5082 lines
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Entry
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- *146920 - ADENOSINE DEAMINASE, RNA-SPECIFIC; ADAR
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- OMIM
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<p>
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<span class="h4">*146920</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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="#geneFunction">Gene Function</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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<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/146920">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<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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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000160710;t=ENST00000368474" 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=103" 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=146920" 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=ENSG00000160710;t=ENST00000368474" 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_001025107,NM_001111,NM_001193495,NM_001365045,NM_001365046,NM_001365047,NM_001365048,NM_001365049,NM_015840,NM_015841,XM_011509061,XM_011509062,XM_047428340,XM_047428386,XM_047428405,XM_047428441" 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_001111" 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=146920" 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=07528&isoform_id=07528_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/ADAR" 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/577170,915284,2326524,2326526,2795789,2795790,2795791,12711291,12711292,12711307,12711310,23398522,31874703,34364836,62089368,70167113,119573568,119573569,119573570,119573571,119573572,119573573,119573574,119573575,123204181,123204184,221044884,301601658,313104303,632933512,767908090,1034554638,1388742732,1433353887,1433354001,1433354013,1433354019,1433354021,1433354030,1433354056,2217263118,2217263120,2217263122,2217263124,2462502092,2462502094,2462502097,2462502099,2462502101,2462502103" 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/P55265" 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=103" 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=ENSG00000160710;t=ENST00000368474" 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=ADAR" 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=ADAR" 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+103" 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/ADAR" 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:103" 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/103" 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=chr1&hgg_gene=ENST00000368474.9&hgg_start=154582057&hgg_end=154627997&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:225" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/adar" 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=146920[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=146920[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/ADAR/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/ENSG00000160710" 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=ADAR" 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=ADAR" 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=ADAR" 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=ADAR&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/PA24555" 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:225" 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://www.mousephenotype.org/data/genes/MGI:1889575" 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/ADAR#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:1889575" 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/103/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=103" 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=WBGene00000080;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-000616-5" 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">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<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:103" 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=ADAR&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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|
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<a id="title" class="mim-anchor"></a>
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<div>
|
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 239085000<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
146920
|
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</span>
|
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</span>
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</div>
|
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</div>
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<div>
|
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
|
<span class="mim-font">
|
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ADENOSINE DEAMINASE, RNA-SPECIFIC; ADAR
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
|
<br />
|
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</div>
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<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ADENOSINE DEAMINASE, RNA-SPECIFIC, 1; ADAR1<br />
|
|
DOUBLE-STRANDED RNA-SPECIFIC ADENOSINE DEAMINASE; DSRAD; DRADA<br />
|
|
INTERFERON-INDUCED PROTEIN 4; IFI4<br />
|
|
G1P1
|
|
</span>
|
|
</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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ADAR" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ADAR</a></em></strong>
|
|
</span>
|
|
</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/1/1194?start=-3&limit=10&highlight=1194">1q21.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:154582057-154627997&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'})">1:154,582,057-154,627,997</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=615010,127400" 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="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/1194?start=-3&limit=10&highlight=1194">
|
|
1q21.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Aicardi-Goutieres syndrome 6
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/615010"> 615010 </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>
|
|
|
|
|
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|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
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|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Dyschromatosis symmetrica hereditaria
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/127400"> 127400 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/146920" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/146920" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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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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<strong>TEXT</strong>
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<p>Double-stranded RNA-specific adenosine deaminase (DSRAD), or RNA-specific adenosine deaminase (ADAR), was identified as a developmentally regulated dsRNA unwinding activity in early antisense experiments with Xenopus oocytes (<a href="#2" class="mim-tip-reference" title="Bass, B. L., Weintraub, H. <strong>An unwinding activity that covalently modifies its double-stranded RNA substrate.</strong> Cell 55: 1089-1098, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3203381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3203381</a>] [<a href="https://doi.org/10.1016/0092-8674(88)90253-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3203381">Bass and Weintraub, 1988</a>). The enzyme converts adenosine to inosine in dsRNA, which destabilizes the dsRNA helix. The RNA modifying activity of DSRAD is important for various functions. Among these are site-specific RNA editing of transcripts of the glutamate receptors (see <a href="/entry/138248">138248</a>), which are channels for the neurotransmitter L-glutamate in the brain. DSRAD also functions to modify viral RNA genomes and may be responsible for hypermutation of certain negative-stranded viruses, such as measles, which may result in lethal measles inclusion body encephalitis (<a href="#23" class="mim-tip-reference" title="Weier, H.-U. G., George, C. X., Greulich, K. M., Samuel, C. E. <strong>The interferon-inducible, double-stranded RNA-specific adenosine deaminase gene (DSRAD) maps to human chromosome 1q21.1-21.2.</strong> Genomics 30: 372-375, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8586444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8586444</a>] [<a href="https://doi.org/10.1006/geno.1995.0034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8586444">Weier et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8586444+3203381" 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>Cloning and Expression</strong>
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<p><a href="#9" class="mim-tip-reference" title="Kim, U., Wang, Y., Sanford, T., Zeng, Y., Nishikura, K. <strong>Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing.</strong> Proc. Nat. Acad. Sci. 91: 11457-11461, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7972084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7972084</a>] [<a href="https://doi.org/10.1073/pnas.91.24.11457" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7972084">Kim et al. (1994)</a> cloned a human gene for double-stranded RNA adenosine deaminase using degenerate PCR with primers based on partial bovine amino acid sequence. A cDNA was obtained from a human natural killer cell library. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7972084" 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>From an interferon-alpha (IFNA1; <a href="/entry/147660">147660</a>)-treated human amnion U cell line, <a href="#15" class="mim-tip-reference" title="Patterson, J. B., Samuel, C. E. <strong>Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase.</strong> Molec. Cell. Biol. 15: 5376-5388, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7565688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7565688</a>] [<a href="https://doi.org/10.1128/MCB.15.10.5376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7565688">Patterson and Samuel (1995)</a> cloned ADAR, which they designated K88. The 5-prime end of the transcript, including part of the coding region, is GC-rich and the 3-prime untranslated region (UTR) contains 3 motifs associated with RNA instability. The deduced 1,226-amino acid protein has a calculated molecular mass of 136 kD. It has 2 N-terminal repeats of a 26-amino acid sequence that displayed 31% identity (58% similarity) with the N-terminal region of vaccinia virus E3L protein. Between these 2 repeats were 2 unique tandem repeats that shared 79% identity (86% similarity) with each other over 49 amino acids. This region is followed by 3 copies of the double-stranded RNA (dsRNA)-binding subdomain R motif, and a conserved C-terminal domain of 380 amino acids. Northern blot analysis detected a 6.7-kb transcript in all tissues examined, including heart, brain, lung, liver, skeletal muscle, kidney, and pancreas, and in human amnion U cells. Western blot analysis detected proteins of 150 and 110 kD in human neuroblastoma and amnion U cell lines. Using domain-specific antibodies, <a href="#15" class="mim-tip-reference" title="Patterson, J. B., Samuel, C. E. <strong>Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase.</strong> Molec. Cell. Biol. 15: 5376-5388, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7565688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7565688</a>] [<a href="https://doi.org/10.1128/MCB.15.10.5376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7565688">Patterson and Samuel (1995)</a> determined that the 110-kD protein lacks the N-terminal domain found in the full-length 150-kD protein. Immunohistochemical analysis and cell fractionation detected the 150-kD protein in both the nucleus and cytoplasm, and the 110-kD protein in the nucleus only. <a href="#1" class="mim-tip-reference" title="Agranat, L., Raitskin, O., Sperling, J., Sperling, R. <strong>The editing enzyme ADAR1 and the mRNA surveillance protein hUpf1 interact in the cell nucleus.</strong> Proc. Nat. Acad. Sci. 105: 5028-5033, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18362360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18362360</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18362360[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.0710576105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18362360">Agranat et al. (2008)</a> stated that the 2 major ADAR1 isoforms are expressed from 2 distinct promoters. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18362360+7565688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By Western blot analysis of human amnion U cells, <a href="#15" class="mim-tip-reference" title="Patterson, J. B., Samuel, C. E. <strong>Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase.</strong> Molec. Cell. Biol. 15: 5376-5388, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7565688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7565688</a>] [<a href="https://doi.org/10.1128/MCB.15.10.5376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7565688">Patterson and Samuel (1995)</a> showed that expression of the 110-kD ADAR protein was constitutive, whereas the expression of full-length 150-kD ADAR protein was induced by interferon-alpha (<a href="/entry/147660">147660</a>). Western blot analysis of interferon-treated U cell nuclear lysates subjected to Northwestern (RNA-protein) blot analysis or RNA-Sepharose affinity chromatography demonstrated that both ADAR isoforms bound to dsRNA, but neither bound to single-stranded RNA (ssRNA). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7565688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="O'Connell, M. A., Krause, S., Higuchi, M., Hsuan, J. J., Totty, N. F., Jenny, A., Keller, W. <strong>Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase.</strong> Molec. Cell. Biol. 15: 1389-1397, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7862132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7862132</a>] [<a href="https://doi.org/10.1128/MCB.15.3.1389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7862132">O'Connell et al. (1995)</a> cloned the rat DSRAD gene and showed that the predicted protein is 79% identical to the human sequence. <a href="#14" class="mim-tip-reference" title="O'Connell, M. A., Krause, S., Higuchi, M., Hsuan, J. J., Totty, N. F., Jenny, A., Keller, W. <strong>Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase.</strong> Molec. Cell. Biol. 15: 1389-1397, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7862132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7862132</a>] [<a href="https://doi.org/10.1128/MCB.15.3.1389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7862132">O'Connell et al. (1995)</a> also found that the protein is ubiquitously expressed and showed by immunohistochemistry that it has a widespread distribution in the rat brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7862132" 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="#7" class="mim-tip-reference" title="Herbert, A., Wagner, S., Nickerson, J. A. <strong>Induction of protein translation by ADAR1 within living cell nuclei is not dependent on RNA editing.</strong> Molec. Cell 10: 1235-1246, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12453429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12453429</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00737-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12453429">Herbert et al. (2002)</a> reported that ADAR, which catalyzes the deamination of adenosine to inosine in dsRNA substrates, induces translation within the nucleus, possibly at the surface of the nucleolus. They found that this activity does not depend on RNA editing. The authors defined 2 regions within ADAR that act independently of each other to induce translation: the first includes the dsRNA-binding domains (DRBMs) of ADAR, while the second maps to the C-terminal portion of the catalytic domain. Point mutations within each domain were identified that reduced nuclear translation; those in the DRBM region also diminished RNA binding. This report added to the growing functionality ascribed to the nucleus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12453429" 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 crosslinking and coimmunoprecipitation experiments on HeLa cell nuclear extracts, <a href="#1" class="mim-tip-reference" title="Agranat, L., Raitskin, O., Sperling, J., Sperling, R. <strong>The editing enzyme ADAR1 and the mRNA surveillance protein hUpf1 interact in the cell nucleus.</strong> Proc. Nat. Acad. Sci. 105: 5028-5033, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18362360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18362360</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18362360[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.0710576105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18362360">Agranat et al. (2008)</a> showed that ADAR1 associated with the RNA surveillance protein HUPF1 (RENT1; <a href="/entry/601430">601430</a>) in the supraspliceosome, a 21-megadalton nuclear ribonucleoprotein complex. The interaction did not depend on RNA. Knockdown of ADAR1 with small interfering RNA upregulated the expression of 4 of 6 genes that undergo both A-to-I editing by ADARs and degradation via HUPF1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18362360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To determine the specifics of RNA editing by ADAR1, <a href="#11" class="mim-tip-reference" title="Liddicoat, B. J., Piskol, R., Chalk, A. M., Ramaswami, G., Higuchi, M., Hartner, J. C., Li, J. B., Seeburg, P. H., Walkley, C. R. <strong>RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself.</strong> Science 349: 1115-1120, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26275108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26275108</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26275108[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/10.1126/science.aac7049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26275108">Liddicoat et al. (2015)</a> generated mice with an editing-deficient knockin mutation, Adar1(E861A). Adar1(E861A/E861A) embryos died at approximately embryonic day 13.5, with activated interferon (see <a href="/entry/147660">147660</a>) and double-stranded RNA (dsRNA)-sensing pathways. Genomewide analysis of the in vivo substrates of ADAR1 identified clustered hyperediting within long dsRNA stem loops within 3-prime untranslated regions of endogenous transcripts. Concurrent deletion of the cytosolic sensor of dsRNA MDA5 (<a href="/entry/606951">606951</a>) rescued embryonic death and other phenotypes of Adar1(E861A/E861A). <a href="#11" class="mim-tip-reference" title="Liddicoat, B. J., Piskol, R., Chalk, A. M., Ramaswami, G., Higuchi, M., Hartner, J. C., Li, J. B., Seeburg, P. H., Walkley, C. R. <strong>RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself.</strong> Science 349: 1115-1120, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26275108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26275108</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26275108[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/10.1126/science.aac7049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26275108">Liddicoat et al. (2015)</a> concluded that adenosine-to-inosine editing of endogenous dsRNA is the essential function of ADAR1, preventing the activation of the cytosolic dsRNA response by endogenous transcripts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26275108" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Tan, M. H., Li, Q., Shanmugam, R., Piskol, R., Kohler, J., Young, A. N., Liu, K. I., Zhang, R., Ramaswami, G., Ariyoshi, K., Gupte, A., Keegan, L. P., and 18 others. <strong>Dynamic landscape and regulation of RNA editing in mammals.</strong> Nature 550: 249-254, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29022589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29022589</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29022589[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/10.1038/nature24041" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29022589">Tan et al. (2017)</a> reported dynamic spatiotemporal patterns and novel regulators of RNA editing, discovered through an extensive profiling of adenosine-to-inosine RNA editing in 8,551 human samples (representing 53 body sites from 552 individuals) from the Genotype-Tissue Expression (GTEx) project and in hundreds of other primate and mouse samples. <a href="#18" class="mim-tip-reference" title="Tan, M. H., Li, Q., Shanmugam, R., Piskol, R., Kohler, J., Young, A. N., Liu, K. I., Zhang, R., Ramaswami, G., Ariyoshi, K., Gupte, A., Keegan, L. P., and 18 others. <strong>Dynamic landscape and regulation of RNA editing in mammals.</strong> Nature 550: 249-254, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29022589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29022589</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29022589[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/10.1038/nature24041" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29022589">Tan et al. (2017)</a> showed that editing levels in nonrepetitive coding regions vary more between tissues than editing levels in repetitive regions. Globally, ADAR1 is the primary editor of repetitive sites and ADAR2 (<a href="/entry/601218">601218</a>) is the primary editor of nonrepetitive coding sites, whereas the catalytically inactive ADAR3 (<a href="/entry/602065">602065</a>) predominantly acts as an inhibitor of editing. Cross-species analysis of RNA editing in several tissues revealed that species, rather than tissue type, is the primary determinant of editing levels, suggesting stronger cis-directed regulation of RNA editing for most sites, although the small set of conserved coding sites is under stronger trans-regulation. <a href="#18" class="mim-tip-reference" title="Tan, M. H., Li, Q., Shanmugam, R., Piskol, R., Kohler, J., Young, A. N., Liu, K. I., Zhang, R., Ramaswami, G., Ariyoshi, K., Gupte, A., Keegan, L. P., and 18 others. <strong>Dynamic landscape and regulation of RNA editing in mammals.</strong> Nature 550: 249-254, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29022589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29022589</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29022589[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/10.1038/nature24041" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29022589">Tan et al. (2017)</a> curated an extensive set of ADAR1 and ADAR2 targets and showed that many editing sites display distinct tissue-specific regulation by the ADAR enzymes in vivo. The authors also found that AIMP2 (<a href="/entry/600859">600859</a>), a component of the aminoacyl-tRNA synthetase complex, interacts with both ADAR1 and ADAR2 and reduces editing by enhancing their degradation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29022589" 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="#8" class="mim-tip-reference" title="Ishizuka, J. J., Manguso, R. T., Cheruiyot, C. K., Bi, K., Panda, A., Iracheta-Vellve, A., Miller, B. C., Du, P. P., Yates, K. B., Dubrot, J., Buchumenski, I., Comstock, D. E., and 15 others. <strong>Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade.</strong> Nature 565: 43-48, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30559380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30559380</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30559380[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/10.1038/s41586-018-0768-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30559380">Ishizuka et al. (2019)</a> demonstrated that loss of function of the RNA-editing enzyme ADAR1 in tumor cells profoundly sensitizes tumors to immunotherapy and overcomes resistance to checkpoint blockade. In the absence of ADAR1, A-to-I editing of interferon-inducible RNA species is reduced, leading to double-stranded RNA ligand sensing by PKR (<a href="/entry/176871">176871</a>) and MDA5; this results in growth inhibition and tumor inflammation, respectively. Loss of ADAR1 overcomes resistance to PD1 (<a href="/entry/600244">600244</a>) checkpoint blockade caused by inactivation of antigen presentation by tumor cells. Thus, effective antitumor immunity is constrained by inhibitory checkpoints such as ADAR1 that limit the sensing of innate ligands. The induction of sufficient inflammation in tumors that are sensitized to interferon can bypass the therapeutic requirement for CD8+ T cell recognition of cancer cells and may provide a general strategy to overcome immunotherapy resistance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30559380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By knockout analysis, <a href="#26" class="mim-tip-reference" title="Zhang, T., Yin, C., Fedorov, A., Qiao, L., Bao, H., Beknazarov, N., Wang, S., Gautam, A., Williams, R. M., Crawford, J. C., Peri, S., Studitsky, V., Beg, A. A., Thomas, P. G., Walkley, C., Xu, Y., Poptsova, M., Herbert, A., Balachandran, S. <strong>ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis.</strong> Nature 606: 594-602, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35614224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35614224</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35614224[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/10.1038/s41586-022-04753-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35614224">Zhang et al. (2022)</a> showed that Adar1 repressed production of Z-form double-stranded RNA elements (Z-RNAs), as deletion of Adar1 led to accumulation of endogenous Z-RNA in mouse embryo fibroblasts (MEFs) and other mouse cells. Adar1 repressed Ifn (see <a href="/entry/147640">147640</a>)-stimulated Z-RNAs formed within the 3-prime UTRs of mRNAs from Ifn-stimulated genes; the repression by Adar1 was completed through direct sequestration and required its functional Z-alpha domain. Accumulation of Z-RNAs resulted from the activation of Zbp1 (<a href="/entry/606750">606750</a>) caused by the loss of Adar1 in the nucleus, leading to Ripk3 (<a href="/entry/605817">605817</a>)-mediated necroptosis in MEFs. The authors identified CBL0137 as a compound that induced Z-DNA formation in mammalian genomic DNA. Z-DNA, however, shares almost-identical structures with Z-RNA, and both Z-DNA and Z-RNA bind ZBP1. Treatment with CBL0137 activated Zbp1 and led to Z-DNA formation followed by Zbp1-dependent rupture of the nuclear envelope, resulting in nuclear necroptosis in wildtype MEFs, similar to Adar1 loss-induced Zbp1 activation and necroptosis. Analysis with tumor fibroblasts revealed that CBL0137 treatment also induced rampant Z-DNA formation and ZBP1-dependent necroptosis. Furthermore, CBL0137 reversed immune checkpoint blockade (ICB) resistance by inducing ZBP1-initiated necroptosis, thus demonstrating that ADAR1 repressed endogenous Z-RNAs by inhibiting ZBP1, and identifying ZBP1-mediated necroptosis as a new determinant of tumor immunogenicity masked by ADAR1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35614224" 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="#21" class="mim-tip-reference" title="Wang, Y., Zeng, Y., Murray, J. M., Nishikura, K. <strong>Genomic organization and chromosomal location of the human dsRNA adenosine deaminase gene: the enzyme for glutamate-activated ion channel RNA editing.</strong> J. Molec. Biol. 254: 184-195, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7490742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7490742</a>] [<a href="https://doi.org/10.1006/jmbi.1995.0610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7490742">Wang et al. (1995)</a> found that the DRADA gene spans 30 kb and contains 15 exons. Transcription of the DRADA gene is initiated at multiple sites, 164 to 216 nucleotides upstream of the translation initiation codon. This nuclear-localized enzyme is involved in the RNA editing required for the expression of certain subtypes of glutamate-gated ion channel subunits. Knowledge of gene structure and sequence should facilitate study of involvement of DRADA in hereditary diseases that may be the result of malfunction of glutamate-gated ion channels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7490742" 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>Using cloned probes on Southern blots of DNA from a panel of rodent-human somatic cell hybrids, <a href="#22" class="mim-tip-reference" title="Wathelet, M. G., Szpirer, J., Nols, C. B., Clauss, I. M., De Wit, L., Islam, M. Q., Levan, G., Horisberger, M. A., Content, J., Szpirer, C., Huez, G. A. <strong>Cloning and chromosomal location of human genes inducible by type I interferon.</strong> Somat. Cell Molec. Genet. 14: 415-426, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3175763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3175763</a>] [<a href="https://doi.org/10.1007/BF01534709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3175763">Wathelet et al. (1988)</a> assigned the IFI4 (ADAR) gene to chromosome 1. (At the Human Gene Mapping Workshop 10 in New Haven in 1989, a system of gene designation was initiated: G = gene; 1 = chromosome number; P = protein; 1 = consecutive gene of this category assigned to this chromosome. Thus the temporary symbol for this protein of unknown function was G1P1.) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3175763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By fluorescence in situ hybridization, <a href="#23" class="mim-tip-reference" title="Weier, H.-U. G., George, C. X., Greulich, K. M., Samuel, C. E. <strong>The interferon-inducible, double-stranded RNA-specific adenosine deaminase gene (DSRAD) maps to human chromosome 1q21.1-21.2.</strong> Genomics 30: 372-375, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8586444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8586444</a>] [<a href="https://doi.org/10.1006/geno.1995.0034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8586444">Weier et al. (1995)</a> mapped the DSRAD gene to 1q21.1-q21.2, centromeric to the marker D1S1705. <a href="#21" class="mim-tip-reference" title="Wang, Y., Zeng, Y., Murray, J. M., Nishikura, K. <strong>Genomic organization and chromosomal location of the human dsRNA adenosine deaminase gene: the enzyme for glutamate-activated ion channel RNA editing.</strong> J. Molec. Biol. 254: 184-195, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7490742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7490742</a>] [<a href="https://doi.org/10.1006/jmbi.1995.0610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7490742">Wang et al. (1995)</a> mapped the DRADA gene to 1q21 by fluorescence in situ hybridization. By FISH, <a href="#24" class="mim-tip-reference" title="Weier, H.-U. G., George, C. X., Lersch, R. A., Breitweser, S., Cheng, J.-F., Samuel, C. E. <strong>Assignment of the RNA-specific adenosine deaminase gene (Adar) to mouse chromosome 3F2 by in situ hybridization.</strong> Cytogenet. Cell Genet. 89: 214-215, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10965125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10965125</a>] [<a href="https://doi.org/10.1159/000015615" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10965125">Weier et al. (2000)</a> mapped the mouse homolog (Adar) to chromosome 3F2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7490742+10965125+8586444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By genomic sequence analysis, <a href="#17" class="mim-tip-reference" title="Scott, A. F. <strong>Personal Communication.</strong> Baltimore, Md. 12/31/2007."None>Scott (2007)</a> determined that the IFI4 gene and the ADAR gene are identical.</p>
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Patients with dyschromatosis symmetrica hereditaria (DSH; <a href="/entry/127400">127400</a>) have pinpoint, pea-sized hyperpigmented and hypopigmented macules on the backs of their hands and the tops of their feet. The face is spared apart from a few scattered small discrete pigmented macules. These abnormalities are asymptomatic and do not affect the general health of the patient. <a href="#13" class="mim-tip-reference" title="Miyamura, Y., Suzuki, T., Kono, M., Inagaki, K., Ito, S., Suzuki, N., Tomita, Y. <strong>Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria.</strong> Am. J. Hum. Genet. 73: 693-699, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12916015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12916015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12916015[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12916015">Miyamura et al. (2003)</a> mapped a locus for DSH to chromosome 1q21.3 where the DSRAD gene is located. In affected members of 4 families segregating DSH, <a href="#13" class="mim-tip-reference" title="Miyamura, Y., Suzuki, T., Kono, M., Inagaki, K., Ito, S., Suzuki, N., Tomita, Y. <strong>Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria.</strong> Am. J. Hum. Genet. 73: 693-699, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12916015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12916015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12916015[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12916015">Miyamura et al. (2003)</a> identified heterozygosity for mutations in the DSRAD gene (<a href="#0001">146920.0001</a>-<a href="#0004">146920.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12916015" 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="#13" class="mim-tip-reference" title="Miyamura, Y., Suzuki, T., Kono, M., Inagaki, K., Ito, S., Suzuki, N., Tomita, Y. <strong>Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria.</strong> Am. J. Hum. Genet. 73: 693-699, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12916015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12916015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12916015[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12916015">Miyamura et al. (2003)</a> commented on the fact that heterozygosity for the Dsrad knockout causes embryonic lethality in mice (<a href="#20" class="mim-tip-reference" title="Wang, Q., Khillan, J., Gadue, P., Nishikura, K. <strong>Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis.</strong> Science 290: 1765-1768, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099415</a>] [<a href="https://doi.org/10.1126/science.290.5497.1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099415">Wang et al., 2000</a>), whereas patients heterozygous for the orthologous human gene have DSH, a disorder with a good prognosis. DSRAD is ubiquitously expressed in the skin; the reason the skin lesions are localized specifically on the backs of hands and on tops of the feet was unknown. <a href="#13" class="mim-tip-reference" title="Miyamura, Y., Suzuki, T., Kono, M., Inagaki, K., Ito, S., Suzuki, N., Tomita, Y. <strong>Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria.</strong> Am. J. Hum. Genet. 73: 693-699, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12916015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12916015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12916015[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12916015">Miyamura et al. (2003)</a> speculated that when melanoblasts migrate from the neural crest to the skin during development, a greater reduction in DSRAD activity might occur at anatomic sites distant from the neural crest. Failure of correct RNA editing may induce the differentiation of melanoblasts to hyperactive or hypoactive melanocytes, then colonizing in an irregular distribution in the skin lesions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11099415+12916015" 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 6 Chinese multigeneration families and 2 sporadic patients with DSH, <a href="#27" class="mim-tip-reference" title="Zhang, X.-J., He, P.-P., Li, M., He, C.-D., Yan, K.-L., Cui, Y., Yang, S., Zhang, K.-Y., Gao, M., Chen, J.-J., Li, C.-R., Jin, L., Chen, H.-D., Xu, S.-J., Huang, W. <strong>Seven novel mutations of the ADAR gene in Chinese families and sporadic patients with dyschromatosis symmetrica hereditaria.</strong> Hum. Mutat. 23: 629-630, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146470</a>] [<a href="https://doi.org/10.1002/humu.9246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146470">Zhang et al. (2004)</a> identified 7 novel heterozygous mutations in the ADAR gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146470" 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 22-year-old Japanese woman who had DSH associated with dystonia, mental deterioration, and intracranial calcifications, <a href="#19" class="mim-tip-reference" title="Tojo, K., Sekijima, Y., Suzuki, T., Suzuki, N., Tomita, Y., Yoshida, K., Hashimoto, T., Ikeda, S. <strong>Dystonia, mental deterioration, and dyschromatosis symmetrica hereditaria in a family with ADAR1 mutation.</strong> Mov. Disord. 21: 1510-1513, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16817193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16817193</a>] [<a href="https://doi.org/10.1002/mds.21011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16817193">Tojo et al. (2006)</a> identified heterozygosity for a missense mutation in the ADAR gene (G1007R; <a href="#0011">146920.0011</a>). Her unaffected mother and sister did not carry the mutation; DNA was unavailable from her affected deceased father. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16817193" 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 Taiwanese woman with DSH, <a href="#3" class="mim-tip-reference" title="Chao, S.-C., Huang, C.-Y., Yang, M.-H. <strong>A novel nonsense mutation of the DSRAD gene in a Taiwanese family with dyschromatosis symmetrica hereditaria.</strong> Europ. J. Derm. 16: 449-540, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16935814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16935814</a>]" pmid="16935814">Chao et al. (2006)</a> identified heterozygosity for a nonsense mutation in the ADAR gene (Q693X; <a href="#0005">146920.0005</a>) that segregated with disease in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16935814" 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 Chinese family with DSH, <a href="#25" class="mim-tip-reference" title="Xing, Q., Shu, A., Yu, L., Zhang, A., Du, J., Xuan, J., Wang, L., He, G., Meng, J., Li, X., Feng, G., He, L. <strong>Novel deletion mutation of DSRAD in a Chinese family with dyschromatosis symmetrica hereditaria (DSH).</strong> Europ. J. Derm. 17: 247-248, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478391</a>] [<a href="https://doi.org/10.1684/ejd.2007.0161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17478391">Xing et al. (2007)</a> identified heterozygosity for 2-bp deletion (<a href="#0006">146920.0006</a>) in the ADAR gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478391" 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 11-year-old Japanese boy who had DSH associated with dystonia, mental deterioration, and intracranial calcifications, <a href="#10" class="mim-tip-reference" title="Kondo, T., Suzuki, T., Ito, S., Kono, M., Negoro, T., Tomita, Y. <strong>Dyschromatosis symmetrica hereditaria associated with neurological disorders.</strong> J. Derm. 35: 662-666, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19017046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19017046</a>] [<a href="https://doi.org/10.1111/j.1346-8138.2008.00540.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19017046">Kondo et al. (2008)</a> identified heterozygosity for the previously reported G1007R mutation in the ADAR gene (<a href="#0011">146920.0011</a>). His mother, who had skin lesions but no neurologic features, was also heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19017046" 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 12-year-old Chinese girl with DSH and her affected father and paternal grandfather, <a href="#5" class="mim-tip-reference" title="Dong, Y., Xiao, S., Ren, J., Huo, J., Liu, Y., Li, X. <strong>A novel missense mutation of the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria.</strong> Europ. J. Derm. 19: 270-272, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19251566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19251566</a>] [<a href="https://doi.org/10.1684/ejd.2009.0639" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19251566">Dong et al. (2009)</a> sequenced the ADAR gene and identified heterozygosity for an H958R substitution in all 3. The mutation was not found in the proband's unaffected paternal uncle and aunt, or in 50 unrelated Chinese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19251566" 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>Aicardi-Goutieres Syndrome 6</em></strong></p><p>
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<a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> identified 9 mutations in the ADAR1 gene in 10 families with Aicardi-Goutieres syndrome (AGS6; <a href="/entry/615010">615010</a>). The missense mutation pro193 to ala (P193A; <a href="#0007">146920.0007</a>) occurred in 5 families. Two unrelated affected individuals harbored a heterozygous de novo missense mutation, gly1007 to arg (G1007R; <a href="#0011">146920.0011</a>). This mutation appeared to have a dominant-negative effect. Of the 8 amino acid substitutions identified, 7 involved residues situated in the catalytic domain of ADAR1; 5 of these 7 (arg892, lys999, gly1007, tyr1112, and asp1113) lie along the surface of the protein that interacts with double-stranded RNA, and the 2 others (ala870 and ile872) lie internal to the domain structure and are predicted to destabilize the protein. In contrast, pro193 is positioned within the Z-DNA/Z-RNA-binding domain. In the wildtype protein, pro193 makes direct contact with the nucleic acid, and substitution of this residue with alanine removes important atomic interactions between the protein and DNA/RNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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>The recurrent mutation P193A (<a href="#0007">146920.0007</a>) implicates the IFN-inducible p150 isoform of ADAR1 in the Aicardi-Goutieres syndrome phenotype. Mice lacking Adar1 die by around embryonic day 12.5 owing to defective hematopoiesis and widespread apoptosis, which are associated with global upregulation of IFN-stimulated genes, indicating that ADAR1 acts as a suppressor of type I interferon signaling. <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> used whole blood from 8 ADAR1 mutation-positive individuals to perform quantitative RT-PCR to analyze the mRNA levels of 15 IFN-stimulated gene (IsgS). Compared to 9 controls, all tested individuals with mutations in ADAR1, including the 2 individuals harboring the heterozygous de novo gly1007-to-arg (G1007R; <a href="#0011">146920.0011</a>) mutation, showed a consistent pattern of ISG upregulation. <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> analyzed the 6 most highly expressed ISGs in 10 ADAR1 mutation-positive AGS cases, 6 sets of parents with heterozygous mutations, and 18 ADAR1 mutation-positive individuals with DSH. Expression was variably higher in AGS heterozygous parents and DSH cases versus controls, whereas individuals with a clinical diagnosis of AGS (due either to biallelic mutations in ADAR1 or a heterozygous mutation resulting in the G1007R amino-acid substitution) had even higher levels of expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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 7 patients, including 2 sibs, with atypical AGS6, <a href="#12" class="mim-tip-reference" title="Livingston, J. H., Lin, J.-P., Dale, R. C., Gill, D., Brogan, P., Munnich, A., Kurian, M. A., Gonzalez-Martinez, V., De Goede, C. G. E. L., Falconer, A., Forte, G., Jenkinson, E. M., Kasher, P. R., Szynkiewicz, M., Rice, G. I., Crow, Y. J. <strong>A type I interferon signature identifies bilateral striatal necrosis due to mutations in ADAR1.</strong> J. Med. Genet. 51: 76-82, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24262145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24262145</a>] [<a href="https://doi.org/10.1136/jmedgenet-2013-102038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24262145">Livingston et al. (2014)</a> identified compound heterozygous mutations in the ADAR gene (see, e.g., <a href="#0007">146920.0007</a>, <a href="#0016">146920.0016</a>). Six of the patients carried the P193A mutation on 1 allele. Two additional half-sibs with the disorder were found to carry a heterozygous G1007R missense mutation; the second mutation was likely not detected in these patients. Functional studies of the variants were not performed. These patients were ascertained from a cohort of patients with bilateral striatal necrosis who presented in infancy or early childhood with rapidly progressive severe developmental regression and incapacitating dystonia. Analysis of blood samples showed an upregulation of interferon-stimulated genes. No interferon signature was found in 4 children with a similar disorder who did not have ADAR mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24262145" 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>Role in Innate Immunity</em></strong></p><p>
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Because of the 2 to 10% primary failure rate of measles vaccination and the importance of innate immunity to prevent or reduce viral replication and spread until the adaptive immune response to eliminate the virus, <a href="#6" class="mim-tip-reference" title="Haralambieva, I. H., Ovsyannikova, I. G., Umlauf, B. J., Vierkant, R. A., Pankratz, V. S., Jacobson, R. M., Poland, G. A. <strong>Genetic polymorphisms in host antiviral genes: associations with humoral and cellular immunity to measles vaccine.</strong> Vaccine 29: 8988-8997, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21939710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21939710</a>] [<a href="https://doi.org/10.1016/j.vaccine.2011.09.043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21939710">Haralambieva et al. (2011)</a> performed a comprehensive candidate gene association study in a racially diverse cohort of 745 healthy schoolchildren in Minnesota who had had 2 doses of measles vaccine. Variants within DDX58 (<a href="/entry/609631">609631</a>) were associated with measles-specific antibody variations in Caucasians. Four DDX58 polymorphisms in high linkage disequilibrium were also associated with variations in measles-specific IFNG (<a href="/entry/147570">147570</a>) and IL2 (<a href="/entry/147680">147680</a>) secretion in Caucasians. ADAR variants also had a role in regulating measles-specific IFNG responses in Caucasians. Two intronic OAS1 (<a href="/entry/164350">164350</a>) SNPs were associated with increased neutralizing antibody levels in African Americans. <a href="#6" class="mim-tip-reference" title="Haralambieva, I. H., Ovsyannikova, I. G., Umlauf, B. J., Vierkant, R. A., Pankratz, V. S., Jacobson, R. M., Poland, G. A. <strong>Genetic polymorphisms in host antiviral genes: associations with humoral and cellular immunity to measles vaccine.</strong> Vaccine 29: 8988-8997, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21939710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21939710</a>] [<a href="https://doi.org/10.1016/j.vaccine.2011.09.043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21939710">Haralambieva et al. (2011)</a> concluded that multiple innate immunity genes and genetic variants are likely involved in modulating the adaptive immune response to live attenuated measles vaccine in Caucasians and African Americans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21939710" 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="#20" class="mim-tip-reference" title="Wang, Q., Khillan, J., Gadue, P., Nishikura, K. <strong>Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis.</strong> Science 290: 1765-1768, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099415</a>] [<a href="https://doi.org/10.1126/science.290.5497.1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099415">Wang et al. (2000)</a> knocked out the Adar1 gene in mice by targeted disruption and found that heterozygosity for the Adar1 knockout causes embryonic lethality. To understand the mechanism of embryonic lethality, they studied staged chimeric mouse embryos with a high contribution from embryonic stem cells with a functional null allele for Adar1. No live chimeric embryo with a high degree of contribution by Adar1 +/- cells was recovered beyond embryonic day (E) 14.5. The primary defects were in the hematopoietic system, with a large number of nucleated erythrocytes in chimeric mice. Adar1 expression normally increases at E13 to E14 in the liver. Based on these results, <a href="#20" class="mim-tip-reference" title="Wang, Q., Khillan, J., Gadue, P., Nishikura, K. <strong>Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis.</strong> Science 290: 1765-1768, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11099415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11099415</a>] [<a href="https://doi.org/10.1126/science.290.5497.1765" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11099415">Wang et al. (2000)</a> concluded that a regulated increase in Adra1 expression in liver is required at E12 and E13. Failure to increase Adar1 may result in underediting of the RNA of currently unknown target genes, which in turn affects proliferation and/or differentiation of erythrocytes. Thus, regulated levels of ADAR expression appear to be critical for embryonic erythropoiesis in the liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11099415" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=146920[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<a id="0001" class="mim-anchor"></a>
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<strong>.0001 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</strong>
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ADAR, ARG474TER
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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> rs121912421 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912421;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/rs121912421?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=rs121912421" 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=rs121912421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015940 OR RCV003764577" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015940, RCV003764577" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015940...</a>
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<span class="mim-text-font">
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<p>In a Japanese family with autosomal dominant dyschromatosis symmetrica hereditaria (DSH; <a href="/entry/127400">127400</a>) in members of 4 successive generations, <a href="#13" class="mim-tip-reference" title="Miyamura, Y., Suzuki, T., Kono, M., Inagaki, K., Ito, S., Suzuki, N., Tomita, Y. <strong>Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria.</strong> Am. J. Hum. Genet. 73: 693-699, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12916015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12916015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12916015[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12916015">Miyamura et al. (2003)</a> identified a CGA-to-TGA transition in exon 2 of the DSRAD gene, resulting in a nonsense change, arg474 to stop (R474X). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12916015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0002" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0002 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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ADAR, LEU923PRO
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28936680 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28936680;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=rs28936680" 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=rs28936680" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015941" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015941" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015941</a>
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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 Japanese family with dyschromatosis symmetrica hereditaria (DSH; <a href="/entry/127400">127400</a>) in members of 4 successive generations, <a href="#13" class="mim-tip-reference" title="Miyamura, Y., Suzuki, T., Kono, M., Inagaki, K., Ito, S., Suzuki, N., Tomita, Y. <strong>Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria.</strong> Am. J. Hum. Genet. 73: 693-699, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12916015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12916015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12916015[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12916015">Miyamura et al. (2003)</a> demonstrated that affected members were heterozygous for a CTC-to-CCC transition in exon 10 of the DSRAD gene, resulting in a leu923-to-pro (L923P) amino acid change. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12916015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0003" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0003 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</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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<div style="float: left;">
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ADAR, LYS952TER
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912422 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912422;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=rs121912422" 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=rs121912422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015942" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015942" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015942</a>
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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 Japanese family with autosomal dominant dyschromatosis symmetrica hereditaria (DSH; <a href="/entry/127400">127400</a>) in 4 generations, <a href="#13" class="mim-tip-reference" title="Miyamura, Y., Suzuki, T., Kono, M., Inagaki, K., Ito, S., Suzuki, N., Tomita, Y. <strong>Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria.</strong> Am. J. Hum. Genet. 73: 693-699, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12916015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12916015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12916015[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12916015">Miyamura et al. (2003)</a> demonstrated an AAA-to-TAA transversion in exon 10 of the DSRAD gene, resulting in a lys952-to-stop (K952X) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12916015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0004" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0004 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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ADAR, PHE1165SER
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</span>
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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> rs28936681 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28936681;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/rs28936681?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=rs28936681" 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=rs28936681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015943" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015943" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015943</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a Japanese family with autosomal dominant dyschromatosis symmetrica hereditaria (DSH; <a href="/entry/127400">127400</a>) in 5 successive generations, <a href="#13" class="mim-tip-reference" title="Miyamura, Y., Suzuki, T., Kono, M., Inagaki, K., Ito, S., Suzuki, N., Tomita, Y. <strong>Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria.</strong> Am. J. Hum. Genet. 73: 693-699, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12916015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12916015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12916015[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/378209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12916015">Miyamura et al. (2003)</a> identified a TTT-to-TCT transition in exon 15 of the DSRAD gene, resulting in a phe1165-to-ser (F1165S) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12916015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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ADAR, GLN693TER
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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> rs121912423 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912423;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/rs121912423?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=rs121912423" 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=rs121912423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015944" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015944" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015944</a>
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</span>
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<span class="mim-text-font">
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<p>In a Taiwanese woman with dyschromatosis symmetrica hereditaria (DSH; <a href="/entry/127400">127400</a>), <a href="#3" class="mim-tip-reference" title="Chao, S.-C., Huang, C.-Y., Yang, M.-H. <strong>A novel nonsense mutation of the DSRAD gene in a Taiwanese family with dyschromatosis symmetrica hereditaria.</strong> Europ. J. Derm. 16: 449-540, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16935814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16935814</a>]" pmid="16935814">Chao et al. (2006)</a> identified a 2077C-T transition in exon 5 of the ADAR gene, resulting in a gln693-to-ter (Q693X) substitution. The mutation was also found in her affected sister and daughter but not in unaffected members of the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16935814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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ADAR, 2-BP DEL, 941CT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906541 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906541;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=rs387906541" 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=rs387906541" 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=RCV000015945" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015945" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015945</a>
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<p>In affected members of a large 5-generation Chinese family with dyschromatosis symmetrica hereditaria (DSH; <a href="/entry/127400">127400</a>), <a href="#25" class="mim-tip-reference" title="Xing, Q., Shu, A., Yu, L., Zhang, A., Du, J., Xuan, J., Wang, L., He, G., Meng, J., Li, X., Feng, G., He, L. <strong>Novel deletion mutation of DSRAD in a Chinese family with dyschromatosis symmetrica hereditaria (DSH).</strong> Europ. J. Derm. 17: 247-248, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478391</a>] [<a href="https://doi.org/10.1684/ejd.2007.0161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17478391">Xing et al. (2007)</a> identified a 2-bp deletion (941delCT) in exon 2 of the ADAR gene, resulting in a frameshift and premature termination of the protein. The family was from Hunan province. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478391" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs145588689 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs145588689;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/rs145588689?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=rs145588689" 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=rs145588689" 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=RCV000114336 OR RCV000255775 OR RCV000288094 OR RCV000352411 OR RCV000548694 OR RCV000624331 OR RCV000778185" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000114336, RCV000255775, RCV000288094, RCV000352411, RCV000548694, RCV000624331, RCV000778185" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000114336...</a>
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<p>In 5 families of European descent with Aicardi-Goutieres syndrome (AGS6; <a href="/entry/615010">615010</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> identified a heterozygous C-to-G transversion at nucleotide 577 in exon 2 of the ADAR gene, resulting in a pro-to-ala substitution at codon 193 (P193A). In 2 of these families, one Norwegian and the other Spanish, the mutation occurred in compound heterozygosity with an arg892-to-his mutation (<a href="#0008">146920.0008</a>). The other 3 families respectively carried the P193A mutation in compound heterozygosity with A870T (<a href="#0009">146920.0009</a>), I872T (<a href="#0014">146920.0014</a>), and a 5-bp deletion (<a href="#0015">146920.0015</a>). Proline-293 is highly evolutionarily conserved and positioned within the Z-DNA/Z-RNA-binding domain. This variant was also observed in 41 subjects (32 of 4,350 European Americans and 9 of 2,203 African Americans) in the Exome Variant Server database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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 patients, including 2 sibs, with atypical AGS6, <a href="#12" class="mim-tip-reference" title="Livingston, J. H., Lin, J.-P., Dale, R. C., Gill, D., Brogan, P., Munnich, A., Kurian, M. A., Gonzalez-Martinez, V., De Goede, C. G. E. L., Falconer, A., Forte, G., Jenkinson, E. M., Kasher, P. R., Szynkiewicz, M., Rice, G. I., Crow, Y. J. <strong>A type I interferon signature identifies bilateral striatal necrosis due to mutations in ADAR1.</strong> J. Med. Genet. 51: 76-82, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24262145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24262145</a>] [<a href="https://doi.org/10.1136/jmedgenet-2013-102038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24262145">Livingston et al. (2014)</a> identified the P193A mutation in compound heterozygosity with another pathogenic ARAR mutation (see, e.g., I872T and R544XC, <a href="#0016">146920.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24262145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs398122892 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122892;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/rs398122892?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=rs398122892" 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=rs398122892" 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=RCV000032650 OR RCV003764649" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032650, RCV003764649" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032650...</a>
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<p>In patients from a Norwegian and a Spanish family, respectively, with Aicardi-Goutieres syndrome-6 (AGS6; <a href="/entry/615010">615010</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> identified compound heterozygosity for mutations in the ADAR gene, a P193A mutation (<a href="#0007">146920.0007</a>) and a G-to-A transition at nucleotide 2675 in exon 9, resulting in an arg-to-his substitution at codon 892 (R892H). The patients from the Spanish family were identical twins. The R892H mutation was not observed in over 12,000 control alleles in the Exome Variant Server database. An arginine at position 892 in this gene is evolutionarily invariant to C. elegans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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">rs398122893 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122893;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=rs398122893" 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=rs398122893" 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=RCV000032651" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032651" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032651</a>
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<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; <a href="/entry/615010">615010</a>) from an Italian family, <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> found compound heterozygosity for the P193A mutation (<a href="#0007">146920.0007</a>) in ADAR and a G-to-A transition at nucleotide 2608 in exon 8, resulting in an ala-to-thr substitution at codon 870 (A870T). This mutation was not identified among the 12,000 control alleles within the Exome Variant Server database. An alanine at position 870 in this gene is evolutionarily invariant through C. elegans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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">rs398122894 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122894;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=rs398122894" 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=rs398122894" 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=RCV000032652" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032652" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032652</a>
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<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; <a href="/entry/615010">615010</a>) from a consanguineous Pakistani family, <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> identified homozygosity for a G-to-C transversion at nucleotide 3337 in exon 14 of the ADAR gene, resulting in an asp-to-his substitution at codon 1113 (D1113H). Both parents were heterozygous and this mutation was not identified in the Exome Variant Server database. An aspartic acid at position 1113 in this gene is evolutionarily invariant through C. elegans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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">rs398122822 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122822;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=rs398122822" 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=rs398122822" 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=RCV000032653 OR RCV000032654 OR RCV000762850 OR RCV001091722" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032653, RCV000032654, RCV000762850, RCV001091722" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032653...</a>
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<p><strong><em>Dyschromatosis Symmetrica Hereditaria</em></strong></p><p>
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In a 22-year-old Japanese woman with dyschromatosis symmetrica hereditaria (DSH; <a href="/entry/127400">127400</a>) associated with dystonia, mental deterioration, and tissue calcification, <a href="#19" class="mim-tip-reference" title="Tojo, K., Sekijima, Y., Suzuki, T., Suzuki, N., Tomita, Y., Yoshida, K., Hashimoto, T., Ikeda, S. <strong>Dystonia, mental deterioration, and dyschromatosis symmetrica hereditaria in a family with ADAR1 mutation.</strong> Mov. Disord. 21: 1510-1513, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16817193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16817193</a>] [<a href="https://doi.org/10.1002/mds.21011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16817193">Tojo et al. (2006)</a> identified heterozygosity for a c.3019G-A transition in exon 11 of the ADAR gene, resulting in a gly1007-to-arg (G1007R) substitution. Her unaffected mother and sister did not carry the mutation; DNA was unavailable from her affected deceased father. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16817193" 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 11-year-old Japanese boy with DSH and dystonia, mental deterioration, and brain calcification, <a href="#10" class="mim-tip-reference" title="Kondo, T., Suzuki, T., Ito, S., Kono, M., Negoro, T., Tomita, Y. <strong>Dyschromatosis symmetrica hereditaria associated with neurological disorders.</strong> J. Derm. 35: 662-666, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19017046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19017046</a>] [<a href="https://doi.org/10.1111/j.1346-8138.2008.00540.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19017046">Kondo et al. (2008)</a> identified heterozygosity for the previously reported G1007R substitution in the ADAR gene. His mother, who had skin lesions but no neurologic features, was also heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19017046" 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>Aicardi-Goutieres Syndrome</em></strong></p><p>
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In 2 individuals, 1 of Brazilian origin and 1 of European American origin, with Aicardi-Goutieres syndrome-6 (AGS6; <a href="/entry/615010">615010</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> identified a heterozygous de novo mutation in exon 11 of the ADAR gene: a G-to-A transition at nucleotide 3019, resulting in a gly-to-arg substitution at codon 1007 (G1007R). Using an ADAR1 editing substrate, miR376-a2 (<a href="/entry/610960">610960</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> found that, of 6 ADAR mutations tested, only the G1007R variant showed a significant effect on editing, with levels of editing equivalent to those seen with inactive protein. The proximity of G1007R to the RNA backbone and the possibility for an arginine residue to make polymorphic interactions there suggested a mechanism whereby arg1007 might confer a dominant-negative effect: by binding more tightly to RNA the mutant protein could act as a competitive inhibitor of wildtype protein while being itself catalytically inactive. <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> found that a plasmid expressing G1007R ADAR1 showed stronger inhibition of wildtype ADAR1 than equivalent amounts of a plasmid expressing catalytically inactive ADAR1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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 half-sibs with AGS6, <a href="#12" class="mim-tip-reference" title="Livingston, J. H., Lin, J.-P., Dale, R. C., Gill, D., Brogan, P., Munnich, A., Kurian, M. A., Gonzalez-Martinez, V., De Goede, C. G. E. L., Falconer, A., Forte, G., Jenkinson, E. M., Kasher, P. R., Szynkiewicz, M., Rice, G. I., Crow, Y. J. <strong>A type I interferon signature identifies bilateral striatal necrosis due to mutations in ADAR1.</strong> J. Med. Genet. 51: 76-82, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24262145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24262145</a>] [<a href="https://doi.org/10.1136/jmedgenet-2013-102038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24262145">Livingston et al. (2014)</a> found the G1007R mutation in heterozygosity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24262145" 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 5-year-old boy, born of unrelated Hispanic parents, with onset of nonsyndromic spastic paraplegia at age 2 years following normal psychomotor development, <a href="#4" class="mim-tip-reference" title="Crow, Y. J., Zaki, M. S., Abdel-Hamid, M. S., Abdel-Salam, G., Boespflug-Tanguy, O., Cordeiro, N. J. V., Gleeson, J. G., Gowrinathan, N. R., Laugel, V., Renaldo, F., Rodriguez, D., Livingston, J. H., Rice, G. I. <strong>Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia.</strong> Neuropediatrics 45: 386-391, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25243380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25243380</a>] [<a href="https://doi.org/10.1055/s-0034-1389161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25243380">Crow et al. (2014)</a> identified a de novo heterozygous G1007R mutation in the ADAR1 gene. The mutation was found by exome sequencing and confirmed by Sanger sequencing. Brain imaging and cognition were normal, and laboratory studies showed increased interferon. <a href="#4" class="mim-tip-reference" title="Crow, Y. J., Zaki, M. S., Abdel-Hamid, M. S., Abdel-Salam, G., Boespflug-Tanguy, O., Cordeiro, N. J. V., Gleeson, J. G., Gowrinathan, N. R., Laugel, V., Renaldo, F., Rodriguez, D., Livingston, J. H., Rice, G. I. <strong>Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia.</strong> Neuropediatrics 45: 386-391, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25243380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25243380</a>] [<a href="https://doi.org/10.1055/s-0034-1389161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25243380">Crow et al. (2014)</a> emphasized the emerging phenotypic variability associated with AGS, noting that neurologic dysfunction is not always marked in this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25243380" 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">rs398122895 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122895;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=rs398122895" 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=rs398122895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; <a href="/entry/615010">615010</a>) from a consanguineous Pakistani family, <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> identified homozygosity for an A-to-T transversion at nucleotide 3335 in exon 14 of the ADAR gene, resulting in a tyr-to-phe substitution at codon 1112 (Y1112F). This mutation was not identified among 12,000 control alleles in the Exome Variant Server database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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">rs398122896 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122896;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=rs398122896" 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=rs398122896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; <a href="/entry/615010">615010</a>) from a nonconsanguineous Indian family, <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> identified a homozygous G-to-T transversion at nucleotide 2997 in exon 11 of the ADAR gene, resulting in a lys-to-asn substitution at codon 999 (K999N). Both parents were carriers of the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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>.0014 AICARDI-GOUTIERES SYNDROME 6</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> rs398122897 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122897;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/rs398122897?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=rs398122897" 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=rs398122897" 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=RCV000032657" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032657" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032657</a>
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<p>In a patient of Caucasian British origin with Aicardi-Goutieres syndrome-6 (AGS6; <a href="/entry/615010">615010</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> identified compound heterozygosity for the pro193-to-ala (P193A; <a href="#0007">146920.0007</a>) mutation in the ADAR gene and a T-to-C transition at nucleotide 2615 in exon 8, resulting in an ile-to-thr substitution at codon 872 (I872T; <a href="#0014">146920.0014</a>). This mutation involving an evolutionarily conserved residue was not identified in 12,000 control samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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>.0015 AICARDI-GOUTIERES SYNDROME 6</strong>
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ADAR, 5-BP DEL, NT1076
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs398122898 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122898;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=rs398122898" 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=rs398122898" 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=RCV000032658" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032658" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032658</a>
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<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; <a href="/entry/615010">615010</a>) from an Italian family, <a href="#16" class="mim-tip-reference" title="Rice, G. I., Kasher, P. R., Forte, G. M. A., Mannion, N. M., Greenwood, S. M., Szynkiewicz, M., Dickerson, J. E., Bhaskar, S. S., Zampini, M., Briggs, T. A., Jenkinson, E. M., Bacino, C. A., and 42 others. <strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong> Nature Genet. 44: 1243-1248, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001123</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23001123[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/10.1038/ng.2414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001123">Rice et al. (2012)</a> identified a heterozygous 5-bp deletion in the ADAR gene (1076_1080del) that resulted in frameshift and premature termination (Lys359ArgfsTer14). The patient was compound heterozygous for the P193A mutation (see <a href="#0007">146920.0007</a>). The frameshift mutation was not identified among 12,000 control alleles in the Exome Variant Server database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001123" 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>.0016 AICARDI-GOUTIERES SYNDROME 6</strong>
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ADAR, ARG544TER
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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> rs768943773 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs768943773;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/rs768943773?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=rs768943773" 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=rs768943773" 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=RCV000114429" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000114429" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000114429</a>
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<p>In 2 Caucasian sibs with atypical Aicardi-Goutieres syndrome-6 (AGS6; <a href="/entry/615010">615010</a>), <a href="#12" class="mim-tip-reference" title="Livingston, J. H., Lin, J.-P., Dale, R. C., Gill, D., Brogan, P., Munnich, A., Kurian, M. A., Gonzalez-Martinez, V., De Goede, C. G. E. L., Falconer, A., Forte, G., Jenkinson, E. M., Kasher, P. R., Szynkiewicz, M., Rice, G. I., Crow, Y. J. <strong>A type I interferon signature identifies bilateral striatal necrosis due to mutations in ADAR1.</strong> J. Med. Genet. 51: 76-82, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24262145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24262145</a>] [<a href="https://doi.org/10.1136/jmedgenet-2013-102038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24262145">Livingston et al. (2014)</a> identified compound heterozygosity for 2 mutations in the ADAR gene: a c.1630C-T transition in exon 3, resulting in an arg544-to-ter (R544X) substitution, and P193A (<a href="#0007">146920.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24262145" 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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Agranat, L., Raitskin, O., Sperling, J., Sperling, R.
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<strong>The editing enzyme ADAR1 and the mRNA surveillance protein hUpf1 interact in the cell nucleus.</strong>
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Proc. Nat. Acad. Sci. 105: 5028-5033, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18362360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18362360</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18362360[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18362360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0710576105" target="_blank">Full Text</a>]
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Bass, B. L., Weintraub, H.
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<strong>An unwinding activity that covalently modifies its double-stranded RNA substrate.</strong>
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Cell 55: 1089-1098, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3203381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3203381</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3203381" 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/10.1016/0092-8674(88)90253-x" target="_blank">Full Text</a>]
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Chao, S.-C., Huang, C.-Y., Yang, M.-H.
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<strong>A novel nonsense mutation of the DSRAD gene in a Taiwanese family with dyschromatosis symmetrica hereditaria.</strong>
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Europ. J. Derm. 16: 449-540, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16935814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16935814</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16935814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Crow, Y. J., Zaki, M. S., Abdel-Hamid, M. S., Abdel-Salam, G., Boespflug-Tanguy, O., Cordeiro, N. J. V., Gleeson, J. G., Gowrinathan, N. R., Laugel, V., Renaldo, F., Rodriguez, D., Livingston, J. H., Rice, G. I.
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<strong>Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia.</strong>
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Neuropediatrics 45: 386-391, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25243380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25243380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25243380" 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/10.1055/s-0034-1389161" target="_blank">Full Text</a>]
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Dong, Y., Xiao, S., Ren, J., Huo, J., Liu, Y., Li, X.
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<strong>A novel missense mutation of the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria.</strong>
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Europ. J. Derm. 19: 270-272, 2009.
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<a id="22" class="mim-anchor"></a>
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<a id="Wathelet1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wathelet, M. G., Szpirer, J., Nols, C. B., Clauss, I. M., De Wit, L., Islam, M. Q., Levan, G., Horisberger, M. A., Content, J., Szpirer, C., Huez, G. A.
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|
<strong>Cloning and chromosomal location of human genes inducible by type I interferon.</strong>
|
|
Somat. Cell Molec. Genet. 14: 415-426, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3175763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3175763</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3175763" 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/BF01534709" 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="Weier1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weier, H.-U. G., George, C. X., Greulich, K. M., Samuel, C. E.
|
|
<strong>The interferon-inducible, double-stranded RNA-specific adenosine deaminase gene (DSRAD) maps to human chromosome 1q21.1-21.2.</strong>
|
|
Genomics 30: 372-375, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8586444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8586444</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8586444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1995.0034" 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="24" class="mim-anchor"></a>
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<a id="Weier2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weier, H.-U. G., George, C. X., Lersch, R. A., Breitweser, S., Cheng, J.-F., Samuel, C. E.
|
|
<strong>Assignment of the RNA-specific adenosine deaminase gene (Adar) to mouse chromosome 3F2 by in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 89: 214-215, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10965125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10965125</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10965125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000015615" target="_blank">Full Text</a>]
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</p>
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</li>
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<li>
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<a id="25" class="mim-anchor"></a>
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<a id="Xing2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Xing, Q., Shu, A., Yu, L., Zhang, A., Du, J., Xuan, J., Wang, L., He, G., Meng, J., Li, X., Feng, G., He, L.
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<strong>Novel deletion mutation of DSRAD in a Chinese family with dyschromatosis symmetrica hereditaria (DSH).</strong>
|
|
Europ. J. Derm. 17: 247-248, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478391/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478391</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478391" 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/10.1684/ejd.2007.0161" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="26" class="mim-anchor"></a>
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<a id="Zhang2022" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, T., Yin, C., Fedorov, A., Qiao, L., Bao, H., Beknazarov, N., Wang, S., Gautam, A., Williams, R. M., Crawford, J. C., Peri, S., Studitsky, V., Beg, A. A., Thomas, P. G., Walkley, C., Xu, Y., Poptsova, M., Herbert, A., Balachandran, S.
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<strong>ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis.</strong>
|
|
Nature 606: 594-602, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35614224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35614224</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35614224[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35614224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41586-022-04753-7" 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="27" class="mim-anchor"></a>
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<a id="Zhang2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, X.-J., He, P.-P., Li, M., He, C.-D., Yan, K.-L., Cui, Y., Yang, S., Zhang, K.-Y., Gao, M., Chen, J.-J., Li, C.-R., Jin, L., Chen, H.-D., Xu, S.-J., Huang, W.
|
|
<strong>Seven novel mutations of the ADAR gene in Chinese families and sporadic patients with dyschromatosis symmetrica hereditaria.</strong>
|
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Hum. Mutat. 23: 629-630, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146470</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.9246" 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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Marla J. F. O'Neill - updated : 06/13/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 03/28/2024<br>Ada Hamosh - updated : 03/05/2019<br>Ada Hamosh - updated : 12/21/2017<br>Ada Hamosh - updated : 12/10/2015<br>Cassandra L. Kniffin - updated : 12/15/2014<br>Cassandra L. Kniffin - updated : 4/9/2014<br>Ada Hamosh - updated : 1/9/2013<br>Paul J. Converse - updated : 7/20/2012<br>Patricia A. Hartz - updated : 6/5/2008
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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 : 6/16/1989
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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 : 06/13/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 03/28/2024<br>carol : 10/14/2019<br>alopez : 03/05/2019<br>alopez : 12/21/2017<br>carol : 04/29/2017<br>carol : 04/28/2017<br>alopez : 12/10/2015<br>alopez : 12/18/2014<br>mcolton : 12/16/2014<br>mcolton : 12/16/2014<br>ckniffin : 12/15/2014<br>alopez : 4/15/2014<br>ckniffin : 4/9/2014<br>carol : 9/18/2013<br>alopez : 9/10/2013<br>alopez : 1/11/2013<br>alopez : 1/10/2013<br>alopez : 1/10/2013<br>terry : 1/9/2013<br>mgross : 7/20/2012<br>alopez : 6/25/2008<br>terry : 6/5/2008<br>carol : 1/2/2008<br>alopez : 11/11/1998<br>carol : 8/17/1998<br>jason : 6/16/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>supermim : 2/3/1990<br>ddp : 10/27/1989<br>root : 9/23/1989
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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> 146920
|
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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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ADENOSINE DEAMINASE, RNA-SPECIFIC; ADAR
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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ADENOSINE DEAMINASE, RNA-SPECIFIC, 1; ADAR1<br />
|
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DOUBLE-STRANDED RNA-SPECIFIC ADENOSINE DEAMINASE; DSRAD; DRADA<br />
|
|
INTERFERON-INDUCED PROTEIN 4; IFI4<br />
|
|
G1P1
|
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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: ADAR</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 239085000;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
|
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<em>
|
|
Cytogenetic location: 1q21.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 1:154,582,057-154,627,997 </span>
|
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</em>
|
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</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">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<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
|
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
|
<tbody>
|
|
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<tr>
|
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<td rowspan="2">
|
|
<span class="mim-font">
|
|
1q21.3
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Aicardi-Goutieres syndrome 6
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
615010
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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">
|
|
Dyschromatosis symmetrica hereditaria
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
127400
|
|
</span>
|
|
</td>
|
|
<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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</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>
|
|
</h4>
|
|
|
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Double-stranded RNA-specific adenosine deaminase (DSRAD), or RNA-specific adenosine deaminase (ADAR), was identified as a developmentally regulated dsRNA unwinding activity in early antisense experiments with Xenopus oocytes (Bass and Weintraub, 1988). The enzyme converts adenosine to inosine in dsRNA, which destabilizes the dsRNA helix. The RNA modifying activity of DSRAD is important for various functions. Among these are site-specific RNA editing of transcripts of the glutamate receptors (see 138248), which are channels for the neurotransmitter L-glutamate in the brain. DSRAD also functions to modify viral RNA genomes and may be responsible for hypermutation of certain negative-stranded viruses, such as measles, which may result in lethal measles inclusion body encephalitis (Weier et al., 1995). </p>
|
|
</span>
|
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<div>
|
|
<br />
|
|
</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
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<span class="mim-text-font">
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<p>Kim et al. (1994) cloned a human gene for double-stranded RNA adenosine deaminase using degenerate PCR with primers based on partial bovine amino acid sequence. A cDNA was obtained from a human natural killer cell library. </p><p>From an interferon-alpha (IFNA1; 147660)-treated human amnion U cell line, Patterson and Samuel (1995) cloned ADAR, which they designated K88. The 5-prime end of the transcript, including part of the coding region, is GC-rich and the 3-prime untranslated region (UTR) contains 3 motifs associated with RNA instability. The deduced 1,226-amino acid protein has a calculated molecular mass of 136 kD. It has 2 N-terminal repeats of a 26-amino acid sequence that displayed 31% identity (58% similarity) with the N-terminal region of vaccinia virus E3L protein. Between these 2 repeats were 2 unique tandem repeats that shared 79% identity (86% similarity) with each other over 49 amino acids. This region is followed by 3 copies of the double-stranded RNA (dsRNA)-binding subdomain R motif, and a conserved C-terminal domain of 380 amino acids. Northern blot analysis detected a 6.7-kb transcript in all tissues examined, including heart, brain, lung, liver, skeletal muscle, kidney, and pancreas, and in human amnion U cells. Western blot analysis detected proteins of 150 and 110 kD in human neuroblastoma and amnion U cell lines. Using domain-specific antibodies, Patterson and Samuel (1995) determined that the 110-kD protein lacks the N-terminal domain found in the full-length 150-kD protein. Immunohistochemical analysis and cell fractionation detected the 150-kD protein in both the nucleus and cytoplasm, and the 110-kD protein in the nucleus only. Agranat et al. (2008) stated that the 2 major ADAR1 isoforms are expressed from 2 distinct promoters. </p><p>By Western blot analysis of human amnion U cells, Patterson and Samuel (1995) showed that expression of the 110-kD ADAR protein was constitutive, whereas the expression of full-length 150-kD ADAR protein was induced by interferon-alpha (147660). Western blot analysis of interferon-treated U cell nuclear lysates subjected to Northwestern (RNA-protein) blot analysis or RNA-Sepharose affinity chromatography demonstrated that both ADAR isoforms bound to dsRNA, but neither bound to single-stranded RNA (ssRNA). </p><p>O'Connell et al. (1995) cloned the rat DSRAD gene and showed that the predicted protein is 79% identical to the human sequence. O'Connell et al. (1995) also found that the protein is ubiquitously expressed and showed by immunohistochemistry that it has a widespread distribution in the rat brain. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Herbert et al. (2002) reported that ADAR, which catalyzes the deamination of adenosine to inosine in dsRNA substrates, induces translation within the nucleus, possibly at the surface of the nucleolus. They found that this activity does not depend on RNA editing. The authors defined 2 regions within ADAR that act independently of each other to induce translation: the first includes the dsRNA-binding domains (DRBMs) of ADAR, while the second maps to the C-terminal portion of the catalytic domain. Point mutations within each domain were identified that reduced nuclear translation; those in the DRBM region also diminished RNA binding. This report added to the growing functionality ascribed to the nucleus. </p><p>In crosslinking and coimmunoprecipitation experiments on HeLa cell nuclear extracts, Agranat et al. (2008) showed that ADAR1 associated with the RNA surveillance protein HUPF1 (RENT1; 601430) in the supraspliceosome, a 21-megadalton nuclear ribonucleoprotein complex. The interaction did not depend on RNA. Knockdown of ADAR1 with small interfering RNA upregulated the expression of 4 of 6 genes that undergo both A-to-I editing by ADARs and degradation via HUPF1. </p><p>To determine the specifics of RNA editing by ADAR1, Liddicoat et al. (2015) generated mice with an editing-deficient knockin mutation, Adar1(E861A). Adar1(E861A/E861A) embryos died at approximately embryonic day 13.5, with activated interferon (see 147660) and double-stranded RNA (dsRNA)-sensing pathways. Genomewide analysis of the in vivo substrates of ADAR1 identified clustered hyperediting within long dsRNA stem loops within 3-prime untranslated regions of endogenous transcripts. Concurrent deletion of the cytosolic sensor of dsRNA MDA5 (606951) rescued embryonic death and other phenotypes of Adar1(E861A/E861A). Liddicoat et al. (2015) concluded that adenosine-to-inosine editing of endogenous dsRNA is the essential function of ADAR1, preventing the activation of the cytosolic dsRNA response by endogenous transcripts. </p><p>Tan et al. (2017) reported dynamic spatiotemporal patterns and novel regulators of RNA editing, discovered through an extensive profiling of adenosine-to-inosine RNA editing in 8,551 human samples (representing 53 body sites from 552 individuals) from the Genotype-Tissue Expression (GTEx) project and in hundreds of other primate and mouse samples. Tan et al. (2017) showed that editing levels in nonrepetitive coding regions vary more between tissues than editing levels in repetitive regions. Globally, ADAR1 is the primary editor of repetitive sites and ADAR2 (601218) is the primary editor of nonrepetitive coding sites, whereas the catalytically inactive ADAR3 (602065) predominantly acts as an inhibitor of editing. Cross-species analysis of RNA editing in several tissues revealed that species, rather than tissue type, is the primary determinant of editing levels, suggesting stronger cis-directed regulation of RNA editing for most sites, although the small set of conserved coding sites is under stronger trans-regulation. Tan et al. (2017) curated an extensive set of ADAR1 and ADAR2 targets and showed that many editing sites display distinct tissue-specific regulation by the ADAR enzymes in vivo. The authors also found that AIMP2 (600859), a component of the aminoacyl-tRNA synthetase complex, interacts with both ADAR1 and ADAR2 and reduces editing by enhancing their degradation. </p><p>Ishizuka et al. (2019) demonstrated that loss of function of the RNA-editing enzyme ADAR1 in tumor cells profoundly sensitizes tumors to immunotherapy and overcomes resistance to checkpoint blockade. In the absence of ADAR1, A-to-I editing of interferon-inducible RNA species is reduced, leading to double-stranded RNA ligand sensing by PKR (176871) and MDA5; this results in growth inhibition and tumor inflammation, respectively. Loss of ADAR1 overcomes resistance to PD1 (600244) checkpoint blockade caused by inactivation of antigen presentation by tumor cells. Thus, effective antitumor immunity is constrained by inhibitory checkpoints such as ADAR1 that limit the sensing of innate ligands. The induction of sufficient inflammation in tumors that are sensitized to interferon can bypass the therapeutic requirement for CD8+ T cell recognition of cancer cells and may provide a general strategy to overcome immunotherapy resistance. </p><p>By knockout analysis, Zhang et al. (2022) showed that Adar1 repressed production of Z-form double-stranded RNA elements (Z-RNAs), as deletion of Adar1 led to accumulation of endogenous Z-RNA in mouse embryo fibroblasts (MEFs) and other mouse cells. Adar1 repressed Ifn (see 147640)-stimulated Z-RNAs formed within the 3-prime UTRs of mRNAs from Ifn-stimulated genes; the repression by Adar1 was completed through direct sequestration and required its functional Z-alpha domain. Accumulation of Z-RNAs resulted from the activation of Zbp1 (606750) caused by the loss of Adar1 in the nucleus, leading to Ripk3 (605817)-mediated necroptosis in MEFs. The authors identified CBL0137 as a compound that induced Z-DNA formation in mammalian genomic DNA. Z-DNA, however, shares almost-identical structures with Z-RNA, and both Z-DNA and Z-RNA bind ZBP1. Treatment with CBL0137 activated Zbp1 and led to Z-DNA formation followed by Zbp1-dependent rupture of the nuclear envelope, resulting in nuclear necroptosis in wildtype MEFs, similar to Adar1 loss-induced Zbp1 activation and necroptosis. Analysis with tumor fibroblasts revealed that CBL0137 treatment also induced rampant Z-DNA formation and ZBP1-dependent necroptosis. Furthermore, CBL0137 reversed immune checkpoint blockade (ICB) resistance by inducing ZBP1-initiated necroptosis, thus demonstrating that ADAR1 repressed endogenous Z-RNAs by inhibiting ZBP1, and identifying ZBP1-mediated necroptosis as a new determinant of tumor immunogenicity masked by ADAR1. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Wang et al. (1995) found that the DRADA gene spans 30 kb and contains 15 exons. Transcription of the DRADA gene is initiated at multiple sites, 164 to 216 nucleotides upstream of the translation initiation codon. This nuclear-localized enzyme is involved in the RNA editing required for the expression of certain subtypes of glutamate-gated ion channel subunits. Knowledge of gene structure and sequence should facilitate study of involvement of DRADA in hereditary diseases that may be the result of malfunction of glutamate-gated ion channels. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using cloned probes on Southern blots of DNA from a panel of rodent-human somatic cell hybrids, Wathelet et al. (1988) assigned the IFI4 (ADAR) gene to chromosome 1. (At the Human Gene Mapping Workshop 10 in New Haven in 1989, a system of gene designation was initiated: G = gene; 1 = chromosome number; P = protein; 1 = consecutive gene of this category assigned to this chromosome. Thus the temporary symbol for this protein of unknown function was G1P1.) </p><p>By fluorescence in situ hybridization, Weier et al. (1995) mapped the DSRAD gene to 1q21.1-q21.2, centromeric to the marker D1S1705. Wang et al. (1995) mapped the DRADA gene to 1q21 by fluorescence in situ hybridization. By FISH, Weier et al. (2000) mapped the mouse homolog (Adar) to chromosome 3F2. </p><p>By genomic sequence analysis, Scott (2007) determined that the IFI4 gene and the ADAR gene are identical.</p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Dyschromatosis Symmetrica Hereditaria</em></strong></p><p>
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Patients with dyschromatosis symmetrica hereditaria (DSH; 127400) have pinpoint, pea-sized hyperpigmented and hypopigmented macules on the backs of their hands and the tops of their feet. The face is spared apart from a few scattered small discrete pigmented macules. These abnormalities are asymptomatic and do not affect the general health of the patient. Miyamura et al. (2003) mapped a locus for DSH to chromosome 1q21.3 where the DSRAD gene is located. In affected members of 4 families segregating DSH, Miyamura et al. (2003) identified heterozygosity for mutations in the DSRAD gene (146920.0001-146920.0004). </p><p>Miyamura et al. (2003) commented on the fact that heterozygosity for the Dsrad knockout causes embryonic lethality in mice (Wang et al., 2000), whereas patients heterozygous for the orthologous human gene have DSH, a disorder with a good prognosis. DSRAD is ubiquitously expressed in the skin; the reason the skin lesions are localized specifically on the backs of hands and on tops of the feet was unknown. Miyamura et al. (2003) speculated that when melanoblasts migrate from the neural crest to the skin during development, a greater reduction in DSRAD activity might occur at anatomic sites distant from the neural crest. Failure of correct RNA editing may induce the differentiation of melanoblasts to hyperactive or hypoactive melanocytes, then colonizing in an irregular distribution in the skin lesions. </p><p>In affected members of 6 Chinese multigeneration families and 2 sporadic patients with DSH, Zhang et al. (2004) identified 7 novel heterozygous mutations in the ADAR gene. </p><p>In a 22-year-old Japanese woman who had DSH associated with dystonia, mental deterioration, and intracranial calcifications, Tojo et al. (2006) identified heterozygosity for a missense mutation in the ADAR gene (G1007R; 146920.0011). Her unaffected mother and sister did not carry the mutation; DNA was unavailable from her affected deceased father. </p><p>In a Taiwanese woman with DSH, Chao et al. (2006) identified heterozygosity for a nonsense mutation in the ADAR gene (Q693X; 146920.0005) that segregated with disease in the family. </p><p>In affected members of a large 5-generation Chinese family with DSH, Xing et al. (2007) identified heterozygosity for 2-bp deletion (146920.0006) in the ADAR gene. </p><p>In an 11-year-old Japanese boy who had DSH associated with dystonia, mental deterioration, and intracranial calcifications, Kondo et al. (2008) identified heterozygosity for the previously reported G1007R mutation in the ADAR gene (146920.0011). His mother, who had skin lesions but no neurologic features, was also heterozygous for the mutation. </p><p>In a 12-year-old Chinese girl with DSH and her affected father and paternal grandfather, Dong et al. (2009) sequenced the ADAR gene and identified heterozygosity for an H958R substitution in all 3. The mutation was not found in the proband's unaffected paternal uncle and aunt, or in 50 unrelated Chinese controls. </p><p><strong><em>Aicardi-Goutieres Syndrome 6</em></strong></p><p>
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Rice et al. (2012) identified 9 mutations in the ADAR1 gene in 10 families with Aicardi-Goutieres syndrome (AGS6; 615010). The missense mutation pro193 to ala (P193A; 146920.0007) occurred in 5 families. Two unrelated affected individuals harbored a heterozygous de novo missense mutation, gly1007 to arg (G1007R; 146920.0011). This mutation appeared to have a dominant-negative effect. Of the 8 amino acid substitutions identified, 7 involved residues situated in the catalytic domain of ADAR1; 5 of these 7 (arg892, lys999, gly1007, tyr1112, and asp1113) lie along the surface of the protein that interacts with double-stranded RNA, and the 2 others (ala870 and ile872) lie internal to the domain structure and are predicted to destabilize the protein. In contrast, pro193 is positioned within the Z-DNA/Z-RNA-binding domain. In the wildtype protein, pro193 makes direct contact with the nucleic acid, and substitution of this residue with alanine removes important atomic interactions between the protein and DNA/RNA. </p><p>The recurrent mutation P193A (146920.0007) implicates the IFN-inducible p150 isoform of ADAR1 in the Aicardi-Goutieres syndrome phenotype. Mice lacking Adar1 die by around embryonic day 12.5 owing to defective hematopoiesis and widespread apoptosis, which are associated with global upregulation of IFN-stimulated genes, indicating that ADAR1 acts as a suppressor of type I interferon signaling. Rice et al. (2012) used whole blood from 8 ADAR1 mutation-positive individuals to perform quantitative RT-PCR to analyze the mRNA levels of 15 IFN-stimulated gene (IsgS). Compared to 9 controls, all tested individuals with mutations in ADAR1, including the 2 individuals harboring the heterozygous de novo gly1007-to-arg (G1007R; 146920.0011) mutation, showed a consistent pattern of ISG upregulation. Rice et al. (2012) analyzed the 6 most highly expressed ISGs in 10 ADAR1 mutation-positive AGS cases, 6 sets of parents with heterozygous mutations, and 18 ADAR1 mutation-positive individuals with DSH. Expression was variably higher in AGS heterozygous parents and DSH cases versus controls, whereas individuals with a clinical diagnosis of AGS (due either to biallelic mutations in ADAR1 or a heterozygous mutation resulting in the G1007R amino-acid substitution) had even higher levels of expression. </p><p>In 7 patients, including 2 sibs, with atypical AGS6, Livingston et al. (2014) identified compound heterozygous mutations in the ADAR gene (see, e.g., 146920.0007, 146920.0016). Six of the patients carried the P193A mutation on 1 allele. Two additional half-sibs with the disorder were found to carry a heterozygous G1007R missense mutation; the second mutation was likely not detected in these patients. Functional studies of the variants were not performed. These patients were ascertained from a cohort of patients with bilateral striatal necrosis who presented in infancy or early childhood with rapidly progressive severe developmental regression and incapacitating dystonia. Analysis of blood samples showed an upregulation of interferon-stimulated genes. No interferon signature was found in 4 children with a similar disorder who did not have ADAR mutations. </p><p><strong><em>Role in Innate Immunity</em></strong></p><p>
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Because of the 2 to 10% primary failure rate of measles vaccination and the importance of innate immunity to prevent or reduce viral replication and spread until the adaptive immune response to eliminate the virus, Haralambieva et al. (2011) performed a comprehensive candidate gene association study in a racially diverse cohort of 745 healthy schoolchildren in Minnesota who had had 2 doses of measles vaccine. Variants within DDX58 (609631) were associated with measles-specific antibody variations in Caucasians. Four DDX58 polymorphisms in high linkage disequilibrium were also associated with variations in measles-specific IFNG (147570) and IL2 (147680) secretion in Caucasians. ADAR variants also had a role in regulating measles-specific IFNG responses in Caucasians. Two intronic OAS1 (164350) SNPs were associated with increased neutralizing antibody levels in African Americans. Haralambieva et al. (2011) concluded that multiple innate immunity genes and genetic variants are likely involved in modulating the adaptive immune response to live attenuated measles vaccine in Caucasians and African Americans. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Wang et al. (2000) knocked out the Adar1 gene in mice by targeted disruption and found that heterozygosity for the Adar1 knockout causes embryonic lethality. To understand the mechanism of embryonic lethality, they studied staged chimeric mouse embryos with a high contribution from embryonic stem cells with a functional null allele for Adar1. No live chimeric embryo with a high degree of contribution by Adar1 +/- cells was recovered beyond embryonic day (E) 14.5. The primary defects were in the hematopoietic system, with a large number of nucleated erythrocytes in chimeric mice. Adar1 expression normally increases at E13 to E14 in the liver. Based on these results, Wang et al. (2000) concluded that a regulated increase in Adra1 expression in liver is required at E12 and E13. Failure to increase Adar1 may result in underediting of the RNA of currently unknown target genes, which in turn affects proliferation and/or differentiation of erythrocytes. Thus, regulated levels of ADAR expression appear to be critical for embryonic erythropoiesis in the liver. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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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>16 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 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</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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ADAR, ARG474TER
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<br />
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SNP: rs121912421,
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gnomAD: rs121912421,
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ClinVar: RCV000015940, RCV003764577
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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 Japanese family with autosomal dominant dyschromatosis symmetrica hereditaria (DSH; 127400) in members of 4 successive generations, Miyamura et al. (2003) identified a CGA-to-TGA transition in exon 2 of the DSRAD gene, resulting in a nonsense change, arg474 to stop (R474X). </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 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</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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ADAR, LEU923PRO
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<br />
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SNP: rs28936680,
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ClinVar: RCV000015941
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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 Japanese family with dyschromatosis symmetrica hereditaria (DSH; 127400) in members of 4 successive generations, Miyamura et al. (2003) demonstrated that affected members were heterozygous for a CTC-to-CCC transition in exon 10 of the DSRAD gene, resulting in a leu923-to-pro (L923P) amino acid change. </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 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</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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ADAR, LYS952TER
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<br />
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SNP: rs121912422,
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ClinVar: RCV000015942
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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 Japanese family with autosomal dominant dyschromatosis symmetrica hereditaria (DSH; 127400) in 4 generations, Miyamura et al. (2003) demonstrated an AAA-to-TAA transversion in exon 10 of the DSRAD gene, resulting in a lys952-to-stop (K952X) mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</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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ADAR, PHE1165SER
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<br />
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SNP: rs28936681,
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gnomAD: rs28936681,
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ClinVar: RCV000015943
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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 Japanese family with autosomal dominant dyschromatosis symmetrica hereditaria (DSH; 127400) in 5 successive generations, Miyamura et al. (2003) identified a TTT-to-TCT transition in exon 15 of the DSRAD gene, resulting in a phe1165-to-ser (F1165S) mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</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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ADAR, GLN693TER
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<br />
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SNP: rs121912423,
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gnomAD: rs121912423,
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ClinVar: RCV000015944
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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 Taiwanese woman with dyschromatosis symmetrica hereditaria (DSH; 127400), Chao et al. (2006) identified a 2077C-T transition in exon 5 of the ADAR gene, resulting in a gln693-to-ter (Q693X) substitution. The mutation was also found in her affected sister and daughter but not in unaffected members of the family. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0006 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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ADAR, 2-BP DEL, 941CT
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<br />
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SNP: rs387906541,
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ClinVar: RCV000015945
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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 affected members of a large 5-generation Chinese family with dyschromatosis symmetrica hereditaria (DSH; 127400), Xing et al. (2007) identified a 2-bp deletion (941delCT) in exon 2 of the ADAR gene, resulting in a frameshift and premature termination of the protein. The family was from Hunan province. </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 AICARDI-GOUTIERES SYNDROME 6</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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ADAR, PRO193ALA
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<br />
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SNP: rs145588689,
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gnomAD: rs145588689,
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ClinVar: RCV000114336, RCV000255775, RCV000288094, RCV000352411, RCV000548694, RCV000624331, RCV000778185
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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 5 families of European descent with Aicardi-Goutieres syndrome (AGS6; 615010), Rice et al. (2012) identified a heterozygous C-to-G transversion at nucleotide 577 in exon 2 of the ADAR gene, resulting in a pro-to-ala substitution at codon 193 (P193A). In 2 of these families, one Norwegian and the other Spanish, the mutation occurred in compound heterozygosity with an arg892-to-his mutation (146920.0008). The other 3 families respectively carried the P193A mutation in compound heterozygosity with A870T (146920.0009), I872T (146920.0014), and a 5-bp deletion (146920.0015). Proline-293 is highly evolutionarily conserved and positioned within the Z-DNA/Z-RNA-binding domain. This variant was also observed in 41 subjects (32 of 4,350 European Americans and 9 of 2,203 African Americans) in the Exome Variant Server database. </p><p>In 6 patients, including 2 sibs, with atypical AGS6, Livingston et al. (2014) identified the P193A mutation in compound heterozygosity with another pathogenic ARAR mutation (see, e.g., I872T and R544XC, 146920.0016). </p>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>.0008 AICARDI-GOUTIERES SYNDROME 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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|
ADAR, ARG892HIS
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|
<br />
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|
SNP: rs398122892,
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|
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|
|
|
gnomAD: rs398122892,
|
|
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|
|
|
ClinVar: RCV000032650, RCV003764649
|
|
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|
|
</span>
|
|
</div>
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<div>
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|
<span class="mim-text-font">
|
|
<p>In patients from a Norwegian and a Spanish family, respectively, with Aicardi-Goutieres syndrome-6 (AGS6; 615010), Rice et al. (2012) identified compound heterozygosity for mutations in the ADAR gene, a P193A mutation (146920.0007) and a G-to-A transition at nucleotide 2675 in exon 9, resulting in an arg-to-his substitution at codon 892 (R892H). The patients from the Spanish family were identical twins. The R892H mutation was not observed in over 12,000 control alleles in the Exome Variant Server database. An arginine at position 892 in this gene is evolutionarily invariant to C. elegans. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 AICARDI-GOUTIERES SYNDROME 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
ADAR, ALA870THR
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|
|
<br />
|
|
|
|
SNP: rs398122893,
|
|
|
|
|
|
|
|
ClinVar: RCV000032651
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; 615010) from an Italian family, Rice et al. (2012) found compound heterozygosity for the P193A mutation (146920.0007) in ADAR and a G-to-A transition at nucleotide 2608 in exon 8, resulting in an ala-to-thr substitution at codon 870 (A870T). This mutation was not identified among the 12,000 control alleles within the Exome Variant Server database. An alanine at position 870 in this gene is evolutionarily invariant through C. elegans. </p>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>.0010 AICARDI-GOUTIERES SYNDROME 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
ADAR, ASP1113HIS
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|
|
<br />
|
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|
|
SNP: rs398122894,
|
|
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|
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|
|
ClinVar: RCV000032652
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; 615010) from a consanguineous Pakistani family, Rice et al. (2012) identified homozygosity for a G-to-C transversion at nucleotide 3337 in exon 14 of the ADAR gene, resulting in an asp-to-his substitution at codon 1113 (D1113H). Both parents were heterozygous and this mutation was not identified in the Exome Variant Server database. An aspartic acid at position 1113 in this gene is evolutionarily invariant through C. elegans. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 DYSCHROMATOSIS SYMMETRICA HEREDITARIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
AICARDI-GOUTIERES SYNDROME 6, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADAR, GLY1007ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398122822,
|
|
|
|
|
|
|
|
ClinVar: RCV000032653, RCV000032654, RCV000762850, RCV001091722
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Dyschromatosis Symmetrica Hereditaria</em></strong></p><p>
|
|
In a 22-year-old Japanese woman with dyschromatosis symmetrica hereditaria (DSH; 127400) associated with dystonia, mental deterioration, and tissue calcification, Tojo et al. (2006) identified heterozygosity for a c.3019G-A transition in exon 11 of the ADAR gene, resulting in a gly1007-to-arg (G1007R) substitution. Her unaffected mother and sister did not carry the mutation; DNA was unavailable from her affected deceased father. </p><p>In an 11-year-old Japanese boy with DSH and dystonia, mental deterioration, and brain calcification, Kondo et al. (2008) identified heterozygosity for the previously reported G1007R substitution in the ADAR gene. His mother, who had skin lesions but no neurologic features, was also heterozygous for the mutation. </p><p><strong><em>Aicardi-Goutieres Syndrome</em></strong></p><p>
|
|
In 2 individuals, 1 of Brazilian origin and 1 of European American origin, with Aicardi-Goutieres syndrome-6 (AGS6; 615010), Rice et al. (2012) identified a heterozygous de novo mutation in exon 11 of the ADAR gene: a G-to-A transition at nucleotide 3019, resulting in a gly-to-arg substitution at codon 1007 (G1007R). Using an ADAR1 editing substrate, miR376-a2 (610960), Rice et al. (2012) found that, of 6 ADAR mutations tested, only the G1007R variant showed a significant effect on editing, with levels of editing equivalent to those seen with inactive protein. The proximity of G1007R to the RNA backbone and the possibility for an arginine residue to make polymorphic interactions there suggested a mechanism whereby arg1007 might confer a dominant-negative effect: by binding more tightly to RNA the mutant protein could act as a competitive inhibitor of wildtype protein while being itself catalytically inactive. Rice et al. (2012) found that a plasmid expressing G1007R ADAR1 showed stronger inhibition of wildtype ADAR1 than equivalent amounts of a plasmid expressing catalytically inactive ADAR1. </p><p>In 2 half-sibs with AGS6, Livingston et al. (2014) found the G1007R mutation in heterozygosity. </p><p>In a 5-year-old boy, born of unrelated Hispanic parents, with onset of nonsyndromic spastic paraplegia at age 2 years following normal psychomotor development, Crow et al. (2014) identified a de novo heterozygous G1007R mutation in the ADAR1 gene. The mutation was found by exome sequencing and confirmed by Sanger sequencing. Brain imaging and cognition were normal, and laboratory studies showed increased interferon. Crow et al. (2014) emphasized the emerging phenotypic variability associated with AGS, noting that neurologic dysfunction is not always marked in this disorder. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 AICARDI-GOUTIERES SYNDROME 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADAR, TYR1112PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398122895,
|
|
|
|
|
|
|
|
ClinVar: RCV000032655
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; 615010) from a consanguineous Pakistani family, Rice et al. (2012) identified homozygosity for an A-to-T transversion at nucleotide 3335 in exon 14 of the ADAR gene, resulting in a tyr-to-phe substitution at codon 1112 (Y1112F). This mutation was not identified among 12,000 control alleles in the Exome Variant Server database. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 AICARDI-GOUTIERES SYNDROME 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADAR, LYS999ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398122896,
|
|
|
|
|
|
|
|
ClinVar: RCV000032656
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; 615010) from a nonconsanguineous Indian family, Rice et al. (2012) identified a homozygous G-to-T transversion at nucleotide 2997 in exon 11 of the ADAR gene, resulting in a lys-to-asn substitution at codon 999 (K999N). Both parents were carriers of the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 AICARDI-GOUTIERES SYNDROME 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADAR, ILE872THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398122897,
|
|
|
|
|
|
gnomAD: rs398122897,
|
|
|
|
|
|
ClinVar: RCV000032657
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient of Caucasian British origin with Aicardi-Goutieres syndrome-6 (AGS6; 615010), Rice et al. (2012) identified compound heterozygosity for the pro193-to-ala (P193A; 146920.0007) mutation in the ADAR gene and a T-to-C transition at nucleotide 2615 in exon 8, resulting in an ile-to-thr substitution at codon 872 (I872T; 146920.0014). This mutation involving an evolutionarily conserved residue was not identified in 12,000 control samples. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 AICARDI-GOUTIERES SYNDROME 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADAR, 5-BP DEL, NT1076
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398122898,
|
|
|
|
|
|
|
|
ClinVar: RCV000032658
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Aicardi-Goutieres syndrome-6 (AGS6; 615010) from an Italian family, Rice et al. (2012) identified a heterozygous 5-bp deletion in the ADAR gene (1076_1080del) that resulted in frameshift and premature termination (Lys359ArgfsTer14). The patient was compound heterozygous for the P193A mutation (see 146920.0007). The frameshift mutation was not identified among 12,000 control alleles in the Exome Variant Server database. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 AICARDI-GOUTIERES SYNDROME 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ADAR, ARG544TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs768943773,
|
|
|
|
|
|
gnomAD: rs768943773,
|
|
|
|
|
|
ClinVar: RCV000114429
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Caucasian sibs with atypical Aicardi-Goutieres syndrome-6 (AGS6; 615010), Livingston et al. (2014) identified compound heterozygosity for 2 mutations in the ADAR gene: a c.1630C-T transition in exon 3, resulting in an arg544-to-ter (R544X) substitution, and P193A (146920.0007). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Agranat, L., Raitskin, O., Sperling, J., Sperling, R.
|
|
<strong>The editing enzyme ADAR1 and the mRNA surveillance protein hUpf1 interact in the cell nucleus.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 5028-5033, 2008.
|
|
|
|
|
|
[PubMed: 18362360]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0710576105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bass, B. L., Weintraub, H.
|
|
<strong>An unwinding activity that covalently modifies its double-stranded RNA substrate.</strong>
|
|
Cell 55: 1089-1098, 1988.
|
|
|
|
|
|
[PubMed: 3203381]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(88)90253-x]
|
|
|
|
|
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</p>
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OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
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