemical phenotype very similar to that in patients with GA I, including comparable elevations of glutaric acid and 3-OH glutaric acid. The affected mice had a mild motor deficit but did not develop the progressive dystonia seen in patients. Pathologically, the Gcdh -/- mice had a diffuse spongiform myelinopathy similar to that seen in patients with GA I, but there was no evidence of neuron loss or astrogliosis in the striatum. Subjecting the Gcdh -/- mice to a metabolic stress failed to have any neurologic effect. Koeller et al. (2002) hypothesized that the lack of similarity in regard to the neurologic phenotype and striatal pathology of GA I patients, as compared with the Gcdh -/- mice, may be due to intrinsic differences between the striata of mice and men. </p><p>Zinnanti et al. (2006) developed a diet-induced mouse model of GA I by giving increased dietary protein and lysine to Gcdh-null mice. High protein diets were lethal to 4- and 8-week-old Gcdh-null mice within 2 to 3 and 7 to 8 days, respectively. High lysine alone resulted in vasogenic edema and blood-brain barrier breakdown within the striatum, associated with serum and tissue GA accumulation, neuronal loss, hemorrhage, paralysis, seizures and death in 75% of 4-week-old Gcdh -/- mice after 3 to 12 days. In contrast, most 8-week-old Gcdh -/- mice survived on high lysine, but developed white matter lesions, reactive astrocytes and neuronal loss after 6 weeks. Zinnanti et al. (2006) concluded that the Gcdh -/- mouse exposed to high protein or lysine is a model of human GA I, including developmentally dependent striatal vulnerability. </p><p>Zinnanti et al. (2007) demonstrated that Gcdh expression was restricted to neurons in normal mouse brain. Gcdh-deficient mice showed an age-dependent susceptibility to encephalopathy, with weanling mice showing more neuronal damage than adult mice after exposure to dietary protein. Pathologic changes included vacuolated neurons and dendritic processes with enlarged mitochondria and neurofilament disorganization. Weanling Gcdh-deficient mice showed higher brain lysine and glutaric acid accumulation compared to heterozygous controls, whereas adult Gcdh-deficient mice showed no increase in these levels, consistent with decreased brain lysine uptake with maturity. Increased brain lysine and glutaric acid in weanling Gcdh-deficient mice correlated with brain injury, encephalopathy, and symptoms. The biochemical changes induced mitochondrial swelling and functional disruption. Treatment by limiting brain lysine uptake and decreasing brain lysine catabolism resulted in improved survival and decreased brain injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (NMR) spectroscopy as a diagnostic marker. The findings indicted that the age-dependent brain injury of GA I involves mitochondrial disruption precipitated by glutaric acid production from lysine in the neuronal compartment. </p><p>Gonzalez Melo et al. (2021) developed a rat knock-in model of GA I that was homozygous for an R411W mutation in exon 12 of the Gcdh gene, which corresponds to the human R402W (608801.0004) mutation in the GCDH gene. On a regular diet, the mutant mice did not show signs of encephalopathic crises. However, when the mutant rats were fed a high (5%) lysine diet, they exhibited lethargy, stiffness, imbalance, and spasticity. The mutant rats fed a high lysine diet also had significantly reduced food intake, resulting in decreased weight and body mass index. They demonstrated increased plasma ammonium, decreased plasma urea, and increased urine arginine, suggesting dysfunction of the urea cycle. The mutant rats on a high lysine diet were also found to have increased pipecolic acid in the plasma, urine, and striatum, suggesting upregulation of alternative mechanisms of lysine degradation. Examination of brain tissue from 6-week-old mutant rats fed a high lysine diet showed microglial activation, astrogliosis, and increased vacuolation. Free carnitine was low in the striatal tissue and urine of these mice, but not in plasma or CSF, indicating intracellular depletion of carnitine. </p><p>Gonzalez Melo et al. (2021) evaluated the kidney phenotype of the knock-in R411W rat model. In 6-week-old knock-in mice fed a high lysine diet, there was a decline in glomerular filtration rate and electrolyte excursions consistent with a renal tubulopathy including hypocalcemia, hypokalemia, hypophosphatemia, hypobicarbonatemia, and hyperchloremia. Gonzalez Melo et al. (2021) also observed a decrease in glomerular filtration rate in 12-month-old knock-in mice fed a normal diet. Microscopic examination of the kidneys of 6-week-old knock-in mice fed a high lysine diet showed increased numbers of mitochondria, lipophilic vacuoles, and thinned apical brush border membranes in proximal tubules. In addition, enzymatic studies in kidneys of 6-week-old knock-in mice fed a high lysine diet demonstrated reduced activities of complexes I, III, and V of the respiratory chain. Proteomic studies of kidneys from the knock-in mice demonstrated dysregulation of 127 proteins associated with mitochondrial function. Gonzalez Melo et al. (2021) concluded that GA I leads to acute and chronic kidney damage. </p>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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<h4>
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<span class="mim-font">
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<strong>.0001 GLUTARIC ACIDEMIA I</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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GCDH, TYR295HIS
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<br />
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SNP: rs121434366,
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ClinVar: RCV000002162, RCV000724276
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<span class="mim-text-font">
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<p>In a patient with glutaric acidemia I (GA1; 231670) whose parents were probably consanguineous, Biery and Goodman (1992) demonstrated homozygosity for a T-to-C transition in the GCDH gene, resulting in a tyr195-to-his substitution. Goodman et al. (1995) reported further studies of this patient and found that the mutation was actually a tyr295-to-his substitution rather than TYR195HIS. and corrected the identity of the mutation, which is tyr295-to-his (Y295H) rather than TYR195HIS. The patient was a Navajo child in whom symptoms began with chorea at the age of 4 months and whose fibroblasts were almost totally deficient in GCDH activity. The child appeared to be homozygous for the T-to-C transition at nucleotide 919 of their sequence. The mutation was not identified in control subjects or in more than 50 other GA I patients. Expression studies in E. coli showed that the mutant Y295H GCDH protein was stable but inactive. Homology modeling against the crystal structure of median-chain acyl-CoA dehydrogenase (607008) suggested that Y295 may lie near the adenine ring of the CoA moiety of glutaryl-CoA and interfere with substrate binding. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 GLUTARIC ACIDEMIA I</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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GCDH, ALA421VAL
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<br />
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SNP: rs121434367,
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gnomAD: rs121434367,
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ClinVar: RCV000002163, RCV000224804
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</span>
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<div>
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<span class="mim-text-font">
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<p>In the Old Order Amish of Lancaster County, Pennsylvania, Biery et al. (1996) found that the type I glutaric acidemia (GA1; 231670) was caused in all cases by homozygosity for a 1298C-T transition in the GCDH gene, resulting in an ala421-to-val (A421V) amino acid substitution. In 4 non-Amish patients with glutaric acidemia type I, Biery et al. (1996) found compound heterozygosity for mutations in the GCDH gene, with 1 allele being the A421V 'Amish' gene; all these patients had some central European ancestry. Expression studies of the A421V mutation in E. coli showed reduced enzyme activity, which the authors suggested was due to impaired association of enzyme subunits. </p><p>Strauss et al. (2007) referred to the Amish mutation as 1296C-T. </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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<strong>.0003 GLUTARIC ACIDEMIA I</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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GCDH, THR416ILE
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<br />
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SNP: rs121434368,
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ClinVar: RCV000002165
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In the course of studying Arab and non-Ashkenazi Jewish patients in Israel with glutaric acidemia I (GA1; 231670), Anikster et al. (1996) identified a family in which at least 3 sibs were homozygous for an ACA-to-ATA transition in codon 416 of the GCDH gene, resulting in a thr416-to-ile (T416I) amino acid substitution. Remarkably, 1 of 3 homozygous sibs was asymptomatic and the asymptomatic father was also homozygous for the same mutation. The mother was a heterozygote for the T416I mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0004 GLUTARIC ACIDEMIA I</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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GCDH, ARG402TRP
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<br />
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SNP: rs121434369,
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gnomAD: rs121434369,
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ClinVar: RCV000002166, RCV000255833, RCV001813936, RCV002512670, RCV003447469
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a large study of 48 European patients with glutaric acidemia I (GA1; 231670), Zschocke et al. (2000) found that the most common GCDH mutation was a 1204C-T change, resulting in an arg402-to-trp (R402W) substitution; it was present in 14 of 36 alleles (40%) in patients of German origin. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0005 GLUTARIC ACIDEMIA I</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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GCDH, GLU365LYS
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<br />
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SNP: rs121434370,
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gnomAD: rs121434370,
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ClinVar: RCV000002167, RCV000224528
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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>Kolker et al. (2001) described a patient with glutaricaciduria type I (GA1; 231670) who was homozygous for a glu365-to-lys (E365K) substitution in the GCDH gene, a mutation previously described by Zschocke et al. (2000). This mutation is known to result in approximately 1% residual enzyme activity, causing high levels of 3-hydroxyglutaric acid and glutaric acid in plasma and urine. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0006 GLUTARIC ACIDEMIA I</strong>
|
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</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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GCDH, IVS1, G-T, +5
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<br />
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SNP: rs952356983,
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gnomAD: rs952356983,
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ClinVar: RCV000002168, RCV002482815
|
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 10 patients with glutaric acidemia I (GA1; 231670) from an inbred Aboriginal population in northern Manitoba and northwestern Ontario, Greenberg et al. (1995) identified homozygosity for a G-to-T transversion at position +5 of IVS1 of the GCDH gene. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 GLUTARIC ACIDEMIA I</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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GCDH, ALA293THR
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<br />
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SNP: rs121434371,
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|
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gnomAD: rs121434371,
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|
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ClinVar: RCV000002164, RCV000790796
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with glutaric acidemia I (GA1; 231670), Biery et al. (1996) identified homozygosity for a 913G-A transition in the GCDH gene, resulting in an ala293-to-thr (A293T) substitution. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 GLUTARIC ACIDEMIA I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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GCDH, VAL400MET
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<br />
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SNP: rs121434372,
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gnomAD: rs121434372,
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|
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ClinVar: RCV000002169, RCV000224327, RCV002512671, RCV004754233
|
|
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|
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</span>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with glutaric acidemia I (GA1; 231670), Biery et al. (1996) identified homozygosity for a 1234G-A transition in the GCDH gene, resulting in a val400-to-met (V400M) substitution. </p><p>Marti-Masso et al. (2012) reported 2 adult Spanish sisters with onset in infancy of a severe progressive form of dystonia affecting the upper and lower limbs, face, neck, and trunk, and resulting in severe speech impairment and the inability to walk by the teenage years. Neither had macrocephaly, organomegaly, cognitive impairment, or acute encephalopathy in childhood. Whole-exome sequence analysis identified a homozygous V400M mutation, consistent with glutaric acidemia. Laboratory studies showed decreased long-chain acylcarnitines and high excretion of 3-hydroxyglutaric acid, but urinary glutaric acid excretion was normal. Brain imaging showed increased signals in the lenticular nuclei. The findings implicated mitochondrial fatty acid metabolism as an important pathway in the development of dystonia, and Marti-Masso et al. (2012) concluded that GCDH mutation analysis should be considered in the differential diagnosis of progressive forms of early-onset generalized dystonia. </p>
|
|
</span>
|
|
</div>
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|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 GLUTARIC ACIDEMIA I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
GCDH, ARG227PRO
|
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|
|
|
<br />
|
|
|
|
SNP: rs121434373,
|
|
|
|
|
|
gnomAD: rs121434373,
|
|
|
|
|
|
ClinVar: RCV000002170, RCV000078256
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with glutaric acidemia I (GA1; 231670), Biery et al. (1996) identified homozygosity for a 716G-C transversion in the GCDH gene, resulting in an arg227-to-pro (R227P) substitution. </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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</div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Anikster, Y., Shaag, A., Joseph, A., Mandel, H., Ben-Zeev, B., Christensen, E., Elpeleg, O. N.
|
|
<strong>Glutaric aciduria type I in the Arab and Jewish communities in Israel.</strong>
|
|
Am. J. Hum. Genet. 59: 1012-1018, 1996.
|
|
|
|
|
|
[PubMed: 8900228]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Biery, B. J., Goodman, S. I.
|
|
<strong>Mutation in glutaryl-CoA dehydrogenase (GCDH) in glutaric acidemia type I. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A165, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Biery, B. J., Stein, D. E., Morton, D. H., Goodman, S. I.
|
|
<strong>Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.</strong>
|
|
Am. J. Hum. Genet. 59: 1006-1011, 1996.
|
|
|
|
|
|
[PubMed: 8900227]
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|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Busquets, C., Merinero, B., Christensen, E., Gelpi, J. L., Campistol, J., Pineda, M., Fernandez-Alvarez, E., Prats, J. M., Sans, A., Arteaga, R., Marti, M., Campos, J., Martinez-Pardo, M., Martinez-Bermejo, A., Ruiz-Falco, M. L., Vaquerizo, J., Orozco, M., Ugarte, M., Coll, M. J., Ribes, A.
|
|
<strong>Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct.</strong>
|
|
Pediat. Res. 48: 315-322, 2000.
|
|
|
|
|
|
[PubMed: 10960496]
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|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-200009000-00009]
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gonzalez Melo, M., Fontana, A. O., Viertl, D., Allenbach, G., Prior, J. O., Rotman, S., Feichtinger, R. G., Mayr, J. A., Costanzo, M., Caterino, M., Ruoppolo, M., Braissant, O., Barbey, F., Ballhausen, D.
|
|
<strong>A knock-in rat model unravels acute and chronic renal toxicity in glutaric aciduria type I.</strong>
|
|
Molec. Genet. Metab. 134: 287-300, 2021.
|
|
|
|
|
|
[PubMed: 34799272]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2021.10.003]
|
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gonzalez Melo, M., Remacle, N., Cudre-Cung, H.-P., Roux, C., Poms, M., Cudalbu, C., Barroso, M., Gersting, S. W., Gunther-Feichtinger, R., Mayr, J. A., Costanzo, M., Caterino, M., Ruoppolo, M., Rufenacht, V., Haberle, J., Braissant, O., Ballhausen, D.
|
|
<strong>The first knock-in rat model for glutaric aciduria type I allows further insights into pathophysiology in brain and periphery.</strong>
|
|
Molec. Genet. Metab. 133: 157-181, 2021.
|
|
|
|
|
|
[PubMed: 33965309]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2021.03.017]
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</p>
|
|
</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Goodman, S. I., Kratz, L. E., DiGiulio, K. A., Biery, B. J., Goodman, K. E., Isaya, G., Frerman, F. E.
|
|
<strong>Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli.</strong>
|
|
Hum. Molec. Genet. 4: 1493-1498, 1995.
|
|
|
|
|
|
[PubMed: 8541831]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.9.1493]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goodman, S. I., Kratz, L. E., Frerman, F. E.
|
|
<strong>Pork and human cDNAs encoding glutaryl-CoA dehydrogenase. In: Coates, P. M.; Tanaka, K. (eds.): New Developments in Fatty Acid Oxidation.</strong>
|
|
New York: Wiley-Liss 1992. Pp. 169-173.
|
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|
|
</p>
|
|
</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Goodman, S. I., Stein, D. E., Schlesinger, S., Christensen, E., Schwartz, M., Greenberg, C. R., Elpeleg, O. N.
|
|
<strong>Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations.</strong>
|
|
Hum. Mutat. 12: 141-144, 1998.
|
|
|
|
|
|
[PubMed: 9711871]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)12:3<141::AID-HUMU1>3.0.CO;2-K]
|
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|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Greenberg, C. R., Duncan, A. M. V., Gregory, C. A., Singal, R., Goodman, S. I.
|
|
<strong>Assignment of human glutaryl-CoA dehydrogenase gene (GCDH) to the short arm of chromosome 19 (19p13.2) by in situ hybridization and somatic cell hybrid analysis.</strong>
|
|
Genomics 21: 289-290, 1994.
|
|
|
|
|
|
[PubMed: 8088809]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1264]
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|
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Greenberg, C. R., Reimer, D., Singal, R., Triggs-Raine, B., Chudley, A. E., Dilling, L. A., Philipps, S., Haworth, J. C., Seargeant, L. E., Goodman, S. I.
|
|
<strong>A G-to-T transversion at the +5 position of intron 1 in the glutaryl CoA dehydrogenase gene is associated with the Island Lake variant of glutaric acidemia type I.</strong>
|
|
Hum. Molec. Genet. 4: 493-495, 1995.
|
|
|
|
|
|
[PubMed: 7795610]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.3.493]
|
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gurbuz, B. B., Yilmaz, D. Y., Coskun, T., Tokath, A., Dursun, A., Sivri, H. S.
|
|
<strong>Glutaric aciduria type 1: genetic and phenotypic spectrum in 53 patients.</strong>
|
|
Europ. J. Med. Genet. 63: 104032, 2020.
|
|
|
|
|
|
[PubMed: 32777384]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ejmg.2020.104032]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Keyser, B., Muhlhausen, C., Dickmanns, A., Christensen, E., Muschol, N., Ullrich, K., Braulke, T.
|
|
<strong>Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH).</strong>
|
|
Hum. Molec. Genet. 17: 3854-3863, 2008.
|
|
|
|
|
|
[PubMed: 18775954]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn284]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koeller, D. M., DiGiulio, K. A., Angeloni, S. V., Dowler, L. L., Frerman, F. E., White, R. A., Goodman, S. I.
|
|
<strong>Cloning, structure, and chromosome localization of the mouse glutaryl-CoA dehydrogenase gene.</strong>
|
|
Genomics 28: 508-512, 1995.
|
|
|
|
|
|
[PubMed: 7490088]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1995.1182]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koeller, D. M., Woontner, M., Crnic, L. S., Kleinschmidt-DeMasters, B., Stephens, J., Hunt, E. L., Goodman, S. I.
|
|
<strong>Biochemical, pathologic and behavioral analysis of a mouse model of glutaric acidemia type I.</strong>
|
|
Hum. Molec. Genet. 11: 347-357, 2002.
|
|
|
|
|
|
[PubMed: 11854167]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/11.4.347]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kolker, S., Ramaekers, V. T., Zschocke, J., Hoffmann, G. F.
|
|
<strong>Acute encephalopathy despite early therapy in a patient with homozygosity for E365K in the glutaryl-coenzyme A dehydrogenase gene.</strong>
|
|
J. Pediat. 138: 277-279, 2001.
|
|
|
|
|
|
[PubMed: 11174631]
|
|
|
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|
[Full Text: https://doi.org/10.1067/mpd.2001.110303]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leandro, J., Dodatko, T., Aten, J., Nemeria, N. S., Zhang, X., Jordan, F., Hendrickson, R. C., Sanchez, R., Yu, C., DeVita, R. J., Houten, S. M.
|
|
<strong>DHTKD1 and OGDH display substrate overlap in cultured cells and form a hybrid 2-oxo acid dehydrogenase complex in vivo.</strong>
|
|
Hum. Molec. Genet. 29: 1168-1179, 2020.
|
|
|
|
|
|
[PubMed: 32160276]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddaa037]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lenich, A. C., Goodman, S. I.
|
|
<strong>The purification and characterization of glutaryl-coenzyme A dehydrogenase from porcine and human liver.</strong>
|
|
J. Biol. Chem. 261: 4090-4096, 1986.
|
|
|
|
|
|
[PubMed: 3081514]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marti-Masso, J. F., Ruiz-Martinez, J., Makarov, V., Lopez de Munain, A., Gorostidi, A., Bergareche, A., Yoon, S., Buxbaum, J. D., Paisan-Ruiz, C.
|
|
<strong>Exome sequencing identifies GCDH (glutaryl-CoA dehydrogenase) mutations as a cause of a progressive form of early-onset generalized dystonia.</strong>
|
|
Hum. Genet. 131: 435-442, 2012.
|
|
|
|
|
|
[PubMed: 21912879]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-011-1086-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schwartz, M., Christensen, E., Superti-Furga, A., Brandt, N. J.
|
|
<strong>The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and 13 novel mutations causing glutaric aciduria type I.</strong>
|
|
Hum. Genet. 102: 452-458, 1998.
|
|
|
|
|
|
[PubMed: 9600243]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050720]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strauss, K. A., Lazovic, J., Wintermark, M., Morton, D. H.
|
|
<strong>Multimodal imaging of striatal degeneration in Amish patients with glutaryl-CoA dehydrogenase deficiency.</strong>
|
|
Brain 130: 1905-1920, 2007.
|
|
|
|
|
|
[PubMed: 17478444]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awm058]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zinnanti, W. J., Lazovic, J., Housman, C., LaNoue, K., O'Callaghan, J. P., Simpson, I., Woontner, M., Goodman, S. I., Connor, J. R., Jacobs, R. E., Cheng, K. C.
|
|
<strong>Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I.</strong>
|
|
J. Clin. Invest. 117: 3258-3270, 2007.
|
|
|
|
|
|
[PubMed: 17932566]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI31617]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
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<p class="mim-text-font">
|
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Zinnanti, W. J., Lazovic, J., Wolpert, E. B., Antonetti, D. A., Smith, M. B., Connor, J. R., Woontner, M., Goodman, S. I., Cheng, K. C.
|
|
<strong>A diet-induced mouse model for glutaric aciduria type I.</strong>
|
|
Brain 129: 899-910, 2006.
|
|
|
|
|
|
[PubMed: 16446282]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awl009]
|
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</p>
|
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</li>
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|
|
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<li>
|
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<p class="mim-text-font">
|
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Zschocke, J., Quak, E., Guldberg, P., Hoffmann, G. F.
|
|
<strong>Mutation analysis in glutaric aciduria type I.</strong>
|
|
J. Med. Genet. 37: 177-181, 2000.
|
|
|
|
|
|
[PubMed: 10699052]
|
|
|
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|
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[Full Text: https://doi.org/10.1136/jmg.37.3.177]
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