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Entry
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- #615010 - AICARDI-GOUTIERES SYNDROME 6; AGS6
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- OMIM
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<p>
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<span class="h4">#615010</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/615010"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS225750"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</h4>
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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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</a>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div><a href="https://clinicaltrials.gov/search?cond=AICARDI-GOUTIERES SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=1309&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1475/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=615010[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><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=51" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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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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</a>
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</span>
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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/disease/DOID:0050629" 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="http://www.informatics.jax.org/disease/615010" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0050629" 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': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></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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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 51<br />
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<strong>DO:</strong> 0050629<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="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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615010
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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AICARDI-GOUTIERES SYNDROME 6; AGS6
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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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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/1/1194?start=-3&limit=10&highlight=1194">
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1q21.3
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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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">
|
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<a href="/entry/615010"> 615010 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</td>
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<td>
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<span class="mim-font">
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ADAR
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/146920"> 146920 </a>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/615010" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS225750" class="btn btn-info" role="button"> Phenotypic Series </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/615010" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/615010" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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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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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
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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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<span class="h5 mim-font">
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<strong> HEAD & NECK </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Head </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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|
|
- Microcephaly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
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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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<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
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</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nystagmus (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br />
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</span>
|
|
</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>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Delayed development, severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837330&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837330</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
|
|
Developmental regression (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/609225004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">609225004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836830&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836830</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002376" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002376</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002376" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002376</a>]</span><br /> -
|
|
Tremor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26079004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26079004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R25.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R25.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span><br /> -
|
|
Stiffness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271587009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271587009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427008&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427008</a>]</span><br /> -
|
|
Rigidity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16046003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16046003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700109&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700109</a>, <a href="https://bioportal.bioontology.org/search?q=C0026837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002063" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002063</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002063" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002063</a>]</span><br /> -
|
|
Dystonia, severe (in all limbs) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4013992&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4013992</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
|
|
Loss of speech <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0542223&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0542223</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002371</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002371</a>]</span><br /> -
|
|
Loss of ability to walk <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836843&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836843</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002505</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002505</a>]</span><br /> -
|
|
Bilateral striatal necrosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4013993&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4013993</a>]</span><br /> -
|
|
Signal changes in the caudate and putamen <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4013994&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4013994</a>]</span><br /> -
|
|
Intracranial calcifications (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5886739&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5886739</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0430048" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0430048</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0430048" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0430048</a>]</span><br /> -
|
|
Leukodystrophy (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/192781003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">192781003</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/330.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">330.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023520&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023520</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002415" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002415</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002415" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002415</a>]</span><br />
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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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<span class="h5 mim-font">
|
|
<strong> HEMATOLOGY </strong>
|
|
</span>
|
|
</div>
|
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<div style="margin-left: 2em;">
|
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<div>
|
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<span class="mim-font">
|
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|
|
- Hemolytic anemia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61261009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61261009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D55-D59" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D55-D59</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002878&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002878</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001878</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001878</a>]</span><br />
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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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<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
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|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Upregulation of alpha-interferon-stimulated genes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4013996&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4013996</a>]</span><br />
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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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<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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|
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<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset in infancy or early childhood<br /> -
|
|
Onset of symptoms often associated with nonspecific febrile illness<br /> -
|
|
Rapidly progressive deterioration (in some patients)<br />
|
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|
|
</span>
|
|
</div>
|
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</div>
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
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|
|
- Caused by mutation in the RNA-specific adenosine deaminase gene (ADAR, <a href="/entry/146920#0007">146920.0007</a>)<br />
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|
|
</span>
|
|
</div>
|
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|
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</div>
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</div>
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|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
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|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
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|
|
|
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|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Aicardi-Goutieres syndrome
|
|
- <a href="/phenotypicSeries/PS225750">PS225750</a>
|
|
- 9 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<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">
|
|
<a href="/entry/615010"> Aicardi-Goutieres syndrome 6 </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615010"> 615010 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/146920"> ADAR </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/146920"> 146920 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/727?start=-3&limit=10&highlight=727"> 2q24.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615846"> Aicardi-Goutieres syndrome 7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615846"> 615846 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606951"> IFIH1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606951"> 606951 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/281?start=-3&limit=10&highlight=281"> 3p21.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/225750"> Aicardi-Goutieres syndrome 1, dominant and recessive </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/225750"> 225750 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606609"> TREX1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606609"> 606609 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/5/716?start=-3&limit=10&highlight=716"> 5q33.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619486"> ?Aicardi-Goutieres syndrome 8 </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619486"> 619486 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617910"> LSM11 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617910"> 617910 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/605?start=-3&limit=10&highlight=605"> 11q13.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610329"> Aicardi-Goutieres syndrome 3 </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610329"> 610329 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610330"> RNASEH2C </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610330"> 610330 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/12/81?start=-3&limit=10&highlight=81"> 12p13.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619487"> Aicardi-Goutieres syndrome 9 </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619487"> 619487 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617876"> RNU7-1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617876"> 617876 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/13/185?start=-3&limit=10&highlight=185"> 13q14.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610181"> Aicardi-Goutieres syndrome 2 </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610181"> 610181 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610326"> RNASEH2B </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610326"> 610326 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/337?start=-3&limit=10&highlight=337"> 19p13.13 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610333"> Aicardi-Goutieres syndrome 4 </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610333"> 610333 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606034"> RNASEH2A </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606034"> 606034 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/20/264?start=-3&limit=10&highlight=264"> 20q11.23 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612952"> Aicardi-Goutieres syndrome 5 </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>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612952"> 612952 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606754"> SAMHD1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606754"> 606754 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
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<p>A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-6 (AGS6) is caused by homozygous or compound heterozygous mutation in the ADAR gene (<a href="/entry/146920">146920</a>) on chromosome 1q21.</p><p>Dyschromatosis symmetrica hereditaria (<a href="/entry/127400">127400</a>) is an allelic disorder, and patients have been reported who exhibit features of both disorders.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (<a href="/entry/225750">225750</a>).</p>
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<p><a href="#3" 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> reported 10 families with 14 children, including 1 set of identical twins, with Aicardi-Goutieres syndrome. The families were of diverse ethnic backgrounds including Norwegian, Italian, Pakistani, Brazilian, Indian, British, Spanish, mixed Italian/Cuban, and European American. Two of the families were consanguineous. Clinical details included intracranial calcification and severe developmental delay in all, leukodystrophy in most, and markedly elevated cerebrospinal fluid (CSF) interferon-alpha (see <a href="/entry/147660">147660</a>) in all in whom it was measured. <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><strong><em>Clinical Variability</em></strong></p><p>
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<a href="#2" 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> reported 9 patients, including 2 sibs and 2 half-sibs, with refractory dystonia starting between ages 9 months and 5 years. Eight of the patients showed normal psychomotor development before symptom onset; the ninth patient had mild-to-moderate global developmental delay apparent in early infancy. Six of the 9 children presented between 9 and 18 months with acute onset of severe generalized dystonia in the context of a nonspecific febrile illness, such as ear infection, respiratory illness, or viral illness with rash. Clinical features included limb tremor and stiffening, rigidity, loss of previous motor and other developmental skills, and severe dystonia affecting all 4 limbs. These neurologic abnormalities developed and progressed rapidly within several weeks, and were refractory to pharmacologic management. Two additional patients had a slower course, with progressive dystonia and neurologic deterioration over several months. Three patients were retrospectively noted to have cutaneous pigmentation with freckling of the face and hands; only 1 child had vasculitic skin lesions. Brain MRI from 7 patients showed bilateral striatal necrosis, with signal changes in the caudate and putamen, often associated with swelling and later shrinkage. Three patients had evidence of intracranial calcifications, and 1 had findings suggestive of calcification. All 7 patients analyzed had blood evidence of upregulation of interferon-stimulated genes, the so-called interferon signature, even years after symptom onset. <a href="#2" 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> suggested that the interferon signature may be a reliable screening test for this disorder. <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><a href="#1" 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> reported a 5-year-old boy, born of unrelated Hispanic parents, who presented at age 2 years with toe walking and frequent falls associated with slowly progressive spastic paraplegia following normal early psychomotor development. Physical examination showed lower limb spasticity with increased tone, ankle clonus, unilateral extensor plantar response, and spastic diplegic gait. Brain imaging and cognition were normal. Exome sequencing identified a de novo heterozygous mutation in the ADAR1 gene (G1007R; <a href="/entry/146920#0011">146920.0011</a>) that had been identified in patients with classic AGS6. Laboratory studies revealed evidence of increased interferon. <a href="#1" 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 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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<p>The transmission pattern of AGS6 in the families reported by <a href="#3" 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> was consistent with autosomal recessive inheritance. <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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<p>By whole-exome sequencing in 4 probands with a diagnosis of Aicardi-Goutieres syndrome in whom mutations in known causative genes had been excluded, <a href="#3" 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 heterozygous or homozygous mutations in the ADAR1 gene. They sequenced other individuals without known mutations from their AGS cohort and identified a total of 9 distinct mutations, including 1 recurrent missense mutation, pro193 to ala (P193A; <a href="/entry/146920#0007">146920.0007</a>). Two unrelated affected individuals harbored a heterozygous de novo missense mutation, gly1007 to arg (G1007R; <a href="/entry/146920#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><a href="#3" 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> noted that the G1007R mutation in ADAR1 had previously been reported (see <a href="/entry/146920#0011">146920.0011</a>) in 2 individuals with dyschromatosis symmetrica hereditaria (DSH; <a href="/entry/127400">127400</a>) who also demonstrated neurodegeneration with dystonia and intracranial calcification. The skin lesions typical of DSH had not been reported in AGS (they are distinct from AGS-related chilblains) and no individual with AGS6 had obvious features of DSH. Of note, DSH has only rarely been reported outside of Japan and China. Moreover, marked variability in expression of DSH is well recognized even within families. <a href="#3" 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> remarked that although their findings did not necessarily implicate dysregulation of type 1 interferon in the DSH phenotype, they suggested that missense and null heterozygous mutations in ADAR1 are consistent with both DSH and with carrier or affected status for AGS. Thus, <a href="#3" 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> suggested that the lack of DSH skin features in their AGS cases and their heterozygous parents most likely relates to nonpenetrance and/or variable expressivity due to ancestry or other genetic or nongenetic factors. <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 presenting as bilateral striatal necrosis with severe dystonia, <a href="#2" 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="/entry/146920#0007">146920.0007</a>; <a href="/entry/146920#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. 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>
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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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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.
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<strong>A type I interferon signature identifies bilateral striatal necrosis due to mutations in ADAR1.</strong>
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J. Med. Genet. 51: 76-82, 2014.
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[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://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'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmedgenet-2013-102038" target="_blank">Full Text</a>]
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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.
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<strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong>
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Nature Genet. 44: 1243-1248, 2012.
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[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://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'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.2414" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 06/13/2024
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Cassandra L. Kniffin - updated : 12/15/2014<br>Cassandra L. Kniffin - updated : 4/9/2014
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Ada Hamosh : 1/9/2013
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carol : 06/13/2024
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carol : 04/29/2017<br>carol : 04/28/2017<br>alopez : 12/18/2014<br>mcolton : 12/16/2014<br>mcolton : 12/16/2014<br>ckniffin : 12/15/2014<br>alopez : 4/14/2014<br>ckniffin : 4/9/2014<br>joanna : 3/21/2014<br>alopez : 1/10/2013<br>alopez : 1/10/2013
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AICARDI-GOUTIERES SYNDROME 6; AGS6
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<strong>ORPHA:</strong> 51;
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<strong>DO:</strong> 0050629;
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1q21.3
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Aicardi-Goutieres syndrome 6
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615010
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Autosomal recessive
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ADAR
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146920
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<p>A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-6 (AGS6) is caused by homozygous or compound heterozygous mutation in the ADAR gene (146920) on chromosome 1q21.</p><p>Dyschromatosis symmetrica hereditaria (127400) is an allelic disorder, and patients have been reported who exhibit features of both disorders.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750).</p>
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<p>Rice et al. (2012) reported 10 families with 14 children, including 1 set of identical twins, with Aicardi-Goutieres syndrome. The families were of diverse ethnic backgrounds including Norwegian, Italian, Pakistani, Brazilian, Indian, British, Spanish, mixed Italian/Cuban, and European American. Two of the families were consanguineous. Clinical details included intracranial calcification and severe developmental delay in all, leukodystrophy in most, and markedly elevated cerebrospinal fluid (CSF) interferon-alpha (see 147660) in all in whom it was measured. </p><p><strong><em>Clinical Variability</em></strong></p><p>
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Livingston et al. (2014) reported 9 patients, including 2 sibs and 2 half-sibs, with refractory dystonia starting between ages 9 months and 5 years. Eight of the patients showed normal psychomotor development before symptom onset; the ninth patient had mild-to-moderate global developmental delay apparent in early infancy. Six of the 9 children presented between 9 and 18 months with acute onset of severe generalized dystonia in the context of a nonspecific febrile illness, such as ear infection, respiratory illness, or viral illness with rash. Clinical features included limb tremor and stiffening, rigidity, loss of previous motor and other developmental skills, and severe dystonia affecting all 4 limbs. These neurologic abnormalities developed and progressed rapidly within several weeks, and were refractory to pharmacologic management. Two additional patients had a slower course, with progressive dystonia and neurologic deterioration over several months. Three patients were retrospectively noted to have cutaneous pigmentation with freckling of the face and hands; only 1 child had vasculitic skin lesions. Brain MRI from 7 patients showed bilateral striatal necrosis, with signal changes in the caudate and putamen, often associated with swelling and later shrinkage. Three patients had evidence of intracranial calcifications, and 1 had findings suggestive of calcification. All 7 patients analyzed had blood evidence of upregulation of interferon-stimulated genes, the so-called interferon signature, even years after symptom onset. Livingston et al. (2014) suggested that the interferon signature may be a reliable screening test for this disorder. </p><p>Crow et al. (2014) reported a 5-year-old boy, born of unrelated Hispanic parents, who presented at age 2 years with toe walking and frequent falls associated with slowly progressive spastic paraplegia following normal early psychomotor development. Physical examination showed lower limb spasticity with increased tone, ankle clonus, unilateral extensor plantar response, and spastic diplegic gait. Brain imaging and cognition were normal. Exome sequencing identified a de novo heterozygous mutation in the ADAR1 gene (G1007R; 146920.0011) that had been identified in patients with classic AGS6. Laboratory studies revealed evidence of increased interferon. Crow et al. (2014) emphasized the phenotypic variability associated with AGS, noting that neurologic dysfunction is not always marked in this disorder. </p>
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<p>The transmission pattern of AGS6 in the families reported by Rice et al. (2012) was consistent with autosomal recessive inheritance. </p>
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<strong>Molecular Genetics</strong>
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<p>By whole-exome sequencing in 4 probands with a diagnosis of Aicardi-Goutieres syndrome in whom mutations in known causative genes had been excluded, Rice et al. (2012) identified compound heterozygous or homozygous mutations in the ADAR1 gene. They sequenced other individuals without known mutations from their AGS cohort and identified a total of 9 distinct mutations, including 1 recurrent missense mutation, pro193 to ala (P193A; 146920.0007). 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>Rice et al. (2012) noted that the G1007R mutation in ADAR1 had previously been reported (see 146920.0011) in 2 individuals with dyschromatosis symmetrica hereditaria (DSH; 127400) who also demonstrated neurodegeneration with dystonia and intracranial calcification. The skin lesions typical of DSH had not been reported in AGS (they are distinct from AGS-related chilblains) and no individual with AGS6 had obvious features of DSH. Of note, DSH has only rarely been reported outside of Japan and China. Moreover, marked variability in expression of DSH is well recognized even within families. Rice et al. (2012) remarked that although their findings did not necessarily implicate dysregulation of type 1 interferon in the DSH phenotype, they suggested that missense and null heterozygous mutations in ADAR1 are consistent with both DSH and with carrier or affected status for AGS. Thus, Rice et al. (2012) suggested that the lack of DSH skin features in their AGS cases and their heterozygous parents most likely relates to nonpenetrance and/or variable expressivity due to ancestry or other genetic or nongenetic factors. </p><p>In 7 patients, including 2 sibs, with atypical AGS6 presenting as bilateral striatal necrosis with severe dystonia, 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. No interferon signature was found in 4 children with a similar disorder who did not have ADAR mutations. </p>
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<strong>REFERENCES</strong>
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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: 25243380]
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[Full Text: https://doi.org/10.1055/s-0034-1389161]
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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.
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<strong>A type I interferon signature identifies bilateral striatal necrosis due to mutations in ADAR1.</strong>
|
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J. Med. Genet. 51: 76-82, 2014.
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[PubMed: 24262145]
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[Full Text: https://doi.org/10.1136/jmedgenet-2013-102038]
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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.
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<strong>Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature.</strong>
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Nature Genet. 44: 1243-1248, 2012.
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[PubMed: 23001123]
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[Full Text: https://doi.org/10.1038/ng.2414]
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Marla J. F. O'Neill - updated : 06/13/2024<br>Cassandra L. Kniffin - updated : 12/15/2014<br>Cassandra L. Kniffin - updated : 4/9/2014
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