3873 lines
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Entry
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- *609312 - DOPAMINE BETA-HYDROXYLASE, PLASMA; DBH
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- OMIM
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</form>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*609312</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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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="#geneFunction">Gene Function</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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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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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/609312">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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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=ENSG00000123454;t=ENST00000393056" 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=1621" 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=609312" 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=ENSG00000123454;t=ENST00000393056" 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_000787" 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_000787" 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=609312" 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=01963&isoform_id=01963_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/DBH" 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/30456,30474,30478,16877893,116534900,119608505,158517849" 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/P09172" 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=1621" 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=ENSG00000123454;t=ENST00000393056" 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=DBH" 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=DBH" 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+1621" 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/DBH" 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:1621" 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/1621" 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=chr9&hgg_gene=ENST00000393056.8&hgg_start=133636363&hgg_end=133659329&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:2689" 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://medlineplus.gov/genetics/gene/dbh" 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=609312[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=609312[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000123454" 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=DBH" 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=DBH" 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=DBH" 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="http://www.bh4.org/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=DBH&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/PA136" 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:2689" 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/FBgn0010329.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:94864" 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/DBH#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:94864" 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/1621/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=1621" 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=WBGene00006541;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-990621-3" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1621" 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=DBH&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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609312
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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DOPAMINE BETA-HYDROXYLASE, PLASMA; DBH
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
DOPAMINE BETA-MONOOXYGENASE
|
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</span>
|
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</h4>
|
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</div>
|
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DBH" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DBH</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/9/622?start=-3&limit=10&highlight=622">9q34.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:133636363-133659329&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'})">9:133,636,363-133,659,329</a> </span>
|
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</em>
|
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
|
|
Location
|
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</th>
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<th>
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|
Phenotype
|
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</th>
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
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|
<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/9/622?start=-3&limit=10&highlight=622">
|
|
9q34.2
|
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</a>
|
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</span>
|
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</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Orthostatic hypotension 1, due to DBH deficiency
|
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|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/223360"> 223360 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
|
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</tr>
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</tbody>
|
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</table>
|
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/609312" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/609312" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
|
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<br />
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</div>
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<div>
|
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<p>Dopamine beta-hydroxylase (DBH; <a href="https://enzyme.expasy.org/EC/1.14.17.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.14.17.1</a>) catalyzes the oxidative hydroxylation of dopamine to norepinephrine. It is almost exclusively located in the adrenal medulla and the synaptic vesicles of postganglionic sympathetic neurons (summary by <a href="#13" class="mim-tip-reference" title="Kim, C.-H., Zabetian, C. P., Cubells, J. F., Cho, S., Biaggioni, I., Cohen, B. M., Robertson, D., Kim, K.-S. <strong>Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency.</strong> Am. J. Med. Genet. 108: 140-147, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857564</a>]" pmid="11857564">Kim et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857564" 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="Lamouroux, A., Vigny, A., Faucon Biguet, N., Darmon, M. C., Franck, R., Henry, J.-P., Mallet, J. <strong>The primary structure of human dopamine-beta-hydroxylase: insights into the relationship between the soluble and the membrane-bound forms of the enzyme.</strong> EMBO J. 6: 3931-3937, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3443096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3443096</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1987.tb02734.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3443096">Lamouroux et al. (1987)</a> cloned a full-length cDNA corresponding to dopamine beta-hydroxylase from a human pheochromocytoma lambda cDNA library. The deduced 578-amino acid protein has a molecular mass of approximately 64.8 kD and is preceded by a 25-residue signal peptide that is cleaved. DBH exists in both membrane-bound and soluble forms. Taken together with the biochemical data, the observations suggested that the membrane attachment of DBH probably results from a posttranslational modification, glypiation (glycosylphosphatidylinositolation) being the most likely candidate. Comparative amino acid sequence analysis showed no homology with other catecholamine synthesizing enzymes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3443096" 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="Kobayashi, K., Kurosawa, Y., Fujita, K., Nagatsu, T. <strong>Human dopamine beta-hydroxylase gene: two mRNA types having different 3-prime-terminal regions are produced through alternative polyadenylation.</strong> Nucleic Acids Res. 17: 1089-1102, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2922261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2922261</a>] [<a href="https://doi.org/10.1093/nar/17.3.1089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2922261">Kobayashi et al. (1989)</a> isolated 2 DBH mRNA transcripts: 2.7-kb type A and 2.4-kb type B. The transcripts differed by 300 bp in length and had the same amino acid sequence except for the 3-prime, untranslated region. The findings indicated that alternative use of 2 polyadenylation sites from a single DBH gene generates different mRNA types. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2922261" 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="#14" class="mim-tip-reference" title="Kobayashi, K., Kurosawa, Y., Fujita, K., Nagatsu, T. <strong>Human dopamine beta-hydroxylase gene: two mRNA types having different 3-prime-terminal regions are produced through alternative polyadenylation.</strong> Nucleic Acids Res. 17: 1089-1102, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2922261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2922261</a>] [<a href="https://doi.org/10.1093/nar/17.3.1089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2922261">Kobayashi et al. (1989)</a> determined that the DBH gene has 12 exons and spans 23 kb. Exon 12 encodes the 3-prime-terminal region of 1,013 bp of the type A mRNA, including the 300 bp sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2922261" 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, <a href="#3" class="mim-tip-reference" title="Craig, S. P., Buckle, V. J., Lamouroux, A., Mallet, J., Craig, I. W. <strong>Localization of the human dopamine beta hydroxylase (DBH) gene to chromosome 9q34.</strong> Cytogenet. Cell Genet. 48: 48-50, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3180847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3180847</a>] [<a href="https://doi.org/10.1159/000132584" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3180847">Craig et al. (1988)</a> mapped the DBH gene to chromosome 9q34. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3180847" 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="Pilz, A., Moseley, H., Peters, J., Abbott, C. <strong>Comparative mapping of mouse chromosome 2 and human chromosome 9q: the genes for gelsolin and dopamine beta-hydroxylase map to mouse chromosome 2.</strong> Genomics 12: 715-719, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1315305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1315305</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90300-h" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1315305">Pilz et al. (1992)</a> used interspecies backcrosses to map the mouse Dbh gene to mouse chromosome 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1315305" 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>Joh et al. (<a href="#10" class="mim-tip-reference" title="Joh, T. H., Baetge, E. E., Reis, D. J. <strong>Evidence for the existence of a single gene or linked genes coding for catecholamine biosynthetic enzymes.</strong> Trans. Assoc. Am. Phys. 96: 38-43, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6149647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6149647</a>]" pmid="6149647">1983</a>, <a href="#12" class="mim-tip-reference" title="Joh, T. H., Baetge, E. E., Ross, M. E., Reis, D. J. <strong>Biochemistry and molecular biology of catecholamine neurons: a single gene or gene family hypothesis.</strong> Clin. Exp. Hypertens. A 6: 11-21, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6141853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6141853</a>] [<a href="https://doi.org/10.3109/10641968409062548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6141853">1984</a>) suggested that 3 enzymes of the pathway of catecholamine synthesis, DBH, phenylethanolamine N-methyltransferase (PNMT; <a href="/entry/171190">171190</a>), and tyrosine hydroxylase (TH; <a href="/entry/191290">191290</a>), may be encoded by a single gene or by linked genes derived from a common ancestor. The theory was based on the following observations: (1) proteolytic digestion of these enzymes produces similar peptides whose amino acid composition is nearly identical; (2) antibodies to each enzyme coprecipitate more than 1 of the 3 enzymes from in vitro poly(A)mRNA translation products; (3) DBH cDNA clones cross-hybridize with PNMT mRNA, and PNMT cDNA cross-hybridizes with DBH mRNA, and (4) DBH and PNMT cDNA probes hybridize to several common restriction fragments of total cellular DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6141853+6149647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Orthostatic Hypotension 1</em></strong></p><p>
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In 2 unrelated patients with orthostatic hypotension-1 (ORTHYP1; <a href="/entry/223360">223360</a>) reported by <a href="#22" class="mim-tip-reference" title="Robertson, D., Goldberg, M. R., Onrot, J., Hollister, A. S., Wiley, R., Thompson, J. G., Jr., Robertson, R. M. <strong>Isolated failure of autonomic noradrenergic neurotransmission: evidence for impaired beta-hydroxylation of dopamine.</strong> New Eng. J. Med. 314: 1494-1497, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3010116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3010116</a>] [<a href="https://doi.org/10.1056/NEJM198606053142307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3010116">Robertson et al. (1986)</a> and <a href="#1" class="mim-tip-reference" title="Biaggioni, I., Goldstein, D. S., Atkinson, T., Robertson, D. <strong>Dopamine-beta-hydroxylase deficiency in humans.</strong> Neurology 40: 370-373, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2300263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2300263</a>] [<a href="https://doi.org/10.1212/wnl.40.2.370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2300263">Biaggioni et al. (1990)</a>, <a href="#13" class="mim-tip-reference" title="Kim, C.-H., Zabetian, C. P., Cubells, J. F., Cho, S., Biaggioni, I., Cohen, B. M., Robertson, D., Kim, K.-S. <strong>Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency.</strong> Am. J. Med. Genet. 108: 140-147, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857564</a>]" pmid="11857564">Kim et al. (2002)</a> identified compound heterozygosity for mutations in the DBH gene (<a href="#0002">609312.0002</a>-<a href="#0004">609312.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2300263+11857564+3010116" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Other Disease Associations</em></strong></p><p>
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Plasma DBH activity varies widely between individuals, and a subgroup of the population has very low activity levels. By use of both sequencing-based mutation analysis of extreme phenotypes and genotype-phenotype correlations in samples from African Americans, European Americans, and Japanese, <a href="#28" class="mim-tip-reference" title="Zabetian, C. P., Anderson, G. M., Buxbaum, S. G., Elston, R. C., Ichinose, H., Nagatsu, T., Kim, K.-S., Kim, C.-H., Malison, R. T., Gelernter, J., Cubells, J. F. <strong>A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus.</strong> Am. J. Hum. Genet. 68: 515-522, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11170900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11170900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11170900[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/318198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11170900">Zabetian et al. (2001)</a> identified a novel polymorphism (-1021C-T; <a href="#0001">609312.0001</a>) in the 5-prime flanking region of the DBH gene that accounts for 35 to 52% of the variation in plasma DBH activity in these populations. In European Americans, homozygosity at the T allele predicted the very low DBH activity trait, and activity values in heterozygotes formed an intermediate distribution, indicating codominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11170900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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In a study of 284 individuals from 70 European American pedigrees multiplex for schizophrenia (<a href="/entry/181500">181500</a>), <a href="#6" class="mim-tip-reference" title="Cubells, J. F., Sun, X., Li, W., Bonsall, R. W., McGrath, J. A., Avramopoulos, D., Lasseter, V. K., Wolyniec, P. S., Tang, Y.-L., Mercer, K., Pulver, A. E., Elston, R. C. <strong>Linkage analysis of plasma dopamine beta-hydroxylase activity in families of patients with schizophrenia.</strong> Hum. Genet. 130: 635-643, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21509519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21509519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21509519[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/10.1007/s00439-011-0989-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21509519">Cubells et al. (2011)</a> used linkage analysis with markers on chromosome 9 to confirm an association between plasma DBH activity and SNPs within the DBH gene (maximum multipoint lod score of 6.33 at position 2.8 cM proximal to the DBH gene). Accounting for the contributions to the linkage signal of 3 SNPs at DBH, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1611115;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1611115</a> (<a href="#0001">609312.0001</a>), <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1611122;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1611122</a>, and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6271;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs6271</a>, reduced but did not eliminate the linkage peak, whereas accounting for all SNPs near DBH eliminated the signal entirely. Genomewide SNP analysis provided evidence for linkage to markers at chromosome 20p12 (multipoint lod of 3.1 at 27.2 cM). There was no evidence to support linkage of this trait to chromosome 19. <a href="#6" class="mim-tip-reference" title="Cubells, J. F., Sun, X., Li, W., Bonsall, R. W., McGrath, J. A., Avramopoulos, D., Lasseter, V. K., Wolyniec, P. S., Tang, Y.-L., Mercer, K., Pulver, A. E., Elston, R. C. <strong>Linkage analysis of plasma dopamine beta-hydroxylase activity in families of patients with schizophrenia.</strong> Hum. Genet. 130: 635-643, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21509519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21509519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21509519[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/10.1007/s00439-011-0989-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21509519">Cubells et al. (2011)</a> reviewed previous studies showing an association between variation in plasma levels of DBH activity and expression of psychotic symptoms, and hypothesized that variation in DBH may be a genetic modifier of psychotic symptoms in psychiatric disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21509519" 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="#17" class="mim-tip-reference" title="McKinney, E. F., Walton, R. T., Yudkin, P., Fuller, A., Haldar, N. A., Mant, D., Murphy, M., Welsh, K. I., Marshall, S. E. <strong>Association between polymorphisms in dopamine metabolic enzymes and tobacco consumption in smokers.</strong> Pharmacogenetics 10: 483-491, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10975602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10975602</a>] [<a href="https://doi.org/10.1097/00008571-200008000-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10975602">McKinney et al. (2000)</a> found that allelic variations in the DBH and monoamine oxidase (MAOA; <a href="/entry/309850">309850</a>) genes predicted whether a person was a heavy smoker and how many cigarettes they consumed. More heavy smokers had the DBH 1368A allele when compared to light smokers; conversely, heavy smokers were less likely to have the MAOA 1460C allele. The results supported the view that these enzymes help to determine a smoker's requirement for nicotine and may explain why some people are predisposed to tobacco addiction and why some find it very difficult to stop smoking. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10975602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Lea, R. A., Dohy, A., Jordan, K., Quinlan, S., Brimage, P. J., Griffiths, L. R. <strong>Evidence for allelic association of the dopamine beta-hydroxylase gene (DBH) with susceptibility to typical migraine.</strong> Neurogenetics 3: 35-40, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11085595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11085595</a>] [<a href="https://doi.org/10.1007/pl00022977" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11085595">Lea et al. (2000)</a> tested polymorphisms within the DBH gene as well as within the serotonin transporter (SERT; <a href="/entry/182138">182138</a>) and dopamine receptor (DRD2; <a href="/entry/126450">126450</a>) genes in 177 unrelated Caucasian subjects with migraine and 182 controls. In addition, an independent sample of 82 families affected with migraine was examined. A DBH intragenic dinucleotide polymorphism showed altered allelic distribution between migraine and control groups. The transmission/disequilibrium test, which was implemented on the family data, indicated distortion of allele transmission for the same DBH marker. These results provided evidence for allelic association of the DBH gene with typical migraine susceptibility (<a href="/entry/157300">157300</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11085595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Exclusion Studies</em></strong></p><p>
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By linkage analysis, <a href="#23" class="mim-tip-reference" title="Schuback, D., Kramer, P., Ozelius, L., Holmgren, G., Forsgren, L., Kyllerman, M., Wahlstrom, J., Craft, C. M., Nygaard, T., Brin, M., de Leon, D., Bressman, S., Moskowitz, C. B., Burke, R. E., Sanner, G., Drugge, U., Gusella, J. F., Fahn, S., Breakefield, X. O. <strong>Dopamine beta-hydroxylase gene excluded in four subtypes of hereditary dystonia.</strong> Hum. Genet. 87: 311-316, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1677923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1677923</a>] [<a href="https://doi.org/10.1007/BF00200910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1677923">Schuback et al. (1991)</a> excluded the DBH gene as the site of the mutation in several forms of torsion dystonia (<a href="/entry/128100">128100</a>, <a href="/entry/224500">224500</a>) and in myoclonic dystonia (<a href="/entry/159900">159900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1677923" 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="#24" class="mim-tip-reference" title="Thomas, S. A., Matsumoto, A. M., Palmiter, R. D. <strong>Noradrenaline is essential for mouse fetal development.</strong> Nature 374: 643-646, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7715704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7715704</a>] [<a href="https://doi.org/10.1038/374643a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7715704">Thomas et al. (1995)</a> used gene targeting to produce mice that lack Dbh and are therefore unable to synthesize noradrenaline or adrenaline. They found that in heterozygous mothers, most homozygous embryos died in utero and only about 5% reached adulthood. Survival probably depended on catecholamine transfer across the placenta, because in homozygous mothers all embryos died in utero. Mortality was due to lack of noradrenaline in utero because it could be prevented by treatment with dihydroxyphenylserine (DOPS), a precursor that can be converted to noradrenaline in the absence of DBH. Mutant embryos had a histologic phenotype similar to that of embryos deficient in tyrosine hydroxylase, suggesting that death might be due to cardiovascular failure, as was probably the case with TH-deficient embryos. <a href="#25" class="mim-tip-reference" title="Thomas, S. A., Palmiter, R. D. <strong>Impaired maternal behavior in mice lacking norepinephrine and epinephrine.</strong> Cell 91: 583-592, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9393852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9393852</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80446-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9393852">Thomas and Palmiter (1997)</a> found impaired maternal behavior in these mice with targeted disruption of the Dbh gene. Most heterozygous pups born to Dbh -/- females died within several days of birth and were often found scattered within the bedding. Potential causes, including deficits in olfaction and lactation, were not apparent. A deficit in maternal behavior was confirmed by the lack of pup retrieval exhibited by Dbh -/- virgin females. Restoration of norepinephrine shortly before but not after birth induced females that had previously abandoned their litters to act maternally. These results suggested to the authors that norepinephrine is responsible for long-lasting changes that promote maternal behavior during both development and parturition in mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7715704+9393852" 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>Adrenaline and noradrenaline, the main effectors of the sympathetic nervous system and adrenal medulla, respectively, are thought to control adiposity and energy balance through several mechanisms. They promote catabolism of triglycerides and glycogen, stimulate food intake when injected into the central nervous system, activate thermogenesis in brown adipose tissue, and regulate heat loss through modulation of peripheral vasoconstriction and piloerection. Thermogenesis in brown adipose occurs in response to cold and overeating, and there is an inverse relationship between diet-induced thermogenesis and obesity in both humans and animal models. As a potential model for obesity, <a href="#26" class="mim-tip-reference" title="Thomas, S. A., Palmiter, R. D. <strong>Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline.</strong> Nature 387: 94-97, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9139828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9139828</a>] [<a href="https://doi.org/10.1038/387094a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9139828">Thomas and Palmiter (1997)</a> generated mice that could not synthesize noradrenaline or adrenaline by inactivating the gene that encodes Dbh. These mice were cold intolerant because they had impaired peripheral vasoconstriction and were unable to induce thermogenesis in brown adipose tissue through uncoupling protein (UCP; <a href="/entry/113730">113730</a>). The mutants had increased food intake but did not become obese because their basal metabolic rate (BMR) was also elevated. The unexpected increase in BMR was not due to hyperthyroidism, compensation by the widely expressed UCP2 (<a href="/entry/601693">601693</a>), or shivering. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9139828" 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="#27" class="mim-tip-reference" title="Weinshenker, D., Miller, N. S., Blizinsky, K., Laughlin, M. L., Palmiter, R. D. <strong>Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals.</strong> Proc. Nat. Acad. Sci. 99: 13873-13877, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12370425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12370425</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12370425[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.212519999" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12370425">Weinshenker et al. (2002)</a> took a genetic approach to study how norepinephrine signaling modulates psychostimulant responses by testing locomotor response to amphetamine in dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack norepinephrine. Surprisingly, these null animals were hypersensitive to the behavioral effects of amphetamine. The agent elicited greater locomotor activity in the null mice compared to controls. <a href="#27" class="mim-tip-reference" title="Weinshenker, D., Miller, N. S., Blizinsky, K., Laughlin, M. L., Palmiter, R. D. <strong>Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals.</strong> Proc. Nat. Acad. Sci. 99: 13873-13877, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12370425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12370425</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12370425[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.212519999" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12370425">Weinshenker et al. (2002)</a> noted the observation that cocaine abusers with low-activity DBH haplotypes have increased sensitivity to cocaine-induced paranoia and euphoria (<a href="#5" class="mim-tip-reference" title="Cubells, J. F., Kranzler, H. R., McCance-Katz, E., Anderson, G. M., Malison, R. T., Price, L. H., Gelernter, J. <strong>A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia.</strong> Molec. Psychiat. 5: 56-63, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10673769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10673769</a>] [<a href="https://doi.org/10.1038/sj.mp.4000657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10673769">Cubells et al., 2000</a>), suggesting that DBH enzyme levels modulate both dysphoric and rewarding effects of psychostimulants in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10673769+12370425" 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>It had been hypothesized that the adrenergic nervous system mediates enhanced memory consolidation of emotional events. <a href="#18" class="mim-tip-reference" title="Murchison, C. F., Zhang, X.-Y., Zhang, W.-P., Ouyang, M., Lee, A., Thomas, S. A. <strong>A distinct role for norepinephrine in memory retrieval.</strong> Cell 117: 131-143, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15066288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15066288</a>] [<a href="https://doi.org/10.1016/s0092-8674(04)00259-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15066288">Murchison et al. (2004)</a> tested this hypothesis in several learning tasks using mutant mice conditionally lacking norepinephrine and epinephrine (Dbh -/-), as well as control mice and rats treated with adrenergic receptor agonists and antagonists. Adrenergic signaling was critical for the retrieval of intermediate-term contextual and spatial memories, but was not necessary for the retrieval or consolidation of emotional memories. The role of norepinephrine in retrieval required signaling through the beta-1 adrenergic receptor in the hippocampus. The results demonstrated that mechanisms of memory retrieval can vary over time and can be different from those required for acquisition or consolidation. <a href="#18" class="mim-tip-reference" title="Murchison, C. F., Zhang, X.-Y., Zhang, W.-P., Ouyang, M., Lee, A., Thomas, S. A. <strong>A distinct role for norepinephrine in memory retrieval.</strong> Cell 117: 131-143, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15066288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15066288</a>] [<a href="https://doi.org/10.1016/s0092-8674(04)00259-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15066288">Murchison et al. (2004)</a> concluded that these findings may be relevant to symptoms in several neuropsychiatric disorders as well as the treatment of cardiac failure with beta-blockers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15066288" 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 the tail-suspension test, <a href="#4" class="mim-tip-reference" title="Cryan, J. F., O'Leary, O. F., Jin, S.-H., Friedland, J. C., Ouyang, M., Hirsch, B. R., Page, M. E., Dalvi, A., Thomas, S. A., Lucki, I. <strong>Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.</strong> Proc. Nat. Acad. Sci. 101: 8186-8191, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15148402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15148402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15148402[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0401080101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15148402">Cryan et al. (2004)</a> found that, compared to wildtype mice, Dbh-null mice had reduced sensitivity to several antidepressants, including the norepinephrine reuptake inhibitors desipramine and reboxetine and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine. Reinstitution of norepinephrine in Dbh-null mice reinstated the behavioral effects, demonstrating that the reduced sensitivity was due to decreased norephinephrine function. <a href="#4" class="mim-tip-reference" title="Cryan, J. F., O'Leary, O. F., Jin, S.-H., Friedland, J. C., Ouyang, M., Hirsch, B. R., Page, M. E., Dalvi, A., Thomas, S. A., Lucki, I. <strong>Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.</strong> Proc. Nat. Acad. Sci. 101: 8186-8191, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15148402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15148402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15148402[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0401080101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15148402">Cryan et al. (2004)</a> suggested that norepinephrine plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including SSRIs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15148402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In mice lacking Dbh, an enzyme critical for norepinephrine synthesis, <a href="#20" class="mim-tip-reference" title="Olson, V. G., Heusner, C. L., Bland, R. J., During, M. J., Weinshenker, D., Palmiter, R. D. <strong>Role of noradrenergic signaling by the nucleus tractus solitarius in mediating opiate reward.</strong> Science 311: 1017-1020, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16484499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16484499</a>] [<a href="https://doi.org/10.1126/science.1119311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16484499">Olson et al. (2006)</a> found that norepinephrine was necessary for morphine-induced conditioned place preference (a measure of reward) and locomotion. These deficits were rescued by systemic norepinephrine restoration. Viral restoration of Dbh expression in the nucleus tractus solitarius, but not in the locus ceruleus, restored conditioned place preference for morphine. Morphine-induced locomotion was partially restored by Dbh expression in either brain region. <a href="#20" class="mim-tip-reference" title="Olson, V. G., Heusner, C. L., Bland, R. J., During, M. J., Weinshenker, D., Palmiter, R. D. <strong>Role of noradrenergic signaling by the nucleus tractus solitarius in mediating opiate reward.</strong> Science 311: 1017-1020, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16484499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16484499</a>] [<a href="https://doi.org/10.1126/science.1119311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16484499">Olson et al. (2006)</a> concluded that norepinephrine signaling by the nucleus tractus solitarius is necessary for morphine reward. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16484499" 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 an in silico search, followed by PCR, <a href="#9" class="mim-tip-reference" title="Hejjas, K., Vas, J., Kubinyi, E., Sasvari-Szekely, M., Miklosi, A., Ronai, Z. <strong>Novel repeat polymorphisms of the dopaminergic neurotransmitter genes among dogs and wolves.</strong> Mammalian Genome 18: 871-879, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18049838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18049838</a>] [<a href="https://doi.org/10.1007/s00335-007-9070-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18049838">Hejjas et al. (2007)</a> identified variable number of tandem repeat polymorphisms in genes of the dopaminergic system in 4 dog breeds and European gray wolves. Polymorphisms of the DRD4 (<a href="/entry/126452">126452</a>), DBH, and DAT (SLC6A3; <a href="/entry/126455">126455</a>) genes were associated with attention deficit, but not activity-impulsivity, in Belgian Tervuerens, a breed that had almost all genetic variants identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18049838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>4 Selected Examples</a>):</strong>
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<a href="/allelicVariants/609312" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=609312[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><div class="mim-changed mim-change">.0001 DBH POLYMORPHISM</div></strong>
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DBH, -970C-T (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1611115;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1611115</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1611115 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1611115;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/rs1611115?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=rs1611115" 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=rs1611115" 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=RCV000001819" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001819" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001819</a>
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<p>This polymorphism (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1611115;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1611115</a>) was originally reported as a -1021C-T transition (<a href="#28" class="mim-tip-reference" title="Zabetian, C. P., Anderson, G. M., Buxbaum, S. G., Elston, R. C., Ichinose, H., Nagatsu, T., Kim, K.-S., Kim, C.-H., Malison, R. T., Gelernter, J., Cubells, J. F. <strong>A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus.</strong> Am. J. Hum. Genet. 68: 515-522, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11170900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11170900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11170900[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/318198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11170900">Zabetian et al., 2001</a>), but is now referred to as -970C-T (<a href="#6" class="mim-tip-reference" title="Cubells, J. F., Sun, X., Li, W., Bonsall, R. W., McGrath, J. A., Avramopoulos, D., Lasseter, V. K., Wolyniec, P. S., Tang, Y.-L., Mercer, K., Pulver, A. E., Elston, R. C. <strong>Linkage analysis of plasma dopamine beta-hydroxylase activity in families of patients with schizophrenia.</strong> Hum. Genet. 130: 635-643, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21509519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21509519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21509519[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/10.1007/s00439-011-0989-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21509519">Cubells et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21509519+11170900" 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="#28" class="mim-tip-reference" title="Zabetian, C. P., Anderson, G. M., Buxbaum, S. G., Elston, R. C., Ichinose, H., Nagatsu, T., Kim, K.-S., Kim, C.-H., Malison, R. T., Gelernter, J., Cubells, J. F. <strong>A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus.</strong> Am. J. Hum. Genet. 68: 515-522, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11170900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11170900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11170900[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/318198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11170900">Zabetian et al. (2001)</a> found that a C-to-T polymorphism at nucleotide -1021 in the 5-prime region of the DBH gene was related to dopamine beta-hydroxylase activity levels in plasma. In a study of 174 European Americans, 16 of TT genotype had DBH activity of 4.1; 46 of CT genotype had DBH activity of 25.2; and 112 of CC genotype had DBH activity of 48.1 nmol/min/ml. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11170900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 809 patients with Parkinson disease (<a href="/entry/168600">168600</a>), <a href="#8" class="mim-tip-reference" title="Healy, D. G., Abou-Sleiman, P. M., Ozawa, T., Lees, A. J., Bhatia, K., Ahmadi, K. R., Wullner, U., Berciano, J., Moller, J. C., Kamm, C., Burk, K., Barrone, P., Tolosa, E., Quinn, N., Goldstein, D. B., Wood, N. W. <strong>A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson's disease.</strong> Ann. Neurol. 55: 443-446, 2004. Note: Erratum: Ann. Neurol. 56: 311 only, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14991826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14991826</a>] [<a href="https://doi.org/10.1002/ana.20063" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14991826">Healy et al. (2004)</a> found underrepresentation of the DBH T/T genotype and the T allele compared to controls, suggesting a protective effect of the T allele against the development of PD. Higher serum dopamine levels occurred in individuals with lower DBH activity, corresponding to the T allele. Although no DBH cDNA was amplified from a substantia nigra cDNA library, indicating an absence of protein expression in the substantia nigra, <a href="#8" class="mim-tip-reference" title="Healy, D. G., Abou-Sleiman, P. M., Ozawa, T., Lees, A. J., Bhatia, K., Ahmadi, K. R., Wullner, U., Berciano, J., Moller, J. C., Kamm, C., Burk, K., Barrone, P., Tolosa, E., Quinn, N., Goldstein, D. B., Wood, N. W. <strong>A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson's disease.</strong> Ann. Neurol. 55: 443-446, 2004. Note: Erratum: Ann. Neurol. 56: 311 only, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14991826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14991826</a>] [<a href="https://doi.org/10.1002/ana.20063" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14991826">Healy et al. (2004)</a> suggested that individuals with the low DBH-expressing allele may have higher endogenous dopamine in neurons of the locus ceruleus or elsewhere in the basal ganglia. All 19 chimpanzees tested were homozygous for the C allele, suggesting that the T allele arose in the evolutionary tree between humans and chimpanzees. However, <a href="#2" class="mim-tip-reference" title="Chun, L. S., Samii, A., Hutter, C. M., Griffith, A., Roberts, J. W., Leis, B. C., Mosley, A. D., Wander, P. L., Edwards, K. L., Payami, H., Zabetian, C. P. <strong>DBH -1021C-T does not modify risk or age at onset in Parkinson's disease.</strong> Ann. Neurol. 62: 99-101, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17503507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17503507</a>] [<a href="https://doi.org/10.1002/ana.21149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17503507">Chun et al. (2007)</a> found that the -1021C-T polymorphism did not modify disease risk or age at onset of Parkinson disease in a comparison of 1,244 patients and 1,186 controls of self-defined European American ancestry. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14991826+17503507" 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 675 patients with various forms of epilepsy and over 1,000 control individuals, <a href="#7" class="mim-tip-reference" title="Depondt, C., Cock, H. R., Healy, D. G., Burley, M. W., Weinshenker, D., Wood, N. W., Goldstein, D. B., Sisodiya, S. M. <strong>The -1021C-T DBH gene variant is not associated with epilepsy or antiepileptic drug response.</strong> Neurology 63: 1497-1499, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15505174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15505174</a>] [<a href="https://doi.org/10.1212/01.wnl.0000142092.16719.ad" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15505174">Depondt et al. (2004)</a> found no association between the -1021C-T polymorphism and susceptibility to epilepsy or response to antiepileptic medication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15505174" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 ORTHOSTATIC HYPOTENSION 1</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> rs74853476 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74853476;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/rs74853476?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=rs74853476" 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=rs74853476" 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=RCV000001820 OR RCV000486465" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001820, RCV000486465" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001820...</a>
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<p>In 2 unrelated patients with orthostatic hypotension-1 (ORTHYP1; <a href="/entry/223360">223360</a>), <a href="#13" class="mim-tip-reference" title="Kim, C.-H., Zabetian, C. P., Cubells, J. F., Cho, S., Biaggioni, I., Cohen, B. M., Robertson, D., Kim, K.-S. <strong>Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency.</strong> Am. J. Med. Genet. 108: 140-147, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857564</a>]" pmid="11857564">Kim et al. (2002)</a> identified a heterozygous T-to-C transition in the donor splice site of exon 1 of the DBH gene. Each patient was compound heterozygous for another DBH mutation (<a href="#0003">609312.0003</a> and <a href="#0004">609312.0004</a>, respectively). Functional analysis showed that the mutation resulted in aberrant splicing, although some proper splicing was observed. <a href="#13" class="mim-tip-reference" title="Kim, C.-H., Zabetian, C. P., Cubells, J. F., Cho, S., Biaggioni, I., Cohen, B. M., Robertson, D., Kim, K.-S. <strong>Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency.</strong> Am. J. Med. Genet. 108: 140-147, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857564</a>]" pmid="11857564">Kim et al. (2002)</a> noted that the haplotype containing the splice site mutation in both patients also had the -1021C-T change (<a href="#0001">609312.0001</a>), which had been associated with low plasma DBH, and postulated that the 2 variants together result in DBH protein deficiency. Among 88 healthy unrelated European Americans, the IVS1+2T-C transition had a minor allele frequency of 0.011. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a revised analysis including 801 unrelated adults of African American, European American, and German origin and 260 African American mothers and infants, <a href="#29" class="mim-tip-reference" title="Zabetian, C. P., Romero, R., Robertson, D., Sharma, S., Padbury, J. F., Kuivaniemi, H., Kim, K.-S., Kim, C.-H., Kohnke, M. D., Kranzler, H. R., Gelernter, J., Cubells, J. F. <strong>A revised allele frequency estimate and haplotype analysis of the DBH deficiency mutation IVS1+2T-C in African- and European-Americans. (Letter)</strong> Am. J. Med. Genet. 123A: 190-192, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14598346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14598346</a>] [<a href="https://doi.org/10.1002/ajmg.a.20300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14598346">Zabetian et al. (2003)</a> determined that the frequency of the IVS1+2T-C transition was 0.001. One African American preterm infant was heterozygous for the mutation. Haplotype analysis of the African American infant and the 2 European American patients reported by <a href="#13" class="mim-tip-reference" title="Kim, C.-H., Zabetian, C. P., Cubells, J. F., Cho, S., Biaggioni, I., Cohen, B. M., Robertson, D., Kim, K.-S. <strong>Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency.</strong> Am. J. Med. Genet. 108: 140-147, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857564</a>]" pmid="11857564">Kim et al. (2002)</a> showed that the T-to-C transition arose from a common mutational event. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14598346+11857564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000001821" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001821" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001821</a>
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<p>In a patient with orthostatic hypotension-1 (ORTHYP1; <a href="/entry/223360">223360</a>), <a href="#13" class="mim-tip-reference" title="Kim, C.-H., Zabetian, C. P., Cubells, J. F., Cho, S., Biaggioni, I., Cohen, B. M., Robertson, D., Kim, K.-S. <strong>Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency.</strong> Am. J. Med. Genet. 108: 140-147, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857564</a>]" pmid="11857564">Kim et al. (2002)</a> identified compound heterozygosity for 2 mutations in the DBH gene: one allele had a 300C-A transversion in exon 2, resulting in an asp100-to-glu (D100E) substitution in a highly conserved region; the second allele contained a splice site mutation (<a href="#0002">609312.0002</a>). Each of the patient's parents was heterozygous for 1 of the mutations, and the D100E mutation was not identified in 88 control individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857564" 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> rs267606760 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606760;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/rs267606760?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=rs267606760" 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=rs267606760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs267606761 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606761;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/rs267606761?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=rs267606761" 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=rs267606761" 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=RCV000001822 OR RCV000201811 OR RCV000201816" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001822, RCV000201811, RCV000201816" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001822...</a>
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<p>In a patient with orthostatic hypotension-1 (ORTHYP1; <a href="/entry/223360">223360</a>), <a href="#13" class="mim-tip-reference" title="Kim, C.-H., Zabetian, C. P., Cubells, J. F., Cho, S., Biaggioni, I., Cohen, B. M., Robertson, D., Kim, K.-S. <strong>Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency.</strong> Am. J. Med. Genet. 108: 140-147, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857564</a>]" pmid="11857564">Kim et al. (2002)</a> identified compound heterozygosity for mutations in both alleles of the DBH gene: one allele, inherited from the mother, contained a 259G-A transition in exon 1, resulting in a val87-to-met (V87M) substitution, and a 991G-A transition in exon 6, resulting in an asp331-to-asn (D331N) substitution in cis; the other allele, inherited from the father, had a splice site mutation (<a href="#0002">609312.0002</a>). Species comparison showed that residue 331 is highly conserved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857564" 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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<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<strong>See Also:</strong>
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<a href="#Joh1983" class="mim-tip-reference" title="Joh, T. H., Baetge, E. E., Ross, M. E., Albert, V. R., Moon, H. M., Reis, D. J. <strong>Existence of catecholamine biosynthetic enzyme gene family. (Abstract)</strong> Clin. Res. 31: 528 only, 1983.">Joh et al. (1983)</a>; <a href="#O'Malley1983" class="mim-tip-reference" title="O'Malley, K. L., Mauron, A., Raese, J., Barchas, J. D., Kedes, L. <strong>Genes for catecholamine biosynthesis: cloning by expression and identification of the cDNA for rat dopamine beta-hydroxylase.</strong> Proc. Nat. Acad. Sci. 80: 2161-2165, 1983.">O'Malley et al. (1983)</a>
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<strong>REFERENCES</strong>
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</span>
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<a id="1" class="mim-anchor"></a>
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<a id="Biaggioni1990" class="mim-anchor"></a>
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Biaggioni, I., Goldstein, D. S., Atkinson, T., Robertson, D.
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<strong>Dopamine-beta-hydroxylase deficiency in humans.</strong>
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Neurology 40: 370-373, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2300263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2300263</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2300263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.40.2.370" target="_blank">Full Text</a>]
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<a id="Chun2007" class="mim-anchor"></a>
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Chun, L. S., Samii, A., Hutter, C. M., Griffith, A., Roberts, J. W., Leis, B. C., Mosley, A. D., Wander, P. L., Edwards, K. L., Payami, H., Zabetian, C. P.
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<strong>DBH -1021C-T does not modify risk or age at onset in Parkinson's disease.</strong>
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Ann. Neurol. 62: 99-101, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17503507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17503507</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17503507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.21149" target="_blank">Full Text</a>]
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<a id="Craig1988" class="mim-anchor"></a>
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Craig, S. P., Buckle, V. J., Lamouroux, A., Mallet, J., Craig, I. W.
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<strong>Localization of the human dopamine beta hydroxylase (DBH) gene to chromosome 9q34.</strong>
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Cytogenet. Cell Genet. 48: 48-50, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3180847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3180847</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3180847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000132584" target="_blank">Full Text</a>]
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<a id="Cryan2004" class="mim-anchor"></a>
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Cryan, J. F., O'Leary, O. F., Jin, S.-H., Friedland, J. C., Ouyang, M., Hirsch, B. R., Page, M. E., Dalvi, A., Thomas, S. A., Lucki, I.
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<strong>Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.</strong>
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Proc. Nat. Acad. Sci. 101: 8186-8191, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15148402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15148402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15148402[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=15148402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0401080101" target="_blank">Full Text</a>]
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<a id="Cubells2000" class="mim-anchor"></a>
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Cubells, J. F., Kranzler, H. R., McCance-Katz, E., Anderson, G. M., Malison, R. T., Price, L. H., Gelernter, J.
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<strong>A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia.</strong>
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Molec. Psychiat. 5: 56-63, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10673769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10673769</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10673769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.mp.4000657" target="_blank">Full Text</a>]
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<a id="Cubells2011" class="mim-anchor"></a>
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Cubells, J. F., Sun, X., Li, W., Bonsall, R. W., McGrath, J. A., Avramopoulos, D., Lasseter, V. K., Wolyniec, P. S., Tang, Y.-L., Mercer, K., Pulver, A. E., Elston, R. C.
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<strong>Linkage analysis of plasma dopamine beta-hydroxylase activity in families of patients with schizophrenia.</strong>
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Hum. Genet. 130: 635-643, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21509519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21509519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21509519[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=21509519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-011-0989-6" target="_blank">Full Text</a>]
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<a id="Depondt2004" class="mim-anchor"></a>
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Depondt, C., Cock, H. R., Healy, D. G., Burley, M. W., Weinshenker, D., Wood, N. W., Goldstein, D. B., Sisodiya, S. M.
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<strong>The -1021C-T DBH gene variant is not associated with epilepsy or antiepileptic drug response.</strong>
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Neurology 63: 1497-1499, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15505174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15505174</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15505174" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000142092.16719.ad" target="_blank">Full Text</a>]
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<a id="Healy2004" class="mim-anchor"></a>
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Healy, D. G., Abou-Sleiman, P. M., Ozawa, T., Lees, A. J., Bhatia, K., Ahmadi, K. R., Wullner, U., Berciano, J., Moller, J. C., Kamm, C., Burk, K., Barrone, P., Tolosa, E., Quinn, N., Goldstein, D. B., Wood, N. W.
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<strong>A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson's disease.</strong>
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Ann. Neurol. 55: 443-446, 2004. Note: Erratum: Ann. Neurol. 56: 311 only, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14991826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14991826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14991826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.20063" target="_blank">Full Text</a>]
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<a id="Hejjas2007" class="mim-anchor"></a>
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Hejjas, K., Vas, J., Kubinyi, E., Sasvari-Szekely, M., Miklosi, A., Ronai, Z.
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<strong>Novel repeat polymorphisms of the dopaminergic neurotransmitter genes among dogs and wolves.</strong>
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Mammalian Genome 18: 871-879, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18049838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18049838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18049838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12370425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12370425</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12370425[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=12370425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.212519999" target="_blank">Full Text</a>]
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</p>
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<a id="28" class="mim-anchor"></a>
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<a id="Zabetian2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zabetian, C. P., Anderson, G. M., Buxbaum, S. G., Elston, R. C., Ichinose, H., Nagatsu, T., Kim, K.-S., Kim, C.-H., Malison, R. T., Gelernter, J., Cubells, J. F.
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<strong>A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus.</strong>
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Am. J. Hum. Genet. 68: 515-522, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11170900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11170900</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11170900[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=11170900" 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/10.1086/318198" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="29" class="mim-anchor"></a>
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<a id="Zabetian2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zabetian, C. P., Romero, R., Robertson, D., Sharma, S., Padbury, J. F., Kuivaniemi, H., Kim, K.-S., Kim, C.-H., Kohnke, M. D., Kranzler, H. R., Gelernter, J., Cubells, J. F.
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<strong>A revised allele frequency estimate and haplotype analysis of the DBH deficiency mutation IVS1+2T-C in African- and European-Americans. (Letter)</strong>
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Am. J. Med. Genet. 123A: 190-192, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14598346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14598346</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14598346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.20300" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 12/19/2011
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 10/24/2008<br>Cassandra L. Kniffin - updated : 12/26/2007<br>Ada Hamosh - updated : 5/1/2006<br>Cassandra L. Kniffin -updated : 10/3/2005<br>Cassandra L. Kniffin - updated : 9/12/2005
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin : 4/15/2005
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 01/07/2025
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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carol : 11/14/2018<br>carol : 11/14/2018<br>ckniffin : 11/12/2018<br>joanna : 08/01/2016<br>carol : 04/12/2016<br>carol : 1/20/2012<br>ckniffin : 12/19/2011<br>ckniffin : 11/16/2010<br>wwang : 12/11/2009<br>wwang : 4/16/2009<br>mgross : 10/24/2008<br>mgross : 10/24/2008<br>wwang : 1/15/2008<br>ckniffin : 12/26/2007<br>carol : 5/31/2007<br>carol : 6/21/2006<br>alopez : 5/3/2006<br>terry : 5/1/2006<br>wwang : 10/17/2005<br>ckniffin : 10/3/2005<br>wwang : 9/19/2005<br>ckniffin : 9/12/2005<br>tkritzer : 4/19/2005<br>ckniffin : 4/18/2005
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<span class="mim-font">
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<strong>*</strong> 609312
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<div>
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<h3>
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<span class="mim-font">
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DOPAMINE BETA-HYDROXYLASE, PLASMA; DBH
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</h3>
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</div>
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<div>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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DOPAMINE BETA-MONOOXYGENASE
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</h4>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: DBH</em></strong>
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<strong>
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<em>
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Cytogenetic location: 9q34.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 9:133,636,363-133,659,329 </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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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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Location
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Phenotype
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</th>
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<td rowspan="1">
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<span class="mim-font">
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9q34.2
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<td>
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<span class="mim-font">
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Orthostatic hypotension 1, due to DBH deficiency
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</td>
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<td>
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<span class="mim-font">
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223360
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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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<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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<span class="mim-font">
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<strong>Description</strong>
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</div>
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<span class="mim-text-font">
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<p>Dopamine beta-hydroxylase (DBH; EC 1.14.17.1) catalyzes the oxidative hydroxylation of dopamine to norepinephrine. It is almost exclusively located in the adrenal medulla and the synaptic vesicles of postganglionic sympathetic neurons (summary by Kim et al., 2002). </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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<span class="mim-text-font">
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<p>Lamouroux et al. (1987) cloned a full-length cDNA corresponding to dopamine beta-hydroxylase from a human pheochromocytoma lambda cDNA library. The deduced 578-amino acid protein has a molecular mass of approximately 64.8 kD and is preceded by a 25-residue signal peptide that is cleaved. DBH exists in both membrane-bound and soluble forms. Taken together with the biochemical data, the observations suggested that the membrane attachment of DBH probably results from a posttranslational modification, glypiation (glycosylphosphatidylinositolation) being the most likely candidate. Comparative amino acid sequence analysis showed no homology with other catecholamine synthesizing enzymes. </p><p>Kobayashi et al. (1989) isolated 2 DBH mRNA transcripts: 2.7-kb type A and 2.4-kb type B. The transcripts differed by 300 bp in length and had the same amino acid sequence except for the 3-prime, untranslated region. The findings indicated that alternative use of 2 polyadenylation sites from a single DBH gene generates different mRNA types. </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>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kobayashi et al. (1989) determined that the DBH gene has 12 exons and spans 23 kb. Exon 12 encodes the 3-prime-terminal region of 1,013 bp of the type A mRNA, including the 300 bp sequence. </p>
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</span>
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<div>
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<br />
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</div>
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<h4>
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<span class="mim-font">
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<strong>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, Craig et al. (1988) mapped the DBH gene to chromosome 9q34. </p><p>Pilz et al. (1992) used interspecies backcrosses to map the mouse Dbh gene to mouse chromosome 2. </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Joh et al. (1983, 1984) suggested that 3 enzymes of the pathway of catecholamine synthesis, DBH, phenylethanolamine N-methyltransferase (PNMT; 171190), and tyrosine hydroxylase (TH; 191290), may be encoded by a single gene or by linked genes derived from a common ancestor. The theory was based on the following observations: (1) proteolytic digestion of these enzymes produces similar peptides whose amino acid composition is nearly identical; (2) antibodies to each enzyme coprecipitate more than 1 of the 3 enzymes from in vitro poly(A)mRNA translation products; (3) DBH cDNA clones cross-hybridize with PNMT mRNA, and PNMT cDNA cross-hybridizes with DBH mRNA, and (4) DBH and PNMT cDNA probes hybridize to several common restriction fragments of total cellular DNA. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Orthostatic Hypotension 1</em></strong></p><p>
|
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In 2 unrelated patients with orthostatic hypotension-1 (ORTHYP1; 223360) reported by Robertson et al. (1986) and Biaggioni et al. (1990), Kim et al. (2002) identified compound heterozygosity for mutations in the DBH gene (609312.0002-609312.0004). </p><p><strong><em>Other Disease Associations</em></strong></p><p>
|
|
Plasma DBH activity varies widely between individuals, and a subgroup of the population has very low activity levels. By use of both sequencing-based mutation analysis of extreme phenotypes and genotype-phenotype correlations in samples from African Americans, European Americans, and Japanese, Zabetian et al. (2001) identified a novel polymorphism (-1021C-T; 609312.0001) in the 5-prime flanking region of the DBH gene that accounts for 35 to 52% of the variation in plasma DBH activity in these populations. In European Americans, homozygosity at the T allele predicted the very low DBH activity trait, and activity values in heterozygotes formed an intermediate distribution, indicating codominant inheritance. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
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In a study of 284 individuals from 70 European American pedigrees multiplex for schizophrenia (181500), Cubells et al. (2011) used linkage analysis with markers on chromosome 9 to confirm an association between plasma DBH activity and SNPs within the DBH gene (maximum multipoint lod score of 6.33 at position 2.8 cM proximal to the DBH gene). Accounting for the contributions to the linkage signal of 3 SNPs at DBH, rs1611115 (609312.0001), rs1611122, and rs6271, reduced but did not eliminate the linkage peak, whereas accounting for all SNPs near DBH eliminated the signal entirely. Genomewide SNP analysis provided evidence for linkage to markers at chromosome 20p12 (multipoint lod of 3.1 at 27.2 cM). There was no evidence to support linkage of this trait to chromosome 19. Cubells et al. (2011) reviewed previous studies showing an association between variation in plasma levels of DBH activity and expression of psychotic symptoms, and hypothesized that variation in DBH may be a genetic modifier of psychotic symptoms in psychiatric disorders. </p><p>McKinney et al. (2000) found that allelic variations in the DBH and monoamine oxidase (MAOA; 309850) genes predicted whether a person was a heavy smoker and how many cigarettes they consumed. More heavy smokers had the DBH 1368A allele when compared to light smokers; conversely, heavy smokers were less likely to have the MAOA 1460C allele. The results supported the view that these enzymes help to determine a smoker's requirement for nicotine and may explain why some people are predisposed to tobacco addiction and why some find it very difficult to stop smoking. </p><p>Lea et al. (2000) tested polymorphisms within the DBH gene as well as within the serotonin transporter (SERT; 182138) and dopamine receptor (DRD2; 126450) genes in 177 unrelated Caucasian subjects with migraine and 182 controls. In addition, an independent sample of 82 families affected with migraine was examined. A DBH intragenic dinucleotide polymorphism showed altered allelic distribution between migraine and control groups. The transmission/disequilibrium test, which was implemented on the family data, indicated distortion of allele transmission for the same DBH marker. These results provided evidence for allelic association of the DBH gene with typical migraine susceptibility (157300). </p><p><strong><em>Exclusion Studies</em></strong></p><p>
|
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By linkage analysis, Schuback et al. (1991) excluded the DBH gene as the site of the mutation in several forms of torsion dystonia (128100, 224500) and in myoclonic dystonia (159900). </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</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>Thomas et al. (1995) used gene targeting to produce mice that lack Dbh and are therefore unable to synthesize noradrenaline or adrenaline. They found that in heterozygous mothers, most homozygous embryos died in utero and only about 5% reached adulthood. Survival probably depended on catecholamine transfer across the placenta, because in homozygous mothers all embryos died in utero. Mortality was due to lack of noradrenaline in utero because it could be prevented by treatment with dihydroxyphenylserine (DOPS), a precursor that can be converted to noradrenaline in the absence of DBH. Mutant embryos had a histologic phenotype similar to that of embryos deficient in tyrosine hydroxylase, suggesting that death might be due to cardiovascular failure, as was probably the case with TH-deficient embryos. Thomas and Palmiter (1997) found impaired maternal behavior in these mice with targeted disruption of the Dbh gene. Most heterozygous pups born to Dbh -/- females died within several days of birth and were often found scattered within the bedding. Potential causes, including deficits in olfaction and lactation, were not apparent. A deficit in maternal behavior was confirmed by the lack of pup retrieval exhibited by Dbh -/- virgin females. Restoration of norepinephrine shortly before but not after birth induced females that had previously abandoned their litters to act maternally. These results suggested to the authors that norepinephrine is responsible for long-lasting changes that promote maternal behavior during both development and parturition in mice. </p><p>Adrenaline and noradrenaline, the main effectors of the sympathetic nervous system and adrenal medulla, respectively, are thought to control adiposity and energy balance through several mechanisms. They promote catabolism of triglycerides and glycogen, stimulate food intake when injected into the central nervous system, activate thermogenesis in brown adipose tissue, and regulate heat loss through modulation of peripheral vasoconstriction and piloerection. Thermogenesis in brown adipose occurs in response to cold and overeating, and there is an inverse relationship between diet-induced thermogenesis and obesity in both humans and animal models. As a potential model for obesity, Thomas and Palmiter (1997) generated mice that could not synthesize noradrenaline or adrenaline by inactivating the gene that encodes Dbh. These mice were cold intolerant because they had impaired peripheral vasoconstriction and were unable to induce thermogenesis in brown adipose tissue through uncoupling protein (UCP; 113730). The mutants had increased food intake but did not become obese because their basal metabolic rate (BMR) was also elevated. The unexpected increase in BMR was not due to hyperthyroidism, compensation by the widely expressed UCP2 (601693), or shivering. </p><p>Weinshenker et al. (2002) took a genetic approach to study how norepinephrine signaling modulates psychostimulant responses by testing locomotor response to amphetamine in dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack norepinephrine. Surprisingly, these null animals were hypersensitive to the behavioral effects of amphetamine. The agent elicited greater locomotor activity in the null mice compared to controls. Weinshenker et al. (2002) noted the observation that cocaine abusers with low-activity DBH haplotypes have increased sensitivity to cocaine-induced paranoia and euphoria (Cubells et al., 2000), suggesting that DBH enzyme levels modulate both dysphoric and rewarding effects of psychostimulants in humans. </p><p>It had been hypothesized that the adrenergic nervous system mediates enhanced memory consolidation of emotional events. Murchison et al. (2004) tested this hypothesis in several learning tasks using mutant mice conditionally lacking norepinephrine and epinephrine (Dbh -/-), as well as control mice and rats treated with adrenergic receptor agonists and antagonists. Adrenergic signaling was critical for the retrieval of intermediate-term contextual and spatial memories, but was not necessary for the retrieval or consolidation of emotional memories. The role of norepinephrine in retrieval required signaling through the beta-1 adrenergic receptor in the hippocampus. The results demonstrated that mechanisms of memory retrieval can vary over time and can be different from those required for acquisition or consolidation. Murchison et al. (2004) concluded that these findings may be relevant to symptoms in several neuropsychiatric disorders as well as the treatment of cardiac failure with beta-blockers. </p><p>Using the tail-suspension test, Cryan et al. (2004) found that, compared to wildtype mice, Dbh-null mice had reduced sensitivity to several antidepressants, including the norepinephrine reuptake inhibitors desipramine and reboxetine and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine. Reinstitution of norepinephrine in Dbh-null mice reinstated the behavioral effects, demonstrating that the reduced sensitivity was due to decreased norephinephrine function. Cryan et al. (2004) suggested that norepinephrine plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including SSRIs. </p><p>In mice lacking Dbh, an enzyme critical for norepinephrine synthesis, Olson et al. (2006) found that norepinephrine was necessary for morphine-induced conditioned place preference (a measure of reward) and locomotion. These deficits were rescued by systemic norepinephrine restoration. Viral restoration of Dbh expression in the nucleus tractus solitarius, but not in the locus ceruleus, restored conditioned place preference for morphine. Morphine-induced locomotion was partially restored by Dbh expression in either brain region. Olson et al. (2006) concluded that norepinephrine signaling by the nucleus tractus solitarius is necessary for morphine reward. </p><p>Using an in silico search, followed by PCR, Hejjas et al. (2007) identified variable number of tandem repeat polymorphisms in genes of the dopaminergic system in 4 dog breeds and European gray wolves. Polymorphisms of the DRD4 (126452), DBH, and DAT (SLC6A3; 126455) genes were associated with attention deficit, but not activity-impulsivity, in Belgian Tervuerens, a breed that had almost all genetic variants identified. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>4 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 DBH POLYMORPHISM</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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DBH, -970C-T ({dbSNP rs1611115})
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<br />
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SNP: rs1611115,
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gnomAD: rs1611115,
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ClinVar: RCV000001819
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</span>
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<span class="mim-text-font">
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<p>This polymorphism (rs1611115) was originally reported as a -1021C-T transition (Zabetian et al., 2001), but is now referred to as -970C-T (Cubells et al., 2011). </p><p>Zabetian et al. (2001) found that a C-to-T polymorphism at nucleotide -1021 in the 5-prime region of the DBH gene was related to dopamine beta-hydroxylase activity levels in plasma. In a study of 174 European Americans, 16 of TT genotype had DBH activity of 4.1; 46 of CT genotype had DBH activity of 25.2; and 112 of CC genotype had DBH activity of 48.1 nmol/min/ml. </p><p>In 809 patients with Parkinson disease (168600), Healy et al. (2004) found underrepresentation of the DBH T/T genotype and the T allele compared to controls, suggesting a protective effect of the T allele against the development of PD. Higher serum dopamine levels occurred in individuals with lower DBH activity, corresponding to the T allele. Although no DBH cDNA was amplified from a substantia nigra cDNA library, indicating an absence of protein expression in the substantia nigra, Healy et al. (2004) suggested that individuals with the low DBH-expressing allele may have higher endogenous dopamine in neurons of the locus ceruleus or elsewhere in the basal ganglia. All 19 chimpanzees tested were homozygous for the C allele, suggesting that the T allele arose in the evolutionary tree between humans and chimpanzees. However, Chun et al. (2007) found that the -1021C-T polymorphism did not modify disease risk or age at onset of Parkinson disease in a comparison of 1,244 patients and 1,186 controls of self-defined European American ancestry. </p><p>Among 675 patients with various forms of epilepsy and over 1,000 control individuals, Depondt et al. (2004) found no association between the -1021C-T polymorphism and susceptibility to epilepsy or response to antiepileptic medication. </p>
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</span>
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<div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 ORTHOSTATIC HYPOTENSION 1</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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DBH, IVS1DS, T-C, +2
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<br />
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SNP: rs74853476,
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gnomAD: rs74853476,
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ClinVar: RCV000001820, RCV000486465
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated patients with orthostatic hypotension-1 (ORTHYP1; 223360), Kim et al. (2002) identified a heterozygous T-to-C transition in the donor splice site of exon 1 of the DBH gene. Each patient was compound heterozygous for another DBH mutation (609312.0003 and 609312.0004, respectively). Functional analysis showed that the mutation resulted in aberrant splicing, although some proper splicing was observed. Kim et al. (2002) noted that the haplotype containing the splice site mutation in both patients also had the -1021C-T change (609312.0001), which had been associated with low plasma DBH, and postulated that the 2 variants together result in DBH protein deficiency. Among 88 healthy unrelated European Americans, the IVS1+2T-C transition had a minor allele frequency of 0.011. </p><p>In a revised analysis including 801 unrelated adults of African American, European American, and German origin and 260 African American mothers and infants, Zabetian et al. (2003) determined that the frequency of the IVS1+2T-C transition was 0.001. One African American preterm infant was heterozygous for the mutation. Haplotype analysis of the African American infant and the 2 European American patients reported by Kim et al. (2002) showed that the T-to-C transition arose from a common mutational event. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 ORTHOSTATIC HYPOTENSION 1</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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DBH, ASP100GLU
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<br />
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SNP: rs77576840,
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gnomAD: rs77576840,
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ClinVar: RCV000001821
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with orthostatic hypotension-1 (ORTHYP1; 223360), Kim et al. (2002) identified compound heterozygosity for 2 mutations in the DBH gene: one allele had a 300C-A transversion in exon 2, resulting in an asp100-to-glu (D100E) substitution in a highly conserved region; the second allele contained a splice site mutation (609312.0002). Each of the patient's parents was heterozygous for 1 of the mutations, and the D100E mutation was not identified in 88 control individuals. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 ORTHOSTATIC HYPOTENSION 1</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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DBH, VAL87MET AND ASP331ASN
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<br />
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SNP: rs267606760, rs267606761,
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gnomAD: rs267606760, rs267606761,
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ClinVar: RCV000001822, RCV000201811, RCV000201816
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with orthostatic hypotension-1 (ORTHYP1; 223360), Kim et al. (2002) identified compound heterozygosity for mutations in both alleles of the DBH gene: one allele, inherited from the mother, contained a 259G-A transition in exon 1, resulting in a val87-to-met (V87M) substitution, and a 991G-A transition in exon 6, resulting in an asp331-to-asn (D331N) substitution in cis; the other allele, inherited from the father, had a splice site mutation (609312.0002). Species comparison showed that residue 331 is highly conserved. </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>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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|
Joh et al. (1983); O'Malley et al. (1983)
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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|
<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Biaggioni, I., Goldstein, D. S., Atkinson, T., Robertson, D.
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<strong>Dopamine-beta-hydroxylase deficiency in humans.</strong>
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Neurology 40: 370-373, 1990.
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[PubMed: 2300263]
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[Full Text: https://doi.org/10.1212/wnl.40.2.370]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Chun, L. S., Samii, A., Hutter, C. M., Griffith, A., Roberts, J. W., Leis, B. C., Mosley, A. D., Wander, P. L., Edwards, K. L., Payami, H., Zabetian, C. P.
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<strong>DBH -1021C-T does not modify risk or age at onset in Parkinson's disease.</strong>
|
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Ann. Neurol. 62: 99-101, 2007.
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[PubMed: 17503507]
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[Full Text: https://doi.org/10.1002/ana.21149]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Craig, S. P., Buckle, V. J., Lamouroux, A., Mallet, J., Craig, I. W.
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<strong>Localization of the human dopamine beta hydroxylase (DBH) gene to chromosome 9q34.</strong>
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Cytogenet. Cell Genet. 48: 48-50, 1988.
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[PubMed: 3180847]
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[Full Text: https://doi.org/10.1159/000132584]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Cryan, J. F., O'Leary, O. F., Jin, S.-H., Friedland, J. C., Ouyang, M., Hirsch, B. R., Page, M. E., Dalvi, A., Thomas, S. A., Lucki, I.
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<strong>Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.</strong>
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Proc. Nat. Acad. Sci. 101: 8186-8191, 2004.
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[PubMed: 15148402]
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[Full Text: https://doi.org/10.1073/pnas.0401080101]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Cubells, J. F., Kranzler, H. R., McCance-Katz, E., Anderson, G. M., Malison, R. T., Price, L. H., Gelernter, J.
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<strong>A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia.</strong>
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Molec. Psychiat. 5: 56-63, 2000.
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[PubMed: 10673769]
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[Full Text: https://doi.org/10.1038/sj.mp.4000657]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Cubells, J. F., Sun, X., Li, W., Bonsall, R. W., McGrath, J. A., Avramopoulos, D., Lasseter, V. K., Wolyniec, P. S., Tang, Y.-L., Mercer, K., Pulver, A. E., Elston, R. C.
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<strong>Linkage analysis of plasma dopamine beta-hydroxylase activity in families of patients with schizophrenia.</strong>
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Hum. Genet. 130: 635-643, 2011.
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[PubMed: 21509519]
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[Full Text: https://doi.org/10.1007/s00439-011-0989-6]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Depondt, C., Cock, H. R., Healy, D. G., Burley, M. W., Weinshenker, D., Wood, N. W., Goldstein, D. B., Sisodiya, S. M.
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<strong>The -1021C-T DBH gene variant is not associated with epilepsy or antiepileptic drug response.</strong>
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Neurology 63: 1497-1499, 2004.
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[PubMed: 15505174]
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[Full Text: https://doi.org/10.1212/01.wnl.0000142092.16719.ad]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Healy, D. G., Abou-Sleiman, P. M., Ozawa, T., Lees, A. J., Bhatia, K., Ahmadi, K. R., Wullner, U., Berciano, J., Moller, J. C., Kamm, C., Burk, K., Barrone, P., Tolosa, E., Quinn, N., Goldstein, D. B., Wood, N. W.
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<strong>A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson's disease.</strong>
|
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Ann. Neurol. 55: 443-446, 2004. Note: Erratum: Ann. Neurol. 56: 311 only, 2004.
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[PubMed: 14991826]
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[Full Text: https://doi.org/10.1002/ana.20063]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hejjas, K., Vas, J., Kubinyi, E., Sasvari-Szekely, M., Miklosi, A., Ronai, Z.
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<strong>Novel repeat polymorphisms of the dopaminergic neurotransmitter genes among dogs and wolves.</strong>
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Mammalian Genome 18: 871-879, 2007.
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[PubMed: 18049838]
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[Full Text: https://doi.org/10.1007/s00335-007-9070-0]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Joh, T. H., Baetge, E. E., Reis, D. J.
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<strong>Evidence for the existence of a single gene or linked genes coding for catecholamine biosynthetic enzymes.</strong>
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Trans. Assoc. Am. Phys. 96: 38-43, 1983.
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[PubMed: 6149647]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Joh, T. H., Baetge, E. E., Ross, M. E., Albert, V. R., Moon, H. M., Reis, D. J.
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<strong>Existence of catecholamine biosynthetic enzyme gene family. (Abstract)</strong>
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Clin. Res. 31: 528 only, 1983.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Joh, T. H., Baetge, E. E., Ross, M. E., Reis, D. J.
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<strong>Biochemistry and molecular biology of catecholamine neurons: a single gene or gene family hypothesis.</strong>
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Clin. Exp. Hypertens. A 6: 11-21, 1984.
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[PubMed: 6141853]
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[Full Text: https://doi.org/10.3109/10641968409062548]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Kim, C.-H., Zabetian, C. P., Cubells, J. F., Cho, S., Biaggioni, I., Cohen, B. M., Robertson, D., Kim, K.-S.
|
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<strong>Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency.</strong>
|
|
Am. J. Med. Genet. 108: 140-147, 2002.
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[PubMed: 11857564]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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