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Entry
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- *600293 - ADENYLATE CYCLASE 5; ADCY5
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*600293</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<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/600293">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</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=ENSG00000173175;t=ENST00000462833" 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=111" 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=600293" 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=ENSG00000173175;t=ENST00000462833" 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_001199642,NM_001378259,NM_183357,XM_005247078,XM_006713483,XM_006713484,XM_011512359,XM_011512360,XM_011512361,XM_017005638,XM_017005639,XM_047447359,XM_047447360,XM_047447361,XM_047447362,XM_047447363,XM_047447364,XM_047447365" 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_183357" 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=600293" 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=08973&isoform_id=08973_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/ADCY5" 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/4097594,22212711,22212913,34486092,118572619,119599856,193784917,193787564,221040100,221044220,221044430,221046364,308219912,314122162,530373840,578807015,578807017,767925564,767925566,767925568,1034630961,1034630964,1805791150,2217341573,2217341576,2217341578,2217341580,2217341584,2217341586,2217341588,2462586755,2462586757,2462586759,2462586761,2462586764,2462586766,2462586768,2462586770,2462586772,2462586774,2462586776,2462586778,2462586780,2462586782,2462586784" 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/O95622" 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=111" 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=ENSG00000173175;t=ENST00000462833" 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=ADCY5" 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=ADCY5" 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+111" 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/ADCY5" 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:111" 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/111" 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=chr3&hgg_gene=ENST00000462833.6&hgg_start=123282296&hgg_end=123449090&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://medlineplus.gov/genetics/gene/adcy5" 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=600293[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=600293[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/ADCY5/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000173175" 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=ADCY5" 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=ADCY5" 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=ADCY5" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ADCY5&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/PA24563" 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:236" 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/FBgn0263131.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:99673" 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/ADCY5#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:99673" 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/111/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=111" 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=WBGene00000071;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-081104-470" 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">
|
|
<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:111" 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=ADCY5&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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600293
|
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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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ADENYLATE CYCLASE 5; ADCY5
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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">
|
|
ADENYLYL CYCLASE 5
|
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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=ADCY5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ADCY5</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/3/619?start=-3&limit=10&highlight=619">3q21.1</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:123282296-123449090&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'})">3:123,282,296-123,449,090</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=606703,619647,619651" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/3/619?start=-3&limit=10&highlight=619">
|
|
3q21.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Dyskinesia with orofacial involvement, autosomal dominant
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/606703"> 606703 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
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|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Dyskinesia with orofacial involvement, autosomal recessive
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/619647"> 619647 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Neurodevelopmental disorder with hyperkinetic movements and dyskinesia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
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<a href="/entry/619651"> 619651 </a>
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PheneGene Graphics <span class="caret"></span>
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<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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<p>ADCY5 belongs to the adenylate cyclase (<a href="https://enzyme.expasy.org/EC/4.6.1.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 4.6.1.1</a>) family of enzymes responsible for the synthesis of cAMP (<a href="#18" class="mim-tip-reference" title="Ludwig, M.-G., Seuwen, K. <strong>Characterization of the human adenylyl cyclase gene family: cDNA, gene structure, and tissue distribution of the nine isoforms.</strong> J. Recept. Signal Transduct. Res. 22: 79-110, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12503609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12503609</a>] [<a href="https://doi.org/10.1081/rrs-120014589" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12503609">Ludwig and Seuwen, 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12503609" 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 database analysis and PCR of a human cDNA library, <a href="#18" class="mim-tip-reference" title="Ludwig, M.-G., Seuwen, K. <strong>Characterization of the human adenylyl cyclase gene family: cDNA, gene structure, and tissue distribution of the nine isoforms.</strong> J. Recept. Signal Transduct. Res. 22: 79-110, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12503609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12503609</a>] [<a href="https://doi.org/10.1081/rrs-120014589" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12503609">Ludwig and Seuwen (2002)</a> cloned full-length ADCY5. EST database analysis revealed 2 alternative polyadenylation sites. The deduced protein contains 1,261 amino acids. Semiquantitative RT-PCR detected high expression of ADCY5 in heart and testis, moderate expression in brain, prostate, ovary, small intestine, and colon, and low expression in lung and liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12503609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Mencacci, N. E., Erro, R., Wiethoff, S., Hersheson, J., Ryten, M., Balint, B., Ganos, C., Stamelou, M., Quinn, N., Houlden, H., Wood, N. W., Bhatia, K. P. <strong>ADCY5 mutations are another cause of benign hereditary chorea.</strong> Neurology 85: 80-88, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26085604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26085604</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26085604[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/10.1212/WNL.0000000000001720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26085604">Mencacci et al. (2015)</a> found expression of the ADCY5 gene in multiple human brain regions, with highest expression in the putamen and adult striatum. ADCY5 expression progressively increased in the striatum during embryonic development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26085604" 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="#18" class="mim-tip-reference" title="Ludwig, M.-G., Seuwen, K. <strong>Characterization of the human adenylyl cyclase gene family: cDNA, gene structure, and tissue distribution of the nine isoforms.</strong> J. Recept. Signal Transduct. Res. 22: 79-110, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12503609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12503609</a>] [<a href="https://doi.org/10.1081/rrs-120014589" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12503609">Ludwig and Seuwen (2002)</a> determined that the ADCY5 gene contains 21 exons and spans 167 kb. The first exon is 95 kb upstream of the clustered next 20 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12503609" 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 Southern blot analysis of somatic cell hybrid DNAs, <a href="#13" class="mim-tip-reference" title="Gaudin, C., Homcy, C. J., Ishikawa, Y. <strong>Mammalian adenylyl cyclase family members are randomly located on different chromosomes.</strong> Hum. Genet. 94: 527-529, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7959689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7959689</a>] [<a href="https://doi.org/10.1007/BF00211020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7959689">Gaudin et al. (1994)</a> mapped the ADCY5 gene to chromosome 3. Using isotopic in situ hybridization, <a href="#14" class="mim-tip-reference" title="Haber, N., Stengel, D., Defer, N., Roeckel, N., Mattei, M.-G., Hanoune, J. <strong>Chromosomal mapping of human adenylyl cyclase genes type III, type V and type VI.</strong> Hum. Genet. 94: 69-73, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8034296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8034296</a>] [<a href="https://doi.org/10.1007/BF02272844" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8034296">Haber et al. (1994)</a> mapped the ADCY5 gene to 3q13.2-q21. By fluorescence in situ hybridization, <a href="#10" class="mim-tip-reference" title="Edelhoff, S., Villacres, E. C., Storm, D. R., Disteche, C. M. <strong>Mapping of adenylyl cyclase genes type I, II, III, IV, V, and VI in mouse.</strong> Mammalian Genome 6: 111-113, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7766992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7766992</a>] [<a href="https://doi.org/10.1007/BF00303253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7766992">Edelhoff et al. (1995)</a> mapped the ADCY5 gene to human chromosome 3q13 and to mouse chromosome 16 in the B5 region. In both species, the gene maps close to GAP43 (<a href="/entry/162060">162060</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7959689+8034296+7766992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Stumpf, A. M. <strong>Personal Communication.</strong> Baltimore, Md. 12/08/2021."None>Stumpf (2021)</a> mapped the ADCY5 gene to chromosome 3q21.1 based on an alignment of the ADCY5 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF497517" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF497517</a>) with the genomic sequence (GRCh38).</p>
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<p><strong><em>Autosomal Dominant Dyskinesia with Orofacial Involvement</em></strong></p><p>
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In affected members of a large German family with autosomal dominant dyskinesia with orofacial involvement (DSKOD; <a href="/entry/606703">606703</a>), <a href="#8" class="mim-tip-reference" title="Chen, Y.-Z., Matsushita, M. M., Robertson, P., Rieder, M., Girirajan, S., Antonacci, F., Lipe, H., Eichler, E. E., Nickerson, D. A., Bird, T. D., Raskind, W. H. <strong>Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5.</strong> Arch. Neurol. 69: 630-635, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22782511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22782511</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22782511[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/10.1001/archneurol.2012.54" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22782511">Chen et al. (2012)</a> identified a heterozygous missense mutation in the ADCY5 gene (A726T; <a href="#0001">600293.0001</a>). The family had previously been reported by <a href="#3" class="mim-tip-reference" title="Bird, T. D., Hall, J. G. <strong>Additional information on familial essential (benign) chorea. (Letter)</strong> Clin. Genet. 14: 271-272, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/152174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">152174</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1978.tb02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="152174">Bird and Hall (1978)</a>. <a href="#6" class="mim-tip-reference" title="Chen, D.-H., Meneret, A., Friedman, J. R., Korvatska, O., Gad, A., Bonkowski, E. S., Stessman, H. A., Doummar, D., Mignot, C., Anheim, M., Bernes, S., Davis, M. Y., and 19 others. <strong>ADCY5-related dyskinesia: broader spectrum and genotype-phenotype correlations.</strong> Neurology 85: 2026-2035, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26537056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26537056</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26537056[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/10.1212/WNL.0000000000002058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26537056">Chen et al. (2015)</a> identified this same heterozygous mutation in a large American family with the disorder; the family had previously been reported by <a href="#2" class="mim-tip-reference" title="Bird, T. D., Carlson, C. B., Hall, J. G. <strong>Familial essential ('benign') chorea.</strong> J. Med. Genet. 13: 357-362, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1003446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1003446</a>] [<a href="https://doi.org/10.1136/jmg.13.5.357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1003446">Bird et al. (1976)</a> and <a href="#11" class="mim-tip-reference" title="Fernandez, M., Raskind, W., Matsushita, M., Wolff, J., Lipe, H., Bird, T. <strong>Hereditary benign chorea: clinical and genetic features of a distinct disease.</strong> Neurology 57: 106-110, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11445636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11445636</a>] [<a href="https://doi.org/10.1212/wnl.57.1.106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11445636">Fernandez et al. (2001)</a>. In vitro functional expression studies performed by <a href="#7" class="mim-tip-reference" title="Chen, Y.-Z., Friedman, J. R., Chen, D.-H., Chan, G. C.-K., Bloss, C. S., Hisama, F. M., Topol, S. E., Carson, A. R., Pham, P. H., Bonkowski, E. S., Scott, E. R., Lee, J. K., and 13 others. <strong>Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia.</strong> Ann. Neurol. 75: 542-549, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24700542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24700542</a>] [<a href="https://doi.org/10.1002/ana.24119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24700542">Chen et al. (2014)</a> showed that mutant A726T ADCY5 caused a significant increase in cAMP production in response to beta-adrenergic stimulation compared to wildtype, consistent with a gain of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26537056+11445636+1003446+22782511+24700542+152174" 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 2 unrelated teenaged girls of European ancestry with DSKOD, <a href="#7" class="mim-tip-reference" title="Chen, Y.-Z., Friedman, J. R., Chen, D.-H., Chan, G. C.-K., Bloss, C. S., Hisama, F. M., Topol, S. E., Carson, A. R., Pham, P. H., Bonkowski, E. S., Scott, E. R., Lee, J. K., and 13 others. <strong>Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia.</strong> Ann. Neurol. 75: 542-549, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24700542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24700542</a>] [<a href="https://doi.org/10.1002/ana.24119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24700542">Chen et al. (2014)</a> identified a de novo heterozygous mutation in the ADCY5 gene (R418W; <a href="#0002">600293.0002</a>). The mutations were found by whole-exome sequencing. In vitro functional expression studies showed that both mutant A726T and R418W ADCY5 caused a significant increase in cAMP production in response to beta-adrenergic stimulation compared to wildtype, consistent with a gain of function. One of the girls with a more severe phenotype also carried a de novo heterozygous N1882S variant in the DOCK3 gene (<a href="/entry/603123">603123</a>), which may have a role in neuronal activity and could have possibly contributed to the phenotype. In addition, sequence reads suggested that the girl with the less severe phenotype may have been somatic mosaic for the R418W mutation. <a href="#7" class="mim-tip-reference" title="Chen, Y.-Z., Friedman, J. R., Chen, D.-H., Chan, G. C.-K., Bloss, C. S., Hisama, F. M., Topol, S. E., Carson, A. R., Pham, P. H., Bonkowski, E. S., Scott, E. R., Lee, J. K., and 13 others. <strong>Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia.</strong> Ann. Neurol. 75: 542-549, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24700542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24700542</a>] [<a href="https://doi.org/10.1002/ana.24119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24700542">Chen et al. (2014)</a> postulated that these findings may have played a role in the phenotypic variability observed in the 2 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24700542" 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 French father and son with DSKOD, <a href="#5" class="mim-tip-reference" title="Carapito, R., Paul, N., Untrau, M., Le Gentil, M., Ott, L., Alsaleh, G., Jochem, P., Radosavljevic, M., Le Caignec, C., David, A., Damier, P., Isidor, B., Bahram, S. <strong>A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia.</strong> Mov. Disord. 30: 423-427, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25545163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25545163</a>] [<a href="https://doi.org/10.1002/mds.26115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25545163">Carapito et al. (2015)</a> identified a heterozygous splice site mutation in the ADCY5 gene (<a href="#0003">600293.0003</a>). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells had decreased ADCY5 mRNA levels, consistent with degradation of the mutant transcript, a loss of function, and haploinsufficiency. The patients had an early onset hyperkinetic movement disorder with dystonia and chorea, but no facial myokymia, thus expanding the phenotype. The findings also suggested that haploinsufficiency of ADCY5 is pathogenic, although a gain-of-function effect could not be excluded. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25545163" 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 14-year-old boy (L-3482) adopted from Southeastern Europe with DSKOD, <a href="#25" class="mim-tip-reference" title="Westenberger, A., Max, C., Bruggemann, N., Domingo, A., Grutz, K., Pawlack, H., Weissbach, A., Kuhn, A. A., Spiegler, J., Lang, A. E., Sperner, J., Fung, V. S. C., Schallner, J., Gillessen-Kaesbach, G., Munchau, A., Klein, C. <strong>Alternating hemiplegia of childhood as a new presentation of adenylate cyclase 5-mutation-associated disease: a report of two cases.</strong> J. Pediat. 181: 306-308, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27931826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27931826</a>] [<a href="https://doi.org/10.1016/j.jpeds.2016.10.079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27931826">Westenberger et al. (2017)</a> identified a heterozygous missense mutation in the ADCY5 gene (D1015E; <a href="#0004">600293.0004</a>). The mutation, which was found by direct sequencing, was not present in the ExAC database. Functional studies of the variant and studies of patient cells were not performed. In addition to a hyperkinetic movement disorder, the patient had paroxysmal limb weakness reminiscent of alternating hemiplegia of childhood. The report further expanded the phenotype associated with ADCY5 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27931826" 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 21-year-old woman with DSKOD, <a href="#9" class="mim-tip-reference" title="Dean, M., Messiaen, L., Cooper, G. M., Amaral, M. D., Rashid, S., Korf, B. R., Standaert, D. G. <strong>Child neurology: spastic paraparesis and dystonia with a novel ADCY5 mutation.</strong> Neurology 93: 510-514, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31501304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31501304</a>] [<a href="https://doi.org/10.1212/WNL.0000000000008089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31501304">Dean et al. (2019)</a> identified a de novo heterozygous missense mutation in the ADCY5 gene (Y233H; <a href="#0005">600293.0005</a>) affecting a conserved residue in the M1 domain. The mutation, which was found by whole-genome sequencing, was not present in the ExAC or 1000 Genomes Project databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to be likely pathogenic according to ACMG criteria. In addition to dyskinesia and dystonia, the patient had spastic paraplegia and mild distal sensory impairment. <a href="#9" class="mim-tip-reference" title="Dean, M., Messiaen, L., Cooper, G. M., Amaral, M. D., Rashid, S., Korf, B. R., Standaert, D. G. <strong>Child neurology: spastic paraparesis and dystonia with a novel ADCY5 mutation.</strong> Neurology 93: 510-514, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31501304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31501304</a>] [<a href="https://doi.org/10.1212/WNL.0000000000008089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31501304">Dean et al. (2019)</a> noted that a heterozygous missense variant (E908K) identified by <a href="#24" class="mim-tip-reference" title="Waalkens, A. J. E., Vansenne, F., van der Hout, A. H., Zutt, R., Mourmans, J., Tolosa, E., de Koning, T. J., Tijssen, M. A. J. <strong>Expanding the ADCY5 phenotype toward spastic paraparesis: a mutation in the M2 domain.</strong> Neurol. Genet. 4: e214, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29473048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29473048</a>] [<a href="https://doi.org/10.1212/NXG.0000000000000214" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29473048">Waalkens et al. (2018)</a> in a patient with spastic paraparesis and mild dystonia affected the M2 domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29473048+31501304" 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 an 18-year-old man (INDF10_3) of Indian origin with DSKOD, <a href="#17" class="mim-tip-reference" title="Kumar, K. R., Davis, R. L., Tchan, M. C., Wali, G. M., Mahant, N., Ng, K., Kotschet, K., Siow, S.-F., Gu, J., Walls, Z., Kang, C., Wali, G., and 16 others. <strong>Whole genome sequencing for the genetic diagnosis of heterogenous dystonia phenotypes.</strong> Parkinsonism Relat. Disord. 69: 111-118, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31731261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31731261</a>] [<a href="https://doi.org/10.1016/j.parkreldis.2019.11.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31731261">Kumar et al. (2019)</a> identified a de novo heterozygous missense mutation in the ADCY5 gene (M1029K; <a href="#0006">600293.0006</a>). The mutation was found by whole-genome sequencing and confirmed by Sanger sequencing and filtered against control databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to be pathogenic according to ACMG criteria. The patient had myoclonic dystonia, congenital encephalopathy, and daily paroxysmal ballismus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31731261" 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>Autosomal Recessive Dyskinesia with Orofacial Involvement</em></strong></p><p>
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In 2 sibs with autosomal recessive dyskinesia with orofacial involvement (DSKOR; <a href="/entry/619647">619647</a>), <a href="#1" class="mim-tip-reference" title="Barrett, M. J., Williams, E. S., Chambers, C., Dhamija, R. <strong>Autosomal recessive inheritance of ADCY5-related generalized dystonia and myoclonus.</strong> Neurol. Genet. 3: 193, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28971144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28971144</a>] [<a href="https://doi.org/10.1212/NXG.0000000000000193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28971144">Barrett et al. (2017)</a> identified compound heterozygous mutations in the ADCY5 gene (<a href="#0007">600293.0007</a> and <a href="#0008">600293.0008</a>). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed. The parents, who were heterozygous carriers of 1 of the mutations, were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28971144" 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 6 sibs, born of consanguineous Arab parents, with DSKOR, <a href="#4" class="mim-tip-reference" title="Bohlega, S. A., Abou-Al-Shaar, H., AlDakheel, A., Alajlan, H., Bohlega, B. S., Meyer, B. F., Monies, D., Cupler, E. J.,, Al-Saif, A. M. <strong>Autosomal recessive ADCY5-related dystonia and myoclonus: expanding the genetic spectrum of ADCY5-related movement disorders.</strong> Parkinsonism Relat. Disord. 64: 145-149, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30975617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30975617</a>] [<a href="https://doi.org/10.1016/j.parkreldis.2019.02.039" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30975617">Bohlega et al. (2019)</a> identified a homozygous missense mutation in the ADCY5 gene (D588N; <a href="#0009">600293.0009</a>). The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. The parents, who were heterozygous carriers of the mutation, were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30975617" 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>Neurodevelopmental Disorder with Hyperkinetic Movements and Dyskinesia</em></strong></p><p>
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In 2 sibs, born of unrelated Japanese parents, with neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD; <a href="/entry/619651">619651</a>), <a href="#21" class="mim-tip-reference" title="Okamoto, N., Miya, F., Kitai, Y., Tsunoda, T., Kato, M., Saitoh, S., Kanemura, Y., Kosaki, K. <strong>Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability.</strong> Neurol. Sci. 42: 2975-2978, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33704598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33704598</a>] [<a href="https://doi.org/10.1007/s10072-021-05152-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33704598">Okamoto et al. (2021)</a> identified a homozygous missense mutation affecting the C terminus of the ADCY5 gene (R1238W; <a href="#0010">600293.0010</a>). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. At 3 and 1.5 years of age, the patients had severe intellectual disability, axial hypotonia with inability to control the heard, poor eye contact, and dystonic posturing. The parents, who were heterozygous carriers of the mutation, were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33704598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 sibs, born of consanguineous Egyptian parents, with NEDHYD, <a href="#15" class="mim-tip-reference" title="Kaiyrzhanov, R., Zaki, M. S., Maroofian, R., Dominik, N., Rad, A., Vona, B., Houlden, H. <strong>A novel homozygous ADCY5 variant is associated with a neurodevelopmental disorder and movement abnormalities.</strong> Mov. Disord. Clin. Pract. 8: 1140-1143, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34631954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34631954</a>] [<a href="https://doi.org/10.1002/mdc3.13310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34631954">Kaiyrzhanov et al. (2021)</a> identified a homozygous splice site mutation in the ADCY5 gene (<a href="#0011">600293.0011</a>). The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro minigene constructs confirmed that the mutation resulted in splicing defects of ADCY5. Functional studies of the variant were not performed, but it was predicted to result in a loss of function. The patients had a severe form of the disorder with poor overall growth, various involuntary movements, severe intellectual disability, and inability to walk or talk. One had cardiomyopathy and died at 4.5 years of age. The carrier parents were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34631954" 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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For discussion of a possible association between variation in the ADCY5 gene and fasting plasma glucose, birth weight, and 2-hour plasma glucose levels as quantitative traits, see <a href="/entry/613460">613460</a>.</p>
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<p><a href="#16" class="mim-tip-reference" title="Kim, K.-S., Lee, K.-W., Lee, K.-W., Im, J.-Y., Yoo, J. Y., Kim, S.-W., Lee, J.-K., Nestler, E. J., Han, P.-L. <strong>Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action.</strong> Proc. Nat. Acad. Sci. 103: 3908-3913, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16537460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16537460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16537460[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.0508812103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16537460">Kim et al. (2006)</a> found that Adcy5-null mice had decreased behavioral responses to morphine, including locomotor activation, analgesia, tolerance, reward, physical dependence, and withdrawal symptoms, compared to wildtype mice. Adcy5-null mice also showed attenuated responses to selective mu (<a href="/entry/600018">600018</a>) and delta (<a href="/entry/165195">165195</a>) opioid receptor agonists, whereas responses to kappa (<a href="/entry/165196">165196</a>) opioid receptor agonists were similar to wildtype mice. The results indicated that ADCY5 is an important component of mu- and delta-opioid receptor signal transduction mechanisms in the striatum and provided further support for the importance of the cAMP pathway as a mediator of opioid action. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16537460" 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">rs796065306 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796065306;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs796065306" 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=rs796065306" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of a large multigenerational German family with autosomal dominant dyskinesia with orofacial involvement (DSKOD; <a href="/entry/606703">606703</a>), previously reported by <a href="#3" class="mim-tip-reference" title="Bird, T. D., Hall, J. G. <strong>Additional information on familial essential (benign) chorea. (Letter)</strong> Clin. Genet. 14: 271-272, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/152174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">152174</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1978.tb02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="152174">Bird and Hall (1978)</a> and <a href="#12" class="mim-tip-reference" title="Fernandez, M., Raskind, W., Wolff, J., Matsushita, M., Yuen, E., Graf, W., Lipe, H., Bird, T. <strong>Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder.</strong> Ann. Neurol. 49: 486-492, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11310626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11310626</a>]" pmid="11310626">Fernandez et al. (2001)</a>, <a href="#8" class="mim-tip-reference" title="Chen, Y.-Z., Matsushita, M. M., Robertson, P., Rieder, M., Girirajan, S., Antonacci, F., Lipe, H., Eichler, E. E., Nickerson, D. A., Bird, T. D., Raskind, W. H. <strong>Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5.</strong> Arch. Neurol. 69: 630-635, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22782511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22782511</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22782511[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/10.1001/archneurol.2012.54" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22782511">Chen et al. (2012)</a> identified a heterozygous c.2176G-A transition in exon 10 of the ADCY5 gene, resulting in an ala726-to-thr (A726T) substitution at a highly conserved residue between the first intracellular cyclase homology domain and the second membrane-spanning domain. The mutation was identified by exome sequencing of 1 affected individual and was not found in 3,510 control exomes. <a href="#8" class="mim-tip-reference" title="Chen, Y.-Z., Matsushita, M. M., Robertson, P., Rieder, M., Girirajan, S., Antonacci, F., Lipe, H., Eichler, E. E., Nickerson, D. A., Bird, T. D., Raskind, W. H. <strong>Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5.</strong> Arch. Neurol. 69: 630-635, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22782511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22782511</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22782511[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/10.1001/archneurol.2012.54" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22782511">Chen et al. (2012)</a> noted that Adcy5-null mice develop a movement disorder that is worsened by stress (<a href="#16" class="mim-tip-reference" title="Kim, K.-S., Lee, K.-W., Lee, K.-W., Im, J.-Y., Yoo, J. Y., Kim, S.-W., Lee, J.-K., Nestler, E. J., Han, P.-L. <strong>Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action.</strong> Proc. Nat. Acad. Sci. 103: 3908-3913, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16537460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16537460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16537460[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.0508812103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16537460">Kim et al., 2006</a>), supporting the pathogenicity of the A726T mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22782511+11310626+16537460+152174" 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 vitro functional expression studies performed by <a href="#7" class="mim-tip-reference" title="Chen, Y.-Z., Friedman, J. R., Chen, D.-H., Chan, G. C.-K., Bloss, C. S., Hisama, F. M., Topol, S. E., Carson, A. R., Pham, P. H., Bonkowski, E. S., Scott, E. R., Lee, J. K., and 13 others. <strong>Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia.</strong> Ann. Neurol. 75: 542-549, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24700542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24700542</a>] [<a href="https://doi.org/10.1002/ana.24119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24700542">Chen et al. (2014)</a> showed that mutant A726T ADCY5 caused a significant increase in cAMP production in response to beta-adrenergic stimulation compared to wildtype, consistent with a gain of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24700542" 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 affected members of a large 5-generation family (EHC) with DSKOD, previously reported by <a href="#2" class="mim-tip-reference" title="Bird, T. D., Carlson, C. B., Hall, J. G. <strong>Familial essential ('benign') chorea.</strong> J. Med. Genet. 13: 357-362, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1003446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1003446</a>] [<a href="https://doi.org/10.1136/jmg.13.5.357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1003446">Bird et al. (1976)</a> and <a href="#11" class="mim-tip-reference" title="Fernandez, M., Raskind, W., Matsushita, M., Wolff, J., Lipe, H., Bird, T. <strong>Hereditary benign chorea: clinical and genetic features of a distinct disease.</strong> Neurology 57: 106-110, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11445636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11445636</a>] [<a href="https://doi.org/10.1212/wnl.57.1.106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11445636">Fernandez et al. (2001)</a>, <a href="#6" class="mim-tip-reference" title="Chen, D.-H., Meneret, A., Friedman, J. R., Korvatska, O., Gad, A., Bonkowski, E. S., Stessman, H. A., Doummar, D., Mignot, C., Anheim, M., Bernes, S., Davis, M. Y., and 19 others. <strong>ADCY5-related dyskinesia: broader spectrum and genotype-phenotype correlations.</strong> Neurology 85: 2026-2035, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26537056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26537056</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26537056[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/10.1212/WNL.0000000000002058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26537056">Chen et al. (2015)</a> identified a heterozygous A726T mutation in the ADCY5 gene. The mutation, which was found by direct Sanger sequencing, segregated completely with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. Haplotype analysis showed that the German family reported by <a href="#8" class="mim-tip-reference" title="Chen, Y.-Z., Matsushita, M. M., Robertson, P., Rieder, M., Girirajan, S., Antonacci, F., Lipe, H., Eichler, E. E., Nickerson, D. A., Bird, T. D., Raskind, W. H. <strong>Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5.</strong> Arch. Neurol. 69: 630-635, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22782511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22782511</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22782511[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/10.1001/archneurol.2012.54" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22782511">Chen et al. (2012)</a> and family EHC, from the US, did not share a common haplotype; the mutations arose independently. The EHC family had originally been diagnosed with benign hereditary chorea (see <a href="/entry/118700">118700</a>). <a href="#6" class="mim-tip-reference" title="Chen, D.-H., Meneret, A., Friedman, J. R., Korvatska, O., Gad, A., Bonkowski, E. S., Stessman, H. A., Doummar, D., Mignot, C., Anheim, M., Bernes, S., Davis, M. Y., and 19 others. <strong>ADCY5-related dyskinesia: broader spectrum and genotype-phenotype correlations.</strong> Neurology 85: 2026-2035, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26537056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26537056</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26537056[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/10.1212/WNL.0000000000002058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26537056">Chen et al. (2015)</a> noted that the A726T mutation is associated with a relatively mild phenotype. <a href="#11" class="mim-tip-reference" title="Fernandez, M., Raskind, W., Matsushita, M., Wolff, J., Lipe, H., Bird, T. <strong>Hereditary benign chorea: clinical and genetic features of a distinct disease.</strong> Neurology 57: 106-110, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11445636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11445636</a>] [<a href="https://doi.org/10.1212/wnl.57.1.106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11445636">Fernandez et al. (2001)</a> stated that the phenotype in this family was nonprogressive in adulthood and that dementia was not observed, although some patients had educational or behavioral difficulties, possibly resulting from social isolation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26537056+11445636+1003446+22782511" 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">rs864309483 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs864309483;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs864309483" 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=rs864309483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 unrelated teenaged girls of European ancestry with autosomal dominant dyskinesia with orofacial involvement (DSKOD; <a href="/entry/606703">606703</a>), <a href="#7" class="mim-tip-reference" title="Chen, Y.-Z., Friedman, J. R., Chen, D.-H., Chan, G. C.-K., Bloss, C. S., Hisama, F. M., Topol, S. E., Carson, A. R., Pham, P. H., Bonkowski, E. S., Scott, E. R., Lee, J. K., and 13 others. <strong>Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia.</strong> Ann. Neurol. 75: 542-549, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24700542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24700542</a>] [<a href="https://doi.org/10.1002/ana.24119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24700542">Chen et al. (2014)</a> identified a de novo heterozygous c.1252C-T transition in the ADCY5 gene, resulting in an arg418-to-trp (R418W) substitution at a conserved residue in the sixth helical segment of the first transmembrane domain. The mutations were found by whole-exome sequencing. In vitro functional expression studies showed that mutant R418W ADCY5 caused a significant increase in cAMP production in response to beta-adrenergic stimulation compared to wildtype, consistent with a gain of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24700542" 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 2 unrelated patients of UK and Pakistani ancestry with DSKOD, <a href="#19" class="mim-tip-reference" title="Mencacci, N. E., Erro, R., Wiethoff, S., Hersheson, J., Ryten, M., Balint, B., Ganos, C., Stamelou, M., Quinn, N., Houlden, H., Wood, N. W., Bhatia, K. P. <strong>ADCY5 mutations are another cause of benign hereditary chorea.</strong> Neurology 85: 80-88, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26085604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26085604</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26085604[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/10.1212/WNL.0000000000001720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26085604">Mencacci et al. (2015)</a> identified a heterozygous R418W mutation. The mutation was found by exome sequencing and confirmed by Sanger sequencing. In the first family, the mutation was inherited from the patient's mildly affected father who was somatic mosaic for the mutation. R418W occurred de novo in the proband from family 2. Functional studies of the variant were not performed. The probands had typical features of the disorder with onset of progressive and severe choreodystonic dyskinesias with orofacial involvement in the first years of life. The hyperkinetic movements were exacerbated by action, excitement, stress, and fatigue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26085604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Shetty, K., Sarma, A. S., Devan, M., Dalal, A., Dash, G. K., Jannabhatla, A., Patil, S. J. <strong>Recurrent ADCY5 mutation in mosaic form with nocturnal paroxysmal dyskinesias and video electroencephalography documentation of dramatic response to caffeine treatment. (Letter)</strong> J. Mov. Disord. 13: 238-240, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32713175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32713175</a>] [<a href="https://doi.org/10.14802/jmd.20014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32713175">Shetty et al. (2020)</a> reported an Indian man with DKSOD who had the R418W mutation (c.1252C-T, NM_183357.2) in mosaic state with low mutant read depth. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was absent in the parents. The patient had paroxysmal involuntary movements during sleep. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32713175" 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">rs797045002 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797045002;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs797045002" 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=rs797045002" 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=RCV000202586 OR RCV002298522" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000202586, RCV002298522" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000202586...</a>
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<p>In a French father and son with autosomal dominant dyskinesia with facial involvement (DSKOD; <a href="/entry/606703">606703</a>), <a href="#5" class="mim-tip-reference" title="Carapito, R., Paul, N., Untrau, M., Le Gentil, M., Ott, L., Alsaleh, G., Jochem, P., Radosavljevic, M., Le Caignec, C., David, A., Damier, P., Isidor, B., Bahram, S. <strong>A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia.</strong> Mov. Disord. 30: 423-427, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25545163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25545163</a>] [<a href="https://doi.org/10.1002/mds.26115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25545163">Carapito et al. (2015)</a> identified a heterozygous G-to-A transition (c.2088+1G-A) in intron 8 of the ADCY5 gene, resulting in a splicing defect. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells had decreased ADCY5 mRNA levels, consistent with degradation of the mutant transcript, a loss of function, and haploinsufficiency. The patients had an early-onset hyperkinetic movement disorder with dystonia and chorea, but no facial myokymia, thus expanding the phenotype. The findings also suggested that haploinsufficiency of ADCY5 is pathogenic, although the authors could not rule out a gain-of-function effect via production of a long alternatively spliced mRNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25545163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Meneret, A., Gras, D., McGovern, E., Roze, E. <strong>Caffeine and the dyskinesia related to mutations in the ADCY5 gene.</strong> Ann. Intern. Med. 171: 439, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31181574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31181574</a>] [<a href="https://doi.org/10.7326/L19-0038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31181574">Meneret et al. (2019)</a> reported an 11-year-old boy with DSKOD who was mosaic for the c.2088+1G-A mutation. These authors postulated a gain-of-function effect, although no functional studies of the variant or studies of patient cells were performed. The patient had a remarkable favorable response to caffeinated coffee, which resulted in near complete resolution of the dyskinetic episodes. <a href="#20" class="mim-tip-reference" title="Meneret, A., Gras, D., McGovern, E., Roze, E. <strong>Caffeine and the dyskinesia related to mutations in the ADCY5 gene.</strong> Ann. Intern. Med. 171: 439, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31181574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31181574</a>] [<a href="https://doi.org/10.7326/L19-0038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31181574">Meneret et al. (2019)</a> postulated that the caffeine antagonized adenosine A2A receptors, which would inhibit the ADCY5 enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31181574" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT</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">rs1007363034 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1007363034;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1007363034" 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=rs1007363034" 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=RCV001789712" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001789712" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001789712</a>
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<p>In a 14-year-old boy (L-3482) adopted from Southeastern Europe with autosomal dominant dyskinesia with orofacial involvement (DSKOD; <a href="/entry/606703">606703</a>), <a href="#25" class="mim-tip-reference" title="Westenberger, A., Max, C., Bruggemann, N., Domingo, A., Grutz, K., Pawlack, H., Weissbach, A., Kuhn, A. A., Spiegler, J., Lang, A. E., Sperner, J., Fung, V. S. C., Schallner, J., Gillessen-Kaesbach, G., Munchau, A., Klein, C. <strong>Alternating hemiplegia of childhood as a new presentation of adenylate cyclase 5-mutation-associated disease: a report of two cases.</strong> J. Pediat. 181: 306-308, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27931826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27931826</a>] [<a href="https://doi.org/10.1016/j.jpeds.2016.10.079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27931826">Westenberger et al. (2017)</a> identified a heterozygous c.3045C-A transition in the ADCY5 gene, resulting in an asp1015-to-glu (D1015E) substitution at a conserved residue in the second cytoplasmic domain that forms the catalytic pocket. The mutation, which was found by direct sequencing, was not present in the ExAC database. Functional studies of the variant and studies of patient cells were not performed. In addition to a hyperkinetic movement disorder, the patient had paroxysmal limb weakness reminiscent of alternating hemiplegia of childhood. The report further expanded the phenotype associated with ADCY5 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27931826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT</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">rs2107658582 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2107658582;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2107658582" 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=rs2107658582" 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=RCV001789713" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001789713" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001789713</a>
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<p>In a 21-year-old woman with hyperkinetic movement disorder with autosomal dominant dyskinesia with orofacial involvement (DSKOD; <a href="/entry/606703">606703</a>), <a href="#9" class="mim-tip-reference" title="Dean, M., Messiaen, L., Cooper, G. M., Amaral, M. D., Rashid, S., Korf, B. R., Standaert, D. G. <strong>Child neurology: spastic paraparesis and dystonia with a novel ADCY5 mutation.</strong> Neurology 93: 510-514, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31501304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31501304</a>] [<a href="https://doi.org/10.1212/WNL.0000000000008089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31501304">Dean et al. (2019)</a> identified a de novo heterozygous c.697T-C transition in exon 1 of in the ADCY5 gene, resulting in a tyr233-to-his (Y233H) substitution at a conserved residue in the M1 domain. The mutation, which was found by whole-genome sequencing, was not present in the ExAC or 1000 Genomes Project databases. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to be likely pathogenic according to ACMG criteria. In addition to dyskinesia and dystonia, the patient had spastic paraplegia and mild distal sensory impairment, further expanding the phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31501304" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT</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">rs864309484 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs864309484;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs864309484" 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=rs864309484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an 18-year-old man (INDF10_3) of Indian origin with autosomal dominant dyskinesia with orofacial involvement (DSKOD; <a href="/entry/606703">606703</a>), <a href="#17" class="mim-tip-reference" title="Kumar, K. R., Davis, R. L., Tchan, M. C., Wali, G. M., Mahant, N., Ng, K., Kotschet, K., Siow, S.-F., Gu, J., Walls, Z., Kang, C., Wali, G., and 16 others. <strong>Whole genome sequencing for the genetic diagnosis of heterogenous dystonia phenotypes.</strong> Parkinsonism Relat. Disord. 69: 111-118, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31731261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31731261</a>] [<a href="https://doi.org/10.1016/j.parkreldis.2019.11.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31731261">Kumar et al. (2019)</a> identified a de novo heterozygous c.3086T-A transversion (c.3086T-A, NM_183357.2) in exon 18 of the ADCY5 gene, resulting in a met1029-to-lys (M1029K) substitution. The mutation was found by whole-genome sequencing and confirmed by Sanger sequencing and filtered against control databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to be pathogenic according to ACMG criteria. The patient had myoclonic dystonia, congenital encephalopathy, and daily paroxysmal ballismus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31731261" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL RECESSIVE</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> rs1365372289 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1365372289;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/rs1365372289?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=rs1365372289" 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=rs1365372289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 sibs with autosomal recessive dyskinesia with orofacial involvement (DSKOR; <a href="/entry/619647">619647</a>), <a href="#1" class="mim-tip-reference" title="Barrett, M. J., Williams, E. S., Chambers, C., Dhamija, R. <strong>Autosomal recessive inheritance of ADCY5-related generalized dystonia and myoclonus.</strong> Neurol. Genet. 3: 193, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28971144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28971144</a>] [<a href="https://doi.org/10.1212/NXG.0000000000000193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28971144">Barrett et al. (2017)</a> identified compound heterozygous mutations in the ADCY5 gene: a c.3037C-T transition (c.3037C-T, NM_183357), resulting in an arg1013-to-cys (R1013C) substitution at a conserved residue, and a 20-bp deletion (c.409_428del20; <a href="#0008">600293.0008</a>), predicted to result in a frameshift and premature termination (Gly137CysfsTer184). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. R1013C was not present in the ExAC database. Functional studies of the variants and studies of patient cells were not performed. The parents, who were each a heterozygous carrier of 1 of the mutations, were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28971144" 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>.0008 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL RECESSIVE</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">rs1553751262 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553751262;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1553751262" 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=rs1553751262" 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=RCV000624020 OR RCV001789709" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000624020, RCV001789709" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000624020...</a>
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<p>For discussion of the 20-bp deletion (c.409_428del20, NM_183357) in the ADCY5 gene, predicted to result in a frameshift and premature termination (Gly137CysfsTer184), that was found in compound heterozygous state in 2 sibs with autosomal recessive dyskinesia with orofacial involvement (DSKOR; <a href="/entry/619647">619647</a>) by <a href="#1" class="mim-tip-reference" title="Barrett, M. J., Williams, E. S., Chambers, C., Dhamija, R. <strong>Autosomal recessive inheritance of ADCY5-related generalized dystonia and myoclonus.</strong> Neurol. Genet. 3: 193, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28971144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28971144</a>] [<a href="https://doi.org/10.1212/NXG.0000000000000193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28971144">Barrett et al. (2017)</a>, see <a href="#0007">600293.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28971144" 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">rs2108390731 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2108390731;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2108390731" 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=rs2108390731" 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=RCV001789714 OR RCV004699475" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001789714, RCV004699475" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001789714...</a>
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<p>In 6 sibs, born of consanguineous Arab parents, with 2 sibs with autosomal recessive dyskinesia with orofacial involvement (DSKOR; <a href="/entry/619647">619647</a>), <a href="#4" class="mim-tip-reference" title="Bohlega, S. A., Abou-Al-Shaar, H., AlDakheel, A., Alajlan, H., Bohlega, B. S., Meyer, B. F., Monies, D., Cupler, E. J.,, Al-Saif, A. M. <strong>Autosomal recessive ADCY5-related dystonia and myoclonus: expanding the genetic spectrum of ADCY5-related movement disorders.</strong> Parkinsonism Relat. Disord. 64: 145-149, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30975617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30975617</a>] [<a href="https://doi.org/10.1016/j.parkreldis.2019.02.039" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30975617">Bohlega et al. (2019)</a> identified a homozygous c.1762G-A transition in exon 6 of the ADCY5 gene, resulting in an asp588-to-asn (D588N) substitution at a highly conserved residue. The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. The parents, who were heterozygous carriers of the mutation, were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30975617" 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>.0010 NEURODEVELOPMENTAL DISORDER WITH HYPERKINETIC MOVEMENTS AND DYSKINESIA</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">rs2108148749 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2108148749;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2108148749" 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=rs2108148749" 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=RCV001789715" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001789715" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001789715</a>
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<p>In 2 sibs, born of unrelated Japanese parents, with neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD; <a href="/entry/619651">619651</a>), <a href="#21" class="mim-tip-reference" title="Okamoto, N., Miya, F., Kitai, Y., Tsunoda, T., Kato, M., Saitoh, S., Kanemura, Y., Kosaki, K. <strong>Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability.</strong> Neurol. Sci. 42: 2975-2978, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33704598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33704598</a>] [<a href="https://doi.org/10.1007/s10072-021-05152-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33704598">Okamoto et al. (2021)</a> identified a homozygous c.3712C-T transition (c.3712C-T, NM_183357.2) in exon 21 of the ADCY5 gene, resulting in an arg1238-to-trp (R1238W) substitution at a highly conserved residue in the C terminus. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. The variant was not present in public databases. Functional studies of the variant and studies of patient cells were not performed. At 3 and 1.5 years of age, the patients had severe intellectual disability, axial hypotonia with inability to control the heard, poor eye contact, and dystonic posturing. The parents, who were heterozygous carriers of the mutation, were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33704598" 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>.0011 NEURODEVELOPMENTAL DISORDER WITH HYPERKINETIC MOVEMENTS AND DYSKINESIA</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">rs2108384208 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2108384208;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2108384208" 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=rs2108384208" 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=RCV001789716" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001789716" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001789716</a>
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<p>In 3 sibs, born of consanguineous Egyptian parents, with neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD; <a href="/entry/619651">619651</a>), <a href="#15" class="mim-tip-reference" title="Kaiyrzhanov, R., Zaki, M. S., Maroofian, R., Dominik, N., Rad, A., Vona, B., Houlden, H. <strong>A novel homozygous ADCY5 variant is associated with a neurodevelopmental disorder and movement abnormalities.</strong> Mov. Disord. Clin. Pract. 8: 1140-1143, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34631954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34631954</a>] [<a href="https://doi.org/10.1002/mdc3.13310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34631954">Kaiyrzhanov et al. (2021)</a> identified a homozygous G-to-T transversion (c.897+1G-T, NM_001199642.1) in intron 7 of the ADCY5 gene, predicted to result in a splicing defect. The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro minigene constructs confirmed that the mutation resulted in splicing defects of ADCY5. Functional studies of the variant were not performed, but it was predicted to result in a loss of function. The patients had a severe form of the disorder with poor overall growth, various involuntary movements, severe intellectual disability, and inability to walk or talk. One had cardiomyopathy and died at 4.5 years of age. The carrier parents were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34631954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Barrett, M. J., Williams, E. S., Chambers, C., Dhamija, R.
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<strong>Autosomal recessive inheritance of ADCY5-related generalized dystonia and myoclonus.</strong>
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Neurol. Genet. 3: 193, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28971144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28971144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28971144" 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/NXG.0000000000000193" target="_blank">Full Text</a>]
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Bird, T. D., Carlson, C. B., Hall, J. G.
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<strong>Familial essential ('benign') chorea.</strong>
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J. Med. Genet. 13: 357-362, 1976.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1003446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1003446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1003446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.13.5.357" target="_blank">Full Text</a>]
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Bird, T. D., Hall, J. G.
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<strong>Additional information on familial essential (benign) chorea. (Letter)</strong>
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Clin. Genet. 14: 271-272, 1978.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/152174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">152174</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=152174" 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/10.1111/j.1399-0004.1978.tb02146.x" target="_blank">Full Text</a>]
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Bohlega, S. A., Abou-Al-Shaar, H., AlDakheel, A., Alajlan, H., Bohlega, B. S., Meyer, B. F., Monies, D., Cupler, E. J.,, Al-Saif, A. M.
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<strong>Autosomal recessive ADCY5-related dystonia and myoclonus: expanding the genetic spectrum of ADCY5-related movement disorders.</strong>
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Parkinsonism Relat. Disord. 64: 145-149, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30975617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30975617</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30975617" 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.24119" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archneurol.2012.54" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/WNL.0000000000008089" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33704598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33704598</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33704598" 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/s10072-021-05152-y" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Shetty2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shetty, K., Sarma, A. S., Devan, M., Dalal, A., Dash, G. K., Jannabhatla, A., Patil, S. J.
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|
<strong>Recurrent ADCY5 mutation in mosaic form with nocturnal paroxysmal dyskinesias and video electroencephalography documentation of dramatic response to caffeine treatment. (Letter)</strong>
|
|
J. Mov. Disord. 13: 238-240, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32713175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32713175</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32713175" 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/10.14802/jmd.20014" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="23" class="mim-anchor"></a>
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<a id="Stumpf2021" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 12/08/2021.
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</p>
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</div>
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</li>
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<li>
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<a id="24" class="mim-anchor"></a>
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<a id="Waalkens2018" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Waalkens, A. J. E., Vansenne, F., van der Hout, A. H., Zutt, R., Mourmans, J., Tolosa, E., de Koning, T. J., Tijssen, M. A. J.
|
|
<strong>Expanding the ADCY5 phenotype toward spastic paraparesis: a mutation in the M2 domain.</strong>
|
|
Neurol. Genet. 4: e214, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29473048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29473048</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29473048" 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/NXG.0000000000000214" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="25" class="mim-anchor"></a>
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<a id="Westenberger2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Westenberger, A., Max, C., Bruggemann, N., Domingo, A., Grutz, K., Pawlack, H., Weissbach, A., Kuhn, A. A., Spiegler, J., Lang, A. E., Sperner, J., Fung, V. S. C., Schallner, J., Gillessen-Kaesbach, G., Munchau, A., Klein, C.
|
|
<strong>Alternating hemiplegia of childhood as a new presentation of adenylate cyclase 5-mutation-associated disease: a report of two cases.</strong>
|
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J. Pediat. 181: 306-308, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27931826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27931826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27931826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.jpeds.2016.10.079" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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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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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 06/02/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 01/12/2022<br>Anne M. Stumpf - updated : 12/08/2021<br>Cassandra L. Kniffin - updated : 12/07/2021<br>Cassandra L. Kniffin - updated : 4/10/2014<br>Cassandra L. Kniffin - updated : 8/20/2012<br>Cassandra L. Kniffin - updated : 7/16/2007<br>Patricia A. Hartz - updated : 10/11/2006
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 1/9/1995
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/02/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/11/2022<br>carol : 06/04/2022<br>carol : 06/02/2022<br>alopez : 01/14/2022<br>ckniffin : 01/12/2022<br>carol : 12/10/2021<br>alopez : 12/09/2021<br>carol : 12/09/2021<br>alopez : 12/08/2021<br>ckniffin : 12/07/2021<br>carol : 06/05/2017<br>mcolton : 08/07/2014<br>carol : 4/11/2014<br>mcolton : 4/11/2014<br>ckniffin : 4/10/2014<br>carol : 8/20/2012<br>carol : 8/20/2012<br>ckniffin : 8/20/2012<br>alopez : 6/24/2010<br>alopez : 6/22/2010<br>alopez : 6/22/2010<br>terry : 6/18/2010<br>wwang : 7/31/2007<br>ckniffin : 7/16/2007<br>carol : 10/12/2006<br>terry : 10/11/2006<br>mark : 4/11/1995<br>mark : 4/10/1995<br>terry : 1/30/1995<br>carol : 1/9/1995
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 600293
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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|
|
ADENYLATE CYCLASE 5; ADCY5
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
ADENYLYL CYCLASE 5
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: ADCY5</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 3q21.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 3:123,282,296-123,449,090 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
|
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<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
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<tr>
|
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<td rowspan="3">
|
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<span class="mim-font">
|
|
3q21.1
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Dyskinesia with orofacial involvement, autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
606703
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
|
<span class="mim-font">
|
|
Dyskinesia with orofacial involvement, autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619647
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
|
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</tr>
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|
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|
|
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Neurodevelopmental disorder with hyperkinetic movements and dyskinesia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619651
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
|
|
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>ADCY5 belongs to the adenylate cyclase (EC 4.6.1.1) family of enzymes responsible for the synthesis of cAMP (Ludwig and Seuwen, 2002). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By database analysis and PCR of a human cDNA library, Ludwig and Seuwen (2002) cloned full-length ADCY5. EST database analysis revealed 2 alternative polyadenylation sites. The deduced protein contains 1,261 amino acids. Semiquantitative RT-PCR detected high expression of ADCY5 in heart and testis, moderate expression in brain, prostate, ovary, small intestine, and colon, and low expression in lung and liver. </p><p>Mencacci et al. (2015) found expression of the ADCY5 gene in multiple human brain regions, with highest expression in the putamen and adult striatum. ADCY5 expression progressively increased in the striatum during embryonic development. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ludwig and Seuwen (2002) determined that the ADCY5 gene contains 21 exons and spans 167 kb. The first exon is 95 kb upstream of the clustered next 20 exons. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
<span class="mim-text-font">
|
|
<p>By Southern blot analysis of somatic cell hybrid DNAs, Gaudin et al. (1994) mapped the ADCY5 gene to chromosome 3. Using isotopic in situ hybridization, Haber et al. (1994) mapped the ADCY5 gene to 3q13.2-q21. By fluorescence in situ hybridization, Edelhoff et al. (1995) mapped the ADCY5 gene to human chromosome 3q13 and to mouse chromosome 16 in the B5 region. In both species, the gene maps close to GAP43 (162060). </p><p>Stumpf (2021) mapped the ADCY5 gene to chromosome 3q21.1 based on an alignment of the ADCY5 sequence (GenBank AF497517) with the genomic sequence (GRCh38).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Autosomal Dominant Dyskinesia with Orofacial Involvement</em></strong></p><p>
|
|
In affected members of a large German family with autosomal dominant dyskinesia with orofacial involvement (DSKOD; 606703), Chen et al. (2012) identified a heterozygous missense mutation in the ADCY5 gene (A726T; 600293.0001). The family had previously been reported by Bird and Hall (1978). Chen et al. (2015) identified this same heterozygous mutation in a large American family with the disorder; the family had previously been reported by Bird et al. (1976) and Fernandez et al. (2001). In vitro functional expression studies performed by Chen et al. (2014) showed that mutant A726T ADCY5 caused a significant increase in cAMP production in response to beta-adrenergic stimulation compared to wildtype, consistent with a gain of function. </p><p>In 2 unrelated teenaged girls of European ancestry with DSKOD, Chen et al. (2014) identified a de novo heterozygous mutation in the ADCY5 gene (R418W; 600293.0002). The mutations were found by whole-exome sequencing. In vitro functional expression studies showed that both mutant A726T and R418W ADCY5 caused a significant increase in cAMP production in response to beta-adrenergic stimulation compared to wildtype, consistent with a gain of function. One of the girls with a more severe phenotype also carried a de novo heterozygous N1882S variant in the DOCK3 gene (603123), which may have a role in neuronal activity and could have possibly contributed to the phenotype. In addition, sequence reads suggested that the girl with the less severe phenotype may have been somatic mosaic for the R418W mutation. Chen et al. (2014) postulated that these findings may have played a role in the phenotypic variability observed in the 2 patients. </p><p>In a French father and son with DSKOD, Carapito et al. (2015) identified a heterozygous splice site mutation in the ADCY5 gene (600293.0003). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells had decreased ADCY5 mRNA levels, consistent with degradation of the mutant transcript, a loss of function, and haploinsufficiency. The patients had an early onset hyperkinetic movement disorder with dystonia and chorea, but no facial myokymia, thus expanding the phenotype. The findings also suggested that haploinsufficiency of ADCY5 is pathogenic, although a gain-of-function effect could not be excluded. </p><p>In a 14-year-old boy (L-3482) adopted from Southeastern Europe with DSKOD, Westenberger et al. (2017) identified a heterozygous missense mutation in the ADCY5 gene (D1015E; 600293.0004). The mutation, which was found by direct sequencing, was not present in the ExAC database. Functional studies of the variant and studies of patient cells were not performed. In addition to a hyperkinetic movement disorder, the patient had paroxysmal limb weakness reminiscent of alternating hemiplegia of childhood. The report further expanded the phenotype associated with ADCY5 mutations. </p><p>In a 21-year-old woman with DSKOD, Dean et al. (2019) identified a de novo heterozygous missense mutation in the ADCY5 gene (Y233H; 600293.0005) affecting a conserved residue in the M1 domain. The mutation, which was found by whole-genome sequencing, was not present in the ExAC or 1000 Genomes Project databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to be likely pathogenic according to ACMG criteria. In addition to dyskinesia and dystonia, the patient had spastic paraplegia and mild distal sensory impairment. Dean et al. (2019) noted that a heterozygous missense variant (E908K) identified by Waalkens et al. (2018) in a patient with spastic paraparesis and mild dystonia affected the M2 domain. </p><p>In an 18-year-old man (INDF10_3) of Indian origin with DSKOD, Kumar et al. (2019) identified a de novo heterozygous missense mutation in the ADCY5 gene (M1029K; 600293.0006). The mutation was found by whole-genome sequencing and confirmed by Sanger sequencing and filtered against control databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to be pathogenic according to ACMG criteria. The patient had myoclonic dystonia, congenital encephalopathy, and daily paroxysmal ballismus. </p><p><strong><em>Autosomal Recessive Dyskinesia with Orofacial Involvement</em></strong></p><p>
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In 2 sibs with autosomal recessive dyskinesia with orofacial involvement (DSKOR; 619647), Barrett et al. (2017) identified compound heterozygous mutations in the ADCY5 gene (600293.0007 and 600293.0008). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed. The parents, who were heterozygous carriers of 1 of the mutations, were clinically unaffected. </p><p>In 6 sibs, born of consanguineous Arab parents, with DSKOR, Bohlega et al. (2019) identified a homozygous missense mutation in the ADCY5 gene (D588N; 600293.0009). The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. The parents, who were heterozygous carriers of the mutation, were clinically unaffected. </p><p><strong><em>Neurodevelopmental Disorder with Hyperkinetic Movements and Dyskinesia</em></strong></p><p>
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In 2 sibs, born of unrelated Japanese parents, with neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD; 619651), Okamoto et al. (2021) identified a homozygous missense mutation affecting the C terminus of the ADCY5 gene (R1238W; 600293.0010). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. At 3 and 1.5 years of age, the patients had severe intellectual disability, axial hypotonia with inability to control the heard, poor eye contact, and dystonic posturing. The parents, who were heterozygous carriers of the mutation, were clinically unaffected. </p><p>In 3 sibs, born of consanguineous Egyptian parents, with NEDHYD, Kaiyrzhanov et al. (2021) identified a homozygous splice site mutation in the ADCY5 gene (600293.0011). The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro minigene constructs confirmed that the mutation resulted in splicing defects of ADCY5. Functional studies of the variant were not performed, but it was predicted to result in a loss of function. The patients had a severe form of the disorder with poor overall growth, various involuntary movements, severe intellectual disability, and inability to walk or talk. One had cardiomyopathy and died at 4.5 years of age. The carrier parents were clinically unaffected. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between variation in the ADCY5 gene and fasting plasma glucose, birth weight, and 2-hour plasma glucose levels as quantitative traits, see 613460.</p>
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</span>
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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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<span class="mim-text-font">
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<p>Kim et al. (2006) found that Adcy5-null mice had decreased behavioral responses to morphine, including locomotor activation, analgesia, tolerance, reward, physical dependence, and withdrawal symptoms, compared to wildtype mice. Adcy5-null mice also showed attenuated responses to selective mu (600018) and delta (165195) opioid receptor agonists, whereas responses to kappa (165196) opioid receptor agonists were similar to wildtype mice. The results indicated that ADCY5 is an important component of mu- and delta-opioid receptor signal transduction mechanisms in the striatum and provided further support for the importance of the cAMP pathway as a mediator of opioid action. </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>11 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 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT</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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ADCY5, ALA726THR
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<br />
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SNP: rs796065306,
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ClinVar: RCV000030679, RCV000484892
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</span>
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</div>
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<span class="mim-text-font">
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<p>In affected members of a large multigenerational German family with autosomal dominant dyskinesia with orofacial involvement (DSKOD; 606703), previously reported by Bird and Hall (1978) and Fernandez et al. (2001), Chen et al. (2012) identified a heterozygous c.2176G-A transition in exon 10 of the ADCY5 gene, resulting in an ala726-to-thr (A726T) substitution at a highly conserved residue between the first intracellular cyclase homology domain and the second membrane-spanning domain. The mutation was identified by exome sequencing of 1 affected individual and was not found in 3,510 control exomes. Chen et al. (2012) noted that Adcy5-null mice develop a movement disorder that is worsened by stress (Kim et al., 2006), supporting the pathogenicity of the A726T mutation. </p><p>In vitro functional expression studies performed by Chen et al. (2014) showed that mutant A726T ADCY5 caused a significant increase in cAMP production in response to beta-adrenergic stimulation compared to wildtype, consistent with a gain of function. </p><p>In affected members of a large 5-generation family (EHC) with DSKOD, previously reported by Bird et al. (1976) and Fernandez et al. (2001), Chen et al. (2015) identified a heterozygous A726T mutation in the ADCY5 gene. The mutation, which was found by direct Sanger sequencing, segregated completely with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. Haplotype analysis showed that the German family reported by Chen et al. (2012) and family EHC, from the US, did not share a common haplotype; the mutations arose independently. The EHC family had originally been diagnosed with benign hereditary chorea (see 118700). Chen et al. (2015) noted that the A726T mutation is associated with a relatively mild phenotype. Fernandez et al. (2001) stated that the phenotype in this family was nonprogressive in adulthood and that dementia was not observed, although some patients had educational or behavioral difficulties, possibly resulting from social isolation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT</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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ADCY5, ARG418TRP
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<br />
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SNP: rs864309483,
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ClinVar: RCV000202545, RCV000255111, RCV000622463
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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 teenaged girls of European ancestry with autosomal dominant dyskinesia with orofacial involvement (DSKOD; 606703), Chen et al. (2014) identified a de novo heterozygous c.1252C-T transition in the ADCY5 gene, resulting in an arg418-to-trp (R418W) substitution at a conserved residue in the sixth helical segment of the first transmembrane domain. The mutations were found by whole-exome sequencing. In vitro functional expression studies showed that mutant R418W ADCY5 caused a significant increase in cAMP production in response to beta-adrenergic stimulation compared to wildtype, consistent with a gain of function. </p><p>In 2 unrelated patients of UK and Pakistani ancestry with DSKOD, Mencacci et al. (2015) identified a heterozygous R418W mutation. The mutation was found by exome sequencing and confirmed by Sanger sequencing. In the first family, the mutation was inherited from the patient's mildly affected father who was somatic mosaic for the mutation. R418W occurred de novo in the proband from family 2. Functional studies of the variant were not performed. The probands had typical features of the disorder with onset of progressive and severe choreodystonic dyskinesias with orofacial involvement in the first years of life. The hyperkinetic movements were exacerbated by action, excitement, stress, and fatigue. </p><p>Shetty et al. (2020) reported an Indian man with DKSOD who had the R418W mutation (c.1252C-T, NM_183357.2) in mosaic state with low mutant read depth. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was absent in the parents. The patient had paroxysmal involuntary movements during sleep. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT</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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ADCY5, IVS8DS, G-A, +1
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<br />
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SNP: rs797045002,
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ClinVar: RCV000202586, RCV002298522
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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 French father and son with autosomal dominant dyskinesia with facial involvement (DSKOD; 606703), Carapito et al. (2015) identified a heterozygous G-to-A transition (c.2088+1G-A) in intron 8 of the ADCY5 gene, resulting in a splicing defect. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient cells had decreased ADCY5 mRNA levels, consistent with degradation of the mutant transcript, a loss of function, and haploinsufficiency. The patients had an early-onset hyperkinetic movement disorder with dystonia and chorea, but no facial myokymia, thus expanding the phenotype. The findings also suggested that haploinsufficiency of ADCY5 is pathogenic, although the authors could not rule out a gain-of-function effect via production of a long alternatively spliced mRNA. </p><p>Meneret et al. (2019) reported an 11-year-old boy with DSKOD who was mosaic for the c.2088+1G-A mutation. These authors postulated a gain-of-function effect, although no functional studies of the variant or studies of patient cells were performed. The patient had a remarkable favorable response to caffeinated coffee, which resulted in near complete resolution of the dyskinetic episodes. Meneret et al. (2019) postulated that the caffeine antagonized adenosine A2A receptors, which would inhibit the ADCY5 enzyme. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0004 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT</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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ADCY5, ASP1015GLU
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<br />
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SNP: rs1007363034,
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ClinVar: RCV001789712
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 14-year-old boy (L-3482) adopted from Southeastern Europe with autosomal dominant dyskinesia with orofacial involvement (DSKOD; 606703), Westenberger et al. (2017) identified a heterozygous c.3045C-A transition in the ADCY5 gene, resulting in an asp1015-to-glu (D1015E) substitution at a conserved residue in the second cytoplasmic domain that forms the catalytic pocket. The mutation, which was found by direct sequencing, was not present in the ExAC database. Functional studies of the variant and studies of patient cells were not performed. In addition to a hyperkinetic movement disorder, the patient had paroxysmal limb weakness reminiscent of alternating hemiplegia of childhood. The report further expanded the phenotype associated with ADCY5 mutations. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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|
<span class="mim-font">
|
|
<strong>.0005 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT</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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ADCY5, TYR233HIS
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<br />
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SNP: rs2107658582,
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ClinVar: RCV001789713
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 21-year-old woman with hyperkinetic movement disorder with autosomal dominant dyskinesia with orofacial involvement (DSKOD; 606703), Dean et al. (2019) identified a de novo heterozygous c.697T-C transition in exon 1 of in the ADCY5 gene, resulting in a tyr233-to-his (Y233H) substitution at a conserved residue in the M1 domain. The mutation, which was found by whole-genome sequencing, was not present in the ExAC or 1000 Genomes Project databases. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to be likely pathogenic according to ACMG criteria. In addition to dyskinesia and dystonia, the patient had spastic paraplegia and mild distal sensory impairment, further expanding the phenotype. </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>.0006 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL DOMINANT</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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ADCY5, MET1029LYS
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<br />
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SNP: rs864309484,
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ClinVar: RCV000202493
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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 an 18-year-old man (INDF10_3) of Indian origin with autosomal dominant dyskinesia with orofacial involvement (DSKOD; 606703), Kumar et al. (2019) identified a de novo heterozygous c.3086T-A transversion (c.3086T-A, NM_183357.2) in exon 18 of the ADCY5 gene, resulting in a met1029-to-lys (M1029K) substitution. The mutation was found by whole-genome sequencing and confirmed by Sanger sequencing and filtered against control databases. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to be pathogenic according to ACMG criteria. The patient had myoclonic dystonia, congenital encephalopathy, and daily paroxysmal ballismus. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0007 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL RECESSIVE</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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ADCY5, ARG1013CYS
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<br />
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SNP: rs1365372289,
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gnomAD: rs1365372289,
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ClinVar: RCV000623061, RCV001789708
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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 sibs with autosomal recessive dyskinesia with orofacial involvement (DSKOR; 619647), Barrett et al. (2017) identified compound heterozygous mutations in the ADCY5 gene: a c.3037C-T transition (c.3037C-T, NM_183357), resulting in an arg1013-to-cys (R1013C) substitution at a conserved residue, and a 20-bp deletion (c.409_428del20; 600293.0008), predicted to result in a frameshift and premature termination (Gly137CysfsTer184). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. R1013C was not present in the ExAC database. Functional studies of the variants and studies of patient cells were not performed. The parents, who were each a heterozygous carrier of 1 of the mutations, were clinically unaffected. </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>.0008 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL RECESSIVE</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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ADCY5, 20-BP DEL, NT409
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<br />
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SNP: rs1553751262,
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ClinVar: RCV000624020, RCV001789709
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the 20-bp deletion (c.409_428del20, NM_183357) in the ADCY5 gene, predicted to result in a frameshift and premature termination (Gly137CysfsTer184), that was found in compound heterozygous state in 2 sibs with autosomal recessive dyskinesia with orofacial involvement (DSKOR; 619647) by Barrett et al. (2017), see 600293.0007. </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>.0009 DYSKINESIA WITH OROFACIAL INVOLVEMENT, AUTOSOMAL RECESSIVE</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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ADCY5, ASP588ASN
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<br />
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SNP: rs2108390731,
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ClinVar: RCV001789714, RCV004699475
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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 6 sibs, born of consanguineous Arab parents, with 2 sibs with autosomal recessive dyskinesia with orofacial involvement (DSKOR; 619647), Bohlega et al. (2019) identified a homozygous c.1762G-A transition in exon 6 of the ADCY5 gene, resulting in an asp588-to-asn (D588N) substitution at a highly conserved residue. The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. The parents, who were heterozygous carriers of the mutation, were clinically unaffected. </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>.0010 NEURODEVELOPMENTAL DISORDER WITH HYPERKINETIC MOVEMENTS AND DYSKINESIA</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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ADCY5, ARG1238TRP
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<br />
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SNP: rs2108148749,
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ClinVar: RCV001789715
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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 sibs, born of unrelated Japanese parents, with neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD; 619651), Okamoto et al. (2021) identified a homozygous c.3712C-T transition (c.3712C-T, NM_183357.2) in exon 21 of the ADCY5 gene, resulting in an arg1238-to-trp (R1238W) substitution at a highly conserved residue in the C terminus. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. The variant was not present in public databases. Functional studies of the variant and studies of patient cells were not performed. At 3 and 1.5 years of age, the patients had severe intellectual disability, axial hypotonia with inability to control the heard, poor eye contact, and dystonic posturing. The parents, who were heterozygous carriers of the mutation, were clinically unaffected. </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>.0011 NEURODEVELOPMENTAL DISORDER WITH HYPERKINETIC MOVEMENTS AND DYSKINESIA</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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ADCY5, IVS7DS, G-T, +1
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<br />
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SNP: rs2108384208,
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ClinVar: RCV001789716
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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 3 sibs, born of consanguineous Egyptian parents, with neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD; 619651), Kaiyrzhanov et al. (2021) identified a homozygous G-to-T transversion (c.897+1G-T, NM_001199642.1) in intron 7 of the ADCY5 gene, predicted to result in a splicing defect. The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro minigene constructs confirmed that the mutation resulted in splicing defects of ADCY5. Functional studies of the variant were not performed, but it was predicted to result in a loss of function. The patients had a severe form of the disorder with poor overall growth, various involuntary movements, severe intellectual disability, and inability to walk or talk. One had cardiomyopathy and died at 4.5 years of age. The carrier parents were clinically unaffected. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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Barrett, M. J., Williams, E. S., Chambers, C., Dhamija, R.
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Neurol. Genet. 3: 193, 2017.
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[PubMed: 28971144]
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[Full Text: https://doi.org/10.1212/NXG.0000000000000193]
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Bird, T. D., Carlson, C. B., Hall, J. G.
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<strong>Familial essential ('benign') chorea.</strong>
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J. Med. Genet. 13: 357-362, 1976.
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<p class="mim-text-font">
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Bird, T. D., Hall, J. G.
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Clin. Genet. 14: 271-272, 1978.
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<p class="mim-text-font">
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Bohlega, S. A., Abou-Al-Shaar, H., AlDakheel, A., Alajlan, H., Bohlega, B. S., Meyer, B. F., Monies, D., Cupler, E. J.,, Al-Saif, A. M.
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<p class="mim-text-font">
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Carapito, R., Paul, N., Untrau, M., Le Gentil, M., Ott, L., Alsaleh, G., Jochem, P., Radosavljevic, M., Le Caignec, C., David, A., Damier, P., Isidor, B., Bahram, S.
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<strong>A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia.</strong>
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Chen, D.-H., Meneret, A., Friedman, J. R., Korvatska, O., Gad, A., Bonkowski, E. S., Stessman, H. A., Doummar, D., Mignot, C., Anheim, M., Bernes, S., Davis, M. Y., and 19 others.
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<strong>ADCY5-related dyskinesia: broader spectrum and genotype-phenotype correlations.</strong>
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[Full Text: https://doi.org/10.1212/WNL.0000000000002058]
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Chen, Y.-Z., Friedman, J. R., Chen, D.-H., Chan, G. C.-K., Bloss, C. S., Hisama, F. M., Topol, S. E., Carson, A. R., Pham, P. H., Bonkowski, E. S., Scott, E. R., Lee, J. K., and 13 others.
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<strong>Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia.</strong>
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Ann. Neurol. 75: 542-549, 2014.
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[PubMed: 24700542]
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[Full Text: https://doi.org/10.1002/ana.24119]
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Chen, Y.-Z., Matsushita, M. M., Robertson, P., Rieder, M., Girirajan, S., Antonacci, F., Lipe, H., Eichler, E. E., Nickerson, D. A., Bird, T. D., Raskind, W. H.
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<strong>Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5.</strong>
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Arch. Neurol. 69: 630-635, 2012.
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[PubMed: 22782511]
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[Full Text: https://doi.org/10.1001/archneurol.2012.54]
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Dean, M., Messiaen, L., Cooper, G. M., Amaral, M. D., Rashid, S., Korf, B. R., Standaert, D. G.
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<strong>Child neurology: spastic paraparesis and dystonia with a novel ADCY5 mutation.</strong>
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Neurology 93: 510-514, 2019.
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[PubMed: 31501304]
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[Full Text: https://doi.org/10.1212/WNL.0000000000008089]
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Edelhoff, S., Villacres, E. C., Storm, D. R., Disteche, C. M.
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<strong>Mapping of adenylyl cyclase genes type I, II, III, IV, V, and VI in mouse.</strong>
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Mammalian Genome 6: 111-113, 1995.
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[PubMed: 7766992]
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Fernandez, M., Raskind, W., Matsushita, M., Wolff, J., Lipe, H., Bird, T.
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Neurology 57: 106-110, 2001.
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<p class="mim-text-font">
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Fernandez, M., Raskind, W., Wolff, J., Matsushita, M., Yuen, E., Graf, W., Lipe, H., Bird, T.
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Ann. Neurol. 49: 486-492, 2001.
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[PubMed: 11310626]
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<p class="mim-text-font">
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Gaudin, C., Homcy, C. J., Ishikawa, Y.
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<strong>Mammalian adenylyl cyclase family members are randomly located on different chromosomes.</strong>
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Hum. Genet. 94: 527-529, 1994.
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[PubMed: 7959689]
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Haber, N., Stengel, D., Defer, N., Roeckel, N., Mattei, M.-G., Hanoune, J.
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<strong>Chromosomal mapping of human adenylyl cyclase genes type III, type V and type VI.</strong>
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Hum. Genet. 94: 69-73, 1994.
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<li>
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<p class="mim-text-font">
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Kaiyrzhanov, R., Zaki, M. S., Maroofian, R., Dominik, N., Rad, A., Vona, B., Houlden, H.
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<strong>A novel homozygous ADCY5 variant is associated with a neurodevelopmental disorder and movement abnormalities.</strong>
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Mov. Disord. Clin. Pract. 8: 1140-1143, 2021.
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<p class="mim-text-font">
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Kim, K.-S., Lee, K.-W., Lee, K.-W., Im, J.-Y., Yoo, J. Y., Kim, S.-W., Lee, J.-K., Nestler, E. J., Han, P.-L.
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<strong>Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action.</strong>
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Proc. Nat. Acad. Sci. 103: 3908-3913, 2006.
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<li>
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<p class="mim-text-font">
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|
Kumar, K. R., Davis, R. L., Tchan, M. C., Wali, G. M., Mahant, N., Ng, K., Kotschet, K., Siow, S.-F., Gu, J., Walls, Z., Kang, C., Wali, G., and 16 others.
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<strong>Whole genome sequencing for the genetic diagnosis of heterogenous dystonia phenotypes.</strong>
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Parkinsonism Relat. Disord. 69: 111-118, 2019.
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</p>
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<li>
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<p class="mim-text-font">
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Ludwig, M.-G., Seuwen, K.
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<strong>Characterization of the human adenylyl cyclase gene family: cDNA, gene structure, and tissue distribution of the nine isoforms.</strong>
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J. Recept. Signal Transduct. Res. 22: 79-110, 2002.
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[PubMed: 12503609]
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[Full Text: https://doi.org/10.1081/rrs-120014589]
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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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Mencacci, N. E., Erro, R., Wiethoff, S., Hersheson, J., Ryten, M., Balint, B., Ganos, C., Stamelou, M., Quinn, N., Houlden, H., Wood, N. W., Bhatia, K. P.
|
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<strong>ADCY5 mutations are another cause of benign hereditary chorea.</strong>
|
|
Neurology 85: 80-88, 2015.
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|
|
|
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[PubMed: 26085604]
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[Full Text: https://doi.org/10.1212/WNL.0000000000001720]
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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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Meneret, A., Gras, D., McGovern, E., Roze, E.
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<strong>Caffeine and the dyskinesia related to mutations in the ADCY5 gene.</strong>
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Ann. Intern. Med. 171: 439, 2019.
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[PubMed: 31181574]
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[Full Text: https://doi.org/10.7326/L19-0038]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Okamoto, N., Miya, F., Kitai, Y., Tsunoda, T., Kato, M., Saitoh, S., Kanemura, Y., Kosaki, K.
|
|
<strong>Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability.</strong>
|
|
Neurol. Sci. 42: 2975-2978, 2021.
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[PubMed: 33704598]
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[Full Text: https://doi.org/10.1007/s10072-021-05152-y]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Shetty, K., Sarma, A. S., Devan, M., Dalal, A., Dash, G. K., Jannabhatla, A., Patil, S. J.
|
|
<strong>Recurrent ADCY5 mutation in mosaic form with nocturnal paroxysmal dyskinesias and video electroencephalography documentation of dramatic response to caffeine treatment. (Letter)</strong>
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J. Mov. Disord. 13: 238-240, 2020.
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[PubMed: 32713175]
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[Full Text: https://doi.org/10.14802/jmd.20014]
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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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Stumpf, A. M.
|
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<strong>Personal Communication.</strong>
|
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Baltimore, Md. 12/08/2021.
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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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Waalkens, A. J. E., Vansenne, F., van der Hout, A. H., Zutt, R., Mourmans, J., Tolosa, E., de Koning, T. J., Tijssen, M. A. J.
|
|
<strong>Expanding the ADCY5 phenotype toward spastic paraparesis: a mutation in the M2 domain.</strong>
|
|
Neurol. Genet. 4: e214, 2018.
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|
|
[PubMed: 29473048]
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[Full Text: https://doi.org/10.1212/NXG.0000000000000214]
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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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Westenberger, A., Max, C., Bruggemann, N., Domingo, A., Grutz, K., Pawlack, H., Weissbach, A., Kuhn, A. A., Spiegler, J., Lang, A. E., Sperner, J., Fung, V. S. C., Schallner, J., Gillessen-Kaesbach, G., Munchau, A., Klein, C.
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<strong>Alternating hemiplegia of childhood as a new presentation of adenylate cyclase 5-mutation-associated disease: a report of two cases.</strong>
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J. Pediat. 181: 306-308, 2017.
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[PubMed: 27931826]
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[Full Text: https://doi.org/10.1016/j.jpeds.2016.10.079]
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Hilary J. Vernon - updated : 06/02/2022<br>Cassandra L. Kniffin - updated : 01/12/2022<br>Anne M. Stumpf - updated : 12/08/2021<br>Cassandra L. Kniffin - updated : 12/07/2021<br>Cassandra L. Kniffin - updated : 4/10/2014<br>Cassandra L. Kniffin - updated : 8/20/2012<br>Cassandra L. Kniffin - updated : 7/16/2007<br>Patricia A. Hartz - updated : 10/11/2006
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Victor A. McKusick : 1/9/1995
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