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Entry
- #615846 - AICARDI-GOUTIERES SYNDROME 7; AGS7
- OMIM
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<span class="h4">#615846</span>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/615846"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS225750"> <strong>Phenotypic Series</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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<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 style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=1309&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Aicardi-Goutières syndrome&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=32207&Typ=Pat" title="IFH1-related hereditary spastic paraplegia" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">IFH1-related hereditary sp…&nbsp;</a></div>
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
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</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<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>
<div><a href="http://www.informatics.jax.org/disease/615846" 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>
<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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</div>
</div>
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<span>
<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.">
&nbsp;
</span>
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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">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>ORPHA:</strong> 51, 689231<br />
<strong>DO:</strong> 0050629<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
615846
</span>
</span>
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<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
AICARDI-GOUTIERES SYNDROME 7; AGS7
</span>
</h3>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<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">
Aicardi-Goutieres syndrome 7
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615846"> 615846 </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">
IFIH1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606951"> 606951 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/615846" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<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')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
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&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS225750" class="btn btn-info" role="button"> Phenotypic Series </a>
<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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&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
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<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/615846" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/615846" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Intrauterine growth retardation (IUGR) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22033007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22033007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/764.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">764.90</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/764.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">764.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015934&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015934</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001511" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001511</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001511" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001511</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- 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="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Abnormal ocular movements (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103252009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103252009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0497202&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0497202</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000496" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000496</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000496" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000496</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hepatomegaly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spleen </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Splenomegaly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16294009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16294009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038002</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Poor feeding <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299698007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299698007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0576456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576456</a>, <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Nephrotic syndrome (1 patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52254009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52254009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/581" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">581</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027726&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027726</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000100" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000100</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000100" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000100</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Vasculitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/31996006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">31996006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042384&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042384</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002633" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002633</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002633" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002633</a>]</span><br /> -
Atopic dermatitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/200775004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">200775004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43116000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43116000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/24079001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">24079001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L20.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L20.81</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L30.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L30.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L20.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L20.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011615</a>, <a href="https://bioportal.bioontology.org/search?q=C0013595&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013595</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001047" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001047</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000964" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000964</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001047" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001047</a>]</span><br /> -
Lack of chilblain lesions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4014467&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4014467</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Delayed psychomotor development <span class="mim-feature-ids hidden">[SNOMEDCT: <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">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a> 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> <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 /> -
Irritability, neonatal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278841&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278841</a>]</span><br /> -
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Lack of speech <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854882&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854882</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001344</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001344</a>]</span><br /> -
Psychomotor regression (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855019&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855019</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 /> -
Axial hypotonia, severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550481&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550481</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span><br /> -
Spastic quadriparesis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298282001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298282001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0575059&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0575059</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001285" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001285</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001285" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001285</a>]</span><br /> -
Dystonia <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">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> 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> <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 /> -
Seizures (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Basal ganglia calcification <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16818591000119108" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16818591000119108</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G23.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G23.8</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1389280&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1389280</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002135" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002135</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002135" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002135</a>]</span><br /> -
Cerebral atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span><br /> -
T2-weighted signal abnormalities in the deep white matter <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4014459&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4014459</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Thrombocytopenia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415116008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415116008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302215000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302215000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D69.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D69.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/287.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">287.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392386</a>, <a href="https://bioportal.bioontology.org/search?q=C0040034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040034</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> IMMUNOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Lupus-like syndrome (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/201436003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">201436003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80258006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80258006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M32.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M32.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0263591&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0263591</a>, <a href="https://bioportal.bioontology.org/search?q=C0919715&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0919715</a>]</span><br /> -
Hyperinflammatory state <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4014463&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4014463</a>]</span><br /> -
Increased alpha-interferon activity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4014464&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4014464</a>]</span><br /> -
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 /> -
Autoantibodies (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/314067002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">314067002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30621004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30621004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004358&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004358</a>, <a href="https://bioportal.bioontology.org/search?q=C1272321&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1272321</a>]</span><br /> -
Hypergammaglobulinemia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/127388009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">127388009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020455&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020455</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010702" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010702</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010702" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010702</a>]</span><br /> -
Hypocomplementemia (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0853888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853888</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset in infancy or early childhood<br /> -
Variable severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861403&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861403</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span><br /> -
Incomplete penetrance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836598&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836598</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the interferon-induced helicase C domain-containing protein 1 gene (IFIH1, <a href="/entry/606951#0001">606951.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<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>
</tbody>
</table>
</div>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
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<br />
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>TEXT</strong>
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<span class="mim-text-font">
<p>A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-7 (AGS7) is caused by heterozygous gain-of-function mutation in the IFIH1 gene (<a href="/entry/606951">606951</a>) on chromosome 2q24.</p>
</span>
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<br />
</div>
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<a id="description" class="mim-anchor"></a>
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<strong>Description</strong>
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<p>Aicardi-Goutieres syndrome-7 (AGS7) is an autosomal dominant inflammatory disorder characterized by severe neurologic impairment. Most patients present in infancy with delayed psychomotor development, axial hypotonia, spasticity, and brain imaging changes, including basal ganglia calcification, cerebral atrophy, and deep white matter abnormalities. Laboratory evaluation shows increased alpha-interferon (IFNA1; <a href="/entry/147660">147660</a>) activity with upregulation of interferon signaling and interferon-stimulated gene expression. Some patients may have normal early development followed by episodic neurologic regression (summary by <a href="#6" class="mim-tip-reference" title="Rice, G. I., del Toro Duany, Y., Jenkinson, E. M., Forte, G. M. A., Anderson, B. H., Ariaudo, G., Bader-Meunier, B., Baildam, E. M., Battini, R., Beresford, M. W., Casarano, M., Chouchane, M., and 41 others. &lt;strong&gt;Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.&lt;/strong&gt; Nature Genet. 46: 503-509, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24686847/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24686847&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24686847[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.2933&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24686847">Rice et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24686847" 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>For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (<a href="/entry/225750">225750</a>).</p>
</span>
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<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
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<p><a href="#6" class="mim-tip-reference" title="Rice, G. I., del Toro Duany, Y., Jenkinson, E. M., Forte, G. M. A., Anderson, B. H., Ariaudo, G., Bader-Meunier, B., Baildam, E. M., Battini, R., Beresford, M. W., Casarano, M., Chouchane, M., and 41 others. &lt;strong&gt;Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.&lt;/strong&gt; Nature Genet. 46: 503-509, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24686847/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24686847&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24686847[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.2933&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24686847">Rice et al. (2014)</a> reported 8 children with a neurodevelopmental disorder associated with inflammatory markers. Five patients presented with classic clinical features of AGS, including neonatal or infantile onset of growth retardation, irritability, poor feeding, axial hypotonia, and delayed psychomotor development. The most severely affected patients had microcephaly, spastic-dystonic tetraparesis, and lack of speech. Brain imaging showed cerebral atrophy with basal ganglia calcifications and abnormal T2-weighted signal abnormalities in the deep white matter. One patient had a lupus (SLE; <a href="/entry/152700">152700</a>)-like disease with vasculitic rash, lymphadenopathy, serositis with pericardial effusion, and abnormal serum autoantibodies, whereas another had acute nephrotic syndrome. Two of the severely affected patients died in early childhood. Two unrelated patients showed normal psychomotor development until about 13 to 15 months, after which they had acute onset of neurologic regression with loss of motor and intellectual skills and onset of spasticity and dystonia. One patient had a unique phenotype characterized by onset of lower-limb spasticity and acute neurologic deterioration around age 3 years. These changes were associated with brain imaging abnormalities, including cerebral atrophy and deep white matter changes. She developed a multisystem inflammatory disorder with autoantibodies, hair loss, and a livedo rash. Her 33-year-old father had slowly progressive childhood-onset lower-limb spasticity and borderline-positive antinuclear autoantibodies. All patients had laboratory evidence of increased alpha-interferon activity with upregulation of interferon signaling and interferon-stimulated gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24686847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Oda, H., Nakagawa, K., Abe, J., Awaya, T., Funabiki, M., Hijikata, A., Nishikomori, R., Funatsuka, M., Ohshima, Y., Sugawara, Y., Yasumi, T., Kato, H., Shirai, T., Ohara, O., Fujita, T., Heike, T. &lt;strong&gt;Aicardi-Goutieres syndrome is caused by IFIH1 mutations.&lt;/strong&gt; Am. J. Hum. Genet. 95: 121-125, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24995871/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24995871&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24995871[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2014.06.007&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24995871">Oda et al. (2014)</a> reported 3 unrelated Japanese patients with AGS7. Two patients presented around 6 months of age with developmental delay, and the third presented at 4 days of age with omphalitis and thrombocytopenia. Features common to all patients included progressive microcephaly, severe developmental delay beginning in early infancy, and spastic quadriplegia. Two patients had seizures and 2 had dystonia. Laboratory studies showed serum autoantibodies and a type 1 interferon signature. Two patients had hypergammaglobulinemia, hypocomplementemia, thrombocytopenia, and increased serum transaminases. Brain imaging in all children showed basal ganglia calcifications, brain atrophy, and white matter abnormalities. None of the patients developed chilblain lesions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24995871" 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="Buers, I., Rice, G. I., Crow, Y. J., Rutsch, F. &lt;strong&gt;MDA5-associated neuroinflammation and the Singleton-Merten syndrome: two faces of the same type I interferonopathy spectrum.&lt;/strong&gt; J. Interferon Cytokine Res. 37: 214-219, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28475458/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;28475458&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=28475458[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1089/jir.2017.0004&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="28475458">Buers et al. (2017)</a> reported a 6-year-old boy with recurrent febrile episodes, bilateral spasticity, developmental delay, and basal ganglia calcification, and mutation in the IFIH1 gene. Right facial droop was noted at 4 weeks of age. Over the next 6 months he experienced persistent oral mucositis and recurrent ear infections, and later recurrent upper respiratory tract infections. At age 6 months, he developed a pruritic well-defined erythematous lesion on his right flank, which slowly progressed in size; biopsy revealed findings consistent with inflammatory linear verrucous epidermal nevus. Bilateral nephrocalcinosis was noted on abdominal ultrasound. He had failure to thrive with weight loss at 9 months of age, requiring significant caloric supplementation. He had developmental delay, being able to pull and stand at 12 months, but those gross motor milestones were lost at age 15 months, at which time he experienced general muscular hypotonia, worsening of the facial palsy, and a flare of the right flank rash. In the second and third years of life he had recurrent joint pain and stiffness, and over the next several years developed a spastic gait and contractures of the knee joints and elbows. Brain CT scan at age 6 years showed bilateral calcification of the basal ganglia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28475458" 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="Adang, L. A., Frank, D. B., Gilani, A., Takanohashi, A., Ulrick, N., Collins, A., Cross, Z., Galambos, C., Helman, G., Kanaan, U., Keller, S., Simon, D., Sherbini, O., Hanna, B. D., Vanderver, A. L. &lt;strong&gt;Aicardi Goutieres syndrome is associated with pulmonary hypertension.&lt;/strong&gt; Molec. Genet. Metab. 125: 351-358, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30219631/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30219631&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30219631[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2018.09.004&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30219631">Adang et al. (2018)</a> described 3 patients with AGS7 who had typical features of the syndrome but also presented with pulmonary hypertension, 1 at age 16 years, 1 at 7 years, and 1 at 1 month of age. Two of these patients had died. All had gastrointestinal manifestations including hepatitis, poor weight gain, and feeding intolerance, and dermatologic manifestations including vasculitic rashes, psoriasis, and eczema. Two of the 3 had CNS perivascular calcifications. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30219631" 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="#2" class="mim-tip-reference" title="Amari, S., Tsukamoto, K., Ishiguro, A., Yanagi, K., Kaname, T., Ito, Y. &lt;strong&gt;An extremely severe case of Aicardi-Goutieres syndrome 7 with a novel variant in IFIH1.&lt;/strong&gt; Europ. J. Med. Genet. 63: 103646, 2020. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30965144/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30965144&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2019.04.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30965144">Amari et al. (2020)</a> reported a female infant who was found on prenatal ultrasound at 16 weeks' gestation to have a single umbilical artery, intestinal hyperechogenicity, and mitral valve regurgitation. The mitral valve regurgitation resolved spontaneously. However, she was delivered at 29 weeks and 4 days of gestation when prenatal ultrasound showed cardiomegaly, pericardial effusion, splenomegaly, and intracranial calcification. At birth, she was found to have hepatosplenomegaly and 'blueberry muffin' spots on her skin. Laboratory studies showed elevated direct bilirubin and aspartate transaminase levels, anemia, thrombocytopenia, and coagulopathy. Lenticulostriate vasculopathy was seen on head ultrasound. Bilateral cystic periventricular leukomalacia was diagnosed at 20 days of life. She developed pulmonary hypertension, respiratory distress, right-sided heart failure, and ascites. She died at 3 months of age from respiratory failure and pulmonary hypertension. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30965144" 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>
<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. &lt;strong&gt;Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia.&lt;/strong&gt; Neuropediatrics 45: 386-391, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25243380/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25243380&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1055/s-0034-1389161&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25243380">Crow et al. (2014)</a> reported a man, born of unrelated British Caucasian parents, who presented at age 2 years with toe walking associated with slowly progressive spastic paraplegia following normal early psychomotor development. At age 33 years, he showed lower limb spasticity without upper limb involvement. Brain imaging and cognition were normal at the age of 29 years. Exome sequencing identified a de novo heterozygous mutation in the IFIH1 gene (G495R; <a href="/entry/606951#0005">606951.0005</a>) that had been identified in another family with a relatively mild form of AGS7. Laboratory studies revealed persistently 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. &lt;strong&gt;Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia.&lt;/strong&gt; Neuropediatrics 45: 386-391, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25243380/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25243380&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1055/s-0034-1389161&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" 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 heterozygous mutations identified in 5 of the 8 families with AGS7 reported by <a href="#6" class="mim-tip-reference" title="Rice, G. I., del Toro Duany, Y., Jenkinson, E. M., Forte, G. M. A., Anderson, B. H., Ariaudo, G., Bader-Meunier, B., Baildam, E. M., Battini, R., Beresford, M. W., Casarano, M., Chouchane, M., and 41 others. &lt;strong&gt;Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.&lt;/strong&gt; Nature Genet. 46: 503-509, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24686847/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24686847&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24686847[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.2933&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24686847">Rice et al. (2014)</a> occurred de novo; in 2 families, the transmission pattern was consistent with autosomal dominant inheritance and incomplete penetrance, and in 1 family, the parental DNA was not available. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24686847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 8 probands with AGS7, <a href="#6" class="mim-tip-reference" title="Rice, G. I., del Toro Duany, Y., Jenkinson, E. M., Forte, G. M. A., Anderson, B. H., Ariaudo, G., Bader-Meunier, B., Baildam, E. M., Battini, R., Beresford, M. W., Casarano, M., Chouchane, M., and 41 others. &lt;strong&gt;Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.&lt;/strong&gt; Nature Genet. 46: 503-509, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24686847/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24686847&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24686847[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.2933&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24686847">Rice et al. (2014)</a> identified 6 different heterozygous mutations in the IFIH1 gene (<a href="/entry/606951#0001">606951.0001</a>-<a href="/entry/606951#0006">606951.0006</a>). The first 3 mutations were found by whole-exome sequencing. The mutations in 5 of the probands occurred de novo, whereas in 2 they were transmitted; parental DNA was not available for 1 proband. In 1 family, 2 mutation carriers remained clinically unaffected as adults. In vitro functional expression assays in HEK293T cells showed that the mutations caused marked induction of interferon signaling in response to short 162-bp double-stranded RNA (dsRNA), whereas control cells did not. The mutations also conferred 4- to 10-fold higher levels of basal signaling activity even in the absence of exogenous ligand. The mutated residues were located on the surface of the RNA-binding and ATP-binding sites in conserved helicase domains, but ATP hydrolysis activity of the mutants was comparable to wildtype. Structural modeling and biochemical studies indicated that the mutations enhance the stability of the activated IFIH1 filament by increasing affinity for dsRNA. These findings were consistent with a gain of function, resulting in increased interferon signaling. The findings also suggested the presence of an undefined endogenous dsRNA capable of stimulating mutant receptors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24686847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated Japanese patients with AGS7, <a href="#5" class="mim-tip-reference" title="Oda, H., Nakagawa, K., Abe, J., Awaya, T., Funabiki, M., Hijikata, A., Nishikomori, R., Funatsuka, M., Ohshima, Y., Sugawara, Y., Yasumi, T., Kato, H., Shirai, T., Ohara, O., Fujita, T., Heike, T. &lt;strong&gt;Aicardi-Goutieres syndrome is caused by IFIH1 mutations.&lt;/strong&gt; Am. J. Hum. Genet. 95: 121-125, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24995871/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24995871&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24995871[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2014.06.007&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24995871">Oda et al. (2014)</a> identified 3 different de novo heterozygous missense mutations in the IFIH1 gene (<a href="/entry/606951#0002">606951.0002</a>; <a href="/entry/606951#0007">606951.0007</a>; and <a href="/entry/606951#0008">606951.0008</a>). The mutations were found by trio-based whole-exome sequencing. Peripheral blood cells from the patients showed a type 1 interferon signature, and expression of each of the mutations in a human hepatoma cell line resulted in increased activation of the IFNB1 (<a href="/entry/147640">147640</a>) promoter compared to wildtype, consistent with increased type I interferon production. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24995871" 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 6-year-old boy with recurrent febrile episodes, bilateral spasticity, developmental delay, and basal ganglia calcification, <a href="#3" class="mim-tip-reference" title="Buers, I., Rice, G. I., Crow, Y. J., Rutsch, F. &lt;strong&gt;MDA5-associated neuroinflammation and the Singleton-Merten syndrome: two faces of the same type I interferonopathy spectrum.&lt;/strong&gt; J. Interferon Cytokine Res. 37: 214-219, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28475458/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;28475458&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=28475458[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1089/jir.2017.0004&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="28475458">Buers et al. (2017)</a> identified heterozygosity for the recurrent R822Q mutation (<a href="/entry/606951#0009">606951.0009</a>) in the IFIH1 gene, previously reported in patients with Singleton-Merten syndrome (SGMRT1; <a href="/entry/182250">182250</a>). The mutation was not present in parental DNA and was considered to have arisen de novo. The proband's interferon signature pattern showed upregulation of IFN-induced gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28475458" 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="Adang, L. A., Frank, D. B., Gilani, A., Takanohashi, A., Ulrick, N., Collins, A., Cross, Z., Galambos, C., Helman, G., Kanaan, U., Keller, S., Simon, D., Sherbini, O., Hanna, B. D., Vanderver, A. L. &lt;strong&gt;Aicardi Goutieres syndrome is associated with pulmonary hypertension.&lt;/strong&gt; Molec. Genet. Metab. 125: 351-358, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30219631/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30219631&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30219631[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2018.09.004&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30219631">Adang et al. (2018)</a> reported 3 new AGS7 patients with typical features of the disorder and pulmonary hypertension. These 3 patients had missense mutations in the IFIH1 gene that were shown to be de novo in 2 cases. One patient had the previously reported arg337-to-gly (R337G) mutation (<a href="/entry/606951#0003">606951.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30219631" 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 female infant with AGS7, <a href="#2" class="mim-tip-reference" title="Amari, S., Tsukamoto, K., Ishiguro, A., Yanagi, K., Kaname, T., Ito, Y. &lt;strong&gt;An extremely severe case of Aicardi-Goutieres syndrome 7 with a novel variant in IFIH1.&lt;/strong&gt; Europ. J. Med. Genet. 63: 103646, 2020. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30965144/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30965144&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2019.04.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30965144">Amari et al. (2020)</a> identified a de novo heterozygous mutation in the IFIH1 gene (E813D; <a href="/entry/606951#0010">606951.0010</a>). The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30965144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Adang2018" class="mim-anchor"></a>
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Adang, L. A., Frank, D. B., Gilani, A., Takanohashi, A., Ulrick, N., Collins, A., Cross, Z., Galambos, C., Helman, G., Kanaan, U., Keller, S., Simon, D., Sherbini, O., Hanna, B. D., Vanderver, A. L.
<strong>Aicardi Goutieres syndrome is associated with pulmonary hypertension.</strong>
Molec. Genet. Metab. 125: 351-358, 2018.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30219631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30219631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30219631[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=30219631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ymgme.2018.09.004" target="_blank">Full Text</a>]
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<a id="Amari2020" class="mim-anchor"></a>
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Amari, S., Tsukamoto, K., Ishiguro, A., Yanagi, K., Kaname, T., Ito, Y.
<strong>An extremely severe case of Aicardi-Goutieres syndrome 7 with a novel variant in IFIH1.</strong>
Europ. J. Med. Genet. 63: 103646, 2020. Note: Electronic Article.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30965144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30965144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30965144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ejmg.2019.04.003" target="_blank">Full Text</a>]
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<a id="Buers2017" class="mim-anchor"></a>
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Buers, I., Rice, G. I., Crow, Y. J., Rutsch, F.
<strong>MDA5-associated neuroinflammation and the Singleton-Merten syndrome: two faces of the same type I interferonopathy spectrum.</strong>
J. Interferon Cytokine Res. 37: 214-219, 2017.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28475458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28475458</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28475458[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=28475458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1089/jir.2017.0004" target="_blank">Full Text</a>]
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<a id="Crow2014" class="mim-anchor"></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.
<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://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>]
[<a href="https://doi.org/10.1055/s-0034-1389161" target="_blank">Full Text</a>]
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Oda, H., Nakagawa, K., Abe, J., Awaya, T., Funabiki, M., Hijikata, A., Nishikomori, R., Funatsuka, M., Ohshima, Y., Sugawara, Y., Yasumi, T., Kato, H., Shirai, T., Ohara, O., Fujita, T., Heike, T.
<strong>Aicardi-Goutieres syndrome is caused by IFIH1 mutations.</strong>
Am. J. Hum. Genet. 95: 121-125, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24995871/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24995871</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24995871[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=24995871" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ajhg.2014.06.007" target="_blank">Full Text</a>]
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<a id="Rice2014" class="mim-anchor"></a>
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Rice, G. I., del Toro Duany, Y., Jenkinson, E. M., Forte, G. M. A., Anderson, B. H., Ariaudo, G., Bader-Meunier, B., Baildam, E. M., Battini, R., Beresford, M. W., Casarano, M., Chouchane, M., and 41 others.
<strong>Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.</strong>
Nature Genet. 46: 503-509, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24686847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24686847</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24686847[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=24686847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ng.2933" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 05/31/2023
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Hilary J. Vernon - updated : 02/11/2021<br>Ada Hamosh - updated : 01/17/2019<br>Cassandra L. Kniffin - updated : 12/15/2014<br>Cassandra L. Kniffin - updated : 7/24/2014
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alopez : 05/31/2023
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alopez : 03/07/2022<br>ckniffin : 03/03/2022<br>carol : 02/11/2021<br>carol : 01/22/2019<br>carol : 01/18/2019<br>alopez : 01/17/2019<br>carol : 05/22/2017<br>alopez : 12/18/2014<br>mcolton : 12/16/2014<br>ckniffin : 12/15/2014<br>alopez : 7/30/2014<br>mcolton : 7/28/2014<br>ckniffin : 7/24/2014<br>alopez : 6/17/2014<br>mcolton : 6/16/2014<br>ckniffin : 6/12/2014
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<strong>#</strong> 615846
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AICARDI-GOUTIERES SYNDROME 7; AGS7
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<strong>ORPHA:</strong> 51, 689231; &nbsp;
<strong>DO:</strong> 0050629; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Inheritance
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2q24.2
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Aicardi-Goutieres syndrome 7
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615846
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Autosomal dominant
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3
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IFIH1
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606951
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-7 (AGS7) is caused by heterozygous gain-of-function mutation in the IFIH1 gene (606951) on chromosome 2q24.</p>
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<strong>Description</strong>
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<p>Aicardi-Goutieres syndrome-7 (AGS7) is an autosomal dominant inflammatory disorder characterized by severe neurologic impairment. Most patients present in infancy with delayed psychomotor development, axial hypotonia, spasticity, and brain imaging changes, including basal ganglia calcification, cerebral atrophy, and deep white matter abnormalities. Laboratory evaluation shows increased alpha-interferon (IFNA1; 147660) activity with upregulation of interferon signaling and interferon-stimulated gene expression. Some patients may have normal early development followed by episodic neurologic regression (summary by Rice et al., 2014). </p><p>For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750).</p>
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<strong>Clinical Features</strong>
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<p>Rice et al. (2014) reported 8 children with a neurodevelopmental disorder associated with inflammatory markers. Five patients presented with classic clinical features of AGS, including neonatal or infantile onset of growth retardation, irritability, poor feeding, axial hypotonia, and delayed psychomotor development. The most severely affected patients had microcephaly, spastic-dystonic tetraparesis, and lack of speech. Brain imaging showed cerebral atrophy with basal ganglia calcifications and abnormal T2-weighted signal abnormalities in the deep white matter. One patient had a lupus (SLE; 152700)-like disease with vasculitic rash, lymphadenopathy, serositis with pericardial effusion, and abnormal serum autoantibodies, whereas another had acute nephrotic syndrome. Two of the severely affected patients died in early childhood. Two unrelated patients showed normal psychomotor development until about 13 to 15 months, after which they had acute onset of neurologic regression with loss of motor and intellectual skills and onset of spasticity and dystonia. One patient had a unique phenotype characterized by onset of lower-limb spasticity and acute neurologic deterioration around age 3 years. These changes were associated with brain imaging abnormalities, including cerebral atrophy and deep white matter changes. She developed a multisystem inflammatory disorder with autoantibodies, hair loss, and a livedo rash. Her 33-year-old father had slowly progressive childhood-onset lower-limb spasticity and borderline-positive antinuclear autoantibodies. All patients had laboratory evidence of increased alpha-interferon activity with upregulation of interferon signaling and interferon-stimulated gene expression. </p><p>Oda et al. (2014) reported 3 unrelated Japanese patients with AGS7. Two patients presented around 6 months of age with developmental delay, and the third presented at 4 days of age with omphalitis and thrombocytopenia. Features common to all patients included progressive microcephaly, severe developmental delay beginning in early infancy, and spastic quadriplegia. Two patients had seizures and 2 had dystonia. Laboratory studies showed serum autoantibodies and a type 1 interferon signature. Two patients had hypergammaglobulinemia, hypocomplementemia, thrombocytopenia, and increased serum transaminases. Brain imaging in all children showed basal ganglia calcifications, brain atrophy, and white matter abnormalities. None of the patients developed chilblain lesions. </p><p>Buers et al. (2017) reported a 6-year-old boy with recurrent febrile episodes, bilateral spasticity, developmental delay, and basal ganglia calcification, and mutation in the IFIH1 gene. Right facial droop was noted at 4 weeks of age. Over the next 6 months he experienced persistent oral mucositis and recurrent ear infections, and later recurrent upper respiratory tract infections. At age 6 months, he developed a pruritic well-defined erythematous lesion on his right flank, which slowly progressed in size; biopsy revealed findings consistent with inflammatory linear verrucous epidermal nevus. Bilateral nephrocalcinosis was noted on abdominal ultrasound. He had failure to thrive with weight loss at 9 months of age, requiring significant caloric supplementation. He had developmental delay, being able to pull and stand at 12 months, but those gross motor milestones were lost at age 15 months, at which time he experienced general muscular hypotonia, worsening of the facial palsy, and a flare of the right flank rash. In the second and third years of life he had recurrent joint pain and stiffness, and over the next several years developed a spastic gait and contractures of the knee joints and elbows. Brain CT scan at age 6 years showed bilateral calcification of the basal ganglia. </p><p>Adang et al. (2018) described 3 patients with AGS7 who had typical features of the syndrome but also presented with pulmonary hypertension, 1 at age 16 years, 1 at 7 years, and 1 at 1 month of age. Two of these patients had died. All had gastrointestinal manifestations including hepatitis, poor weight gain, and feeding intolerance, and dermatologic manifestations including vasculitic rashes, psoriasis, and eczema. Two of the 3 had CNS perivascular calcifications. </p><p>Amari et al. (2020) reported a female infant who was found on prenatal ultrasound at 16 weeks' gestation to have a single umbilical artery, intestinal hyperechogenicity, and mitral valve regurgitation. The mitral valve regurgitation resolved spontaneously. However, she was delivered at 29 weeks and 4 days of gestation when prenatal ultrasound showed cardiomegaly, pericardial effusion, splenomegaly, and intracranial calcification. At birth, she was found to have hepatosplenomegaly and 'blueberry muffin' spots on her skin. Laboratory studies showed elevated direct bilirubin and aspartate transaminase levels, anemia, thrombocytopenia, and coagulopathy. Lenticulostriate vasculopathy was seen on head ultrasound. Bilateral cystic periventricular leukomalacia was diagnosed at 20 days of life. She developed pulmonary hypertension, respiratory distress, right-sided heart failure, and ascites. She died at 3 months of age from respiratory failure and pulmonary hypertension. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Crow et al. (2014) reported a man, born of unrelated British Caucasian parents, who presented at age 2 years with toe walking associated with slowly progressive spastic paraplegia following normal early psychomotor development. At age 33 years, he showed lower limb spasticity without upper limb involvement. Brain imaging and cognition were normal at the age of 29 years. Exome sequencing identified a de novo heterozygous mutation in the IFIH1 gene (G495R; 606951.0005) that had been identified in another family with a relatively mild form of AGS7. Laboratory studies revealed persistently 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 heterozygous mutations identified in 5 of the 8 families with AGS7 reported by Rice et al. (2014) occurred de novo; in 2 families, the transmission pattern was consistent with autosomal dominant inheritance and incomplete penetrance, and in 1 family, the parental DNA was not available. </p>
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<strong>Molecular Genetics</strong>
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<p>In 8 probands with AGS7, Rice et al. (2014) identified 6 different heterozygous mutations in the IFIH1 gene (606951.0001-606951.0006). The first 3 mutations were found by whole-exome sequencing. The mutations in 5 of the probands occurred de novo, whereas in 2 they were transmitted; parental DNA was not available for 1 proband. In 1 family, 2 mutation carriers remained clinically unaffected as adults. In vitro functional expression assays in HEK293T cells showed that the mutations caused marked induction of interferon signaling in response to short 162-bp double-stranded RNA (dsRNA), whereas control cells did not. The mutations also conferred 4- to 10-fold higher levels of basal signaling activity even in the absence of exogenous ligand. The mutated residues were located on the surface of the RNA-binding and ATP-binding sites in conserved helicase domains, but ATP hydrolysis activity of the mutants was comparable to wildtype. Structural modeling and biochemical studies indicated that the mutations enhance the stability of the activated IFIH1 filament by increasing affinity for dsRNA. These findings were consistent with a gain of function, resulting in increased interferon signaling. The findings also suggested the presence of an undefined endogenous dsRNA capable of stimulating mutant receptors. </p><p>In 3 unrelated Japanese patients with AGS7, Oda et al. (2014) identified 3 different de novo heterozygous missense mutations in the IFIH1 gene (606951.0002; 606951.0007; and 606951.0008). The mutations were found by trio-based whole-exome sequencing. Peripheral blood cells from the patients showed a type 1 interferon signature, and expression of each of the mutations in a human hepatoma cell line resulted in increased activation of the IFNB1 (147640) promoter compared to wildtype, consistent with increased type I interferon production. </p><p>In a 6-year-old boy with recurrent febrile episodes, bilateral spasticity, developmental delay, and basal ganglia calcification, Buers et al. (2017) identified heterozygosity for the recurrent R822Q mutation (606951.0009) in the IFIH1 gene, previously reported in patients with Singleton-Merten syndrome (SGMRT1; 182250). The mutation was not present in parental DNA and was considered to have arisen de novo. The proband's interferon signature pattern showed upregulation of IFN-induced gene expression. </p><p>Adang et al. (2018) reported 3 new AGS7 patients with typical features of the disorder and pulmonary hypertension. These 3 patients had missense mutations in the IFIH1 gene that were shown to be de novo in 2 cases. One patient had the previously reported arg337-to-gly (R337G) mutation (606951.0003). </p><p>In a female infant with AGS7, Amari et al. (2020) identified a de novo heterozygous mutation in the IFIH1 gene (E813D; 606951.0010). The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. </p>
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<strong>REFERENCES</strong>
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Adang, L. A., Frank, D. B., Gilani, A., Takanohashi, A., Ulrick, N., Collins, A., Cross, Z., Galambos, C., Helman, G., Kanaan, U., Keller, S., Simon, D., Sherbini, O., Hanna, B. D., Vanderver, A. L.
<strong>Aicardi Goutieres syndrome is associated with pulmonary hypertension.</strong>
Molec. Genet. Metab. 125: 351-358, 2018.
[PubMed: 30219631]
[Full Text: https://doi.org/10.1016/j.ymgme.2018.09.004]
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Amari, S., Tsukamoto, K., Ishiguro, A., Yanagi, K., Kaname, T., Ito, Y.
<strong>An extremely severe case of Aicardi-Goutieres syndrome 7 with a novel variant in IFIH1.</strong>
Europ. J. Med. Genet. 63: 103646, 2020. Note: Electronic Article.
[PubMed: 30965144]
[Full Text: https://doi.org/10.1016/j.ejmg.2019.04.003]
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Buers, I., Rice, G. I., Crow, Y. J., Rutsch, F.
<strong>MDA5-associated neuroinflammation and the Singleton-Merten syndrome: two faces of the same type I interferonopathy spectrum.</strong>
J. Interferon Cytokine Res. 37: 214-219, 2017.
[PubMed: 28475458]
[Full Text: https://doi.org/10.1089/jir.2017.0004]
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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.
<strong>Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia.</strong>
Neuropediatrics 45: 386-391, 2014.
[PubMed: 25243380]
[Full Text: https://doi.org/10.1055/s-0034-1389161]
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Oda, H., Nakagawa, K., Abe, J., Awaya, T., Funabiki, M., Hijikata, A., Nishikomori, R., Funatsuka, M., Ohshima, Y., Sugawara, Y., Yasumi, T., Kato, H., Shirai, T., Ohara, O., Fujita, T., Heike, T.
<strong>Aicardi-Goutieres syndrome is caused by IFIH1 mutations.</strong>
Am. J. Hum. Genet. 95: 121-125, 2014.
[PubMed: 24995871]
[Full Text: https://doi.org/10.1016/j.ajhg.2014.06.007]
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Rice, G. I., del Toro Duany, Y., Jenkinson, E. M., Forte, G. M. A., Anderson, B. H., Ariaudo, G., Bader-Meunier, B., Baildam, E. M., Battini, R., Beresford, M. W., Casarano, M., Chouchane, M., and 41 others.
<strong>Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.</strong>
Nature Genet. 46: 503-509, 2014.
[PubMed: 24686847]
[Full Text: https://doi.org/10.1038/ng.2933]
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Marla J. F. O&#x27;Neill - updated : 05/31/2023<br>Hilary J. Vernon - updated : 02/11/2021<br>Ada Hamosh - updated : 01/17/2019<br>Cassandra L. Kniffin - updated : 12/15/2014<br>Cassandra L. Kniffin - updated : 7/24/2014
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