2147 lines
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Entry
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- #615651 - LEUKOENCEPHALOPATHY WITH ATAXIA; LKPAT
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- OMIM
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<p>
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<span class="h4">#615651</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/615651"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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<div><a href="https://clinicaltrials.gov/search?cond=LEUKOENCEPHALOPATHY WITH ATAXIA" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=22320&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK326661/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/clcn2-related-leukoencephalopathy" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=615651[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=363540" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 768663003<br />
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<strong>ORPHA:</strong> 363540<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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615651
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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LEUKOENCEPHALOPATHY WITH ATAXIA; LKPAT
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<td>
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<span class="mim-font">
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<a href="/geneMap/3/918?start=-3&limit=10&highlight=918">
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3q27.1
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Leukoencephalopathy with ataxia
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/615651"> 615651 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</td>
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<td>
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<span class="mim-font">
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CLCN2
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/600570"> 600570 </a>
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</span>
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</td>
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</tbody>
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</table>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/615651" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/615651" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/615651" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
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</span>
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</div>
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<div>
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<span class="h5 mim-font">
|
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<strong> HEAD & NECK </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Eyes </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Visual field defects (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12184005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12184005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/368.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.40</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/368.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3887875&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887875</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001123</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001123</a>]</span><br /> -
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Chorioretinopathy (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302893000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302893000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0339383&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0339383</a>]</span><br /> -
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Optic neuropathy (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/77157004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">77157004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029132&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029132</a>, <a href="https://bioportal.bioontology.org/search?q=C3887709&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887709</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001138" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001138</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001138" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001138</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Gait ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25136009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25136009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R26.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R26.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span><br /> -
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Limb ataxia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0750937&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0750937</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002070" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002070</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002070" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002070</a>]</span><br /> -
|
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Headache <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25064002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25064002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R51.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R51.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R51</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/784.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018681&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018681</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002315</a>]</span><br /> -
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Learning disabilities (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1855002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1855002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F81.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F81.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751265&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751265</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001328" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001328</a>]</span><br /> -
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Leukoencephalopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22811006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22811006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16058431000119104" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16058431000119104</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0270612&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0270612</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002352" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002352</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002352" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002352</a>]</span><br /> -
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Signal abnormalities in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3810243&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3810243</a>]</span><br /> -
|
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Low apparent diffusion coefficient (ADC) values <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3810244&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3810244</a>]</span><br /> -
|
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Diffuse hyperintense signal abnormalities in the white matter (in children) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3810245&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3810245</a>]</span><br /> -
|
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Myelin microvacuolation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3810246&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3810246</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Two peaks of onset, childhood and adult<br /> -
|
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Variable clinical features<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> MOLECULAR BASIS </strong>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the chloride channel 2 gene (CLCN2, <a href="/entry/600570#0006">600570.0006</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
|
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that leukoencephalopathy with ataxia (LKPAT) is caused by homozygous or compound heterozygous mutation in the CLCN2 gene (<a href="/entry/600570">600570</a>) on chromosome 3q27.</p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Leukoencephalopathy with ataxia is an autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient (ADC) values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles. The findings suggest myelin microvacuolation restricted to certain brain regions. Clinical features include ataxia and unstable gait; more variable abnormalities may include visual field defects, headaches, and learning disabilities (summary by <a href="#3" class="mim-tip-reference" title="Depienne, C., Bugiani, M., Dupuits, C., Galanaud, D., Touitou, V., Postma, N., van Berkel, C., Polder, E., Tollard, E., Darios, F., Brice, A., de Die-Smulders, C. E., and 12 others. <strong>Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.</strong> Lancet Neurol. 12: 659-668, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707145</a>] [<a href="https://doi.org/10.1016/S1474-4422(13)70053-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23707145">Depienne et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="clinicalFeatures" class="mim-anchor"></a>
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<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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</div>
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<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p><a href="#3" class="mim-tip-reference" title="Depienne, C., Bugiani, M., Dupuits, C., Galanaud, D., Touitou, V., Postma, N., van Berkel, C., Polder, E., Tollard, E., Darios, F., Brice, A., de Die-Smulders, C. E., and 12 others. <strong>Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.</strong> Lancet Neurol. 12: 659-668, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707145</a>] [<a href="https://doi.org/10.1016/S1474-4422(13)70053-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23707145">Depienne et al. (2013)</a> reported 6 unrelated patients with a characteristic pattern of leukoencephalopathy on brain MRI, including 3 with adult onset and 3 with childhood onset of the disorder. Clinical features overlapped, but were variable. The adult patients had mild cerebellar ataxia with a variable combination of chorioretinopathy, visual field defects, optic neuropathy, and headaches. One patient had a schizophrenia-like disorder. The children had mild cerebellar ataxia and a variable combination of mild spasticity, visual field defects, learning disabilities, and headaches. None of the patients had seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707145" 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>Neuroradiologic Features</em></strong></p><p>
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Brain MRI of all 6 patients with leukoencephalopathy and ataxia reported by <a href="#3" class="mim-tip-reference" title="Depienne, C., Bugiani, M., Dupuits, C., Galanaud, D., Touitou, V., Postma, N., van Berkel, C., Polder, E., Tollard, E., Darios, F., Brice, A., de Die-Smulders, C. E., and 12 others. <strong>Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.</strong> Lancet Neurol. 12: 659-668, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707145</a>] [<a href="https://doi.org/10.1016/S1474-4422(13)70053-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23707145">Depienne et al. (2013)</a> showed prominent signal abnormalities in the middle cerebellar peduncles, midbrain cerebral peduncles, pyramidal tracts in the pons, and posterior limbs of the internal capsule. There were additional abnormalities in specific brainstem tracts and the cerebellar white matter. ADC values were decreased in all patients, indicating small water spaces within tissue microstructure. The pediatric patients also had diffuse mild signal abnormalities of the white matter, which were hyperintense compared to gray matter on T2- and T1-weighted images. These changes suggested myelin microvacuolation rather than hypomyelination. <a href="#3" class="mim-tip-reference" title="Depienne, C., Bugiani, M., Dupuits, C., Galanaud, D., Touitou, V., Postma, N., van Berkel, C., Polder, E., Tollard, E., Darios, F., Brice, A., de Die-Smulders, C. E., and 12 others. <strong>Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.</strong> Lancet Neurol. 12: 659-668, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707145</a>] [<a href="https://doi.org/10.1016/S1474-4422(13)70053-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23707145">Depienne et al. (2013)</a> noted that the clinical features of these patients were nonspecific and did not allow a diagnosis, whereas the MRI findings were specific enough to allow a diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of leukoencephalopathy with ataxia in the families reported by <a href="#3" class="mim-tip-reference" title="Depienne, C., Bugiani, M., Dupuits, C., Galanaud, D., Touitou, V., Postma, N., van Berkel, C., Polder, E., Tollard, E., Darios, F., Brice, A., de Die-Smulders, C. E., and 12 others. <strong>Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.</strong> Lancet Neurol. 12: 659-668, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707145</a>] [<a href="https://doi.org/10.1016/S1474-4422(13)70053-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23707145">Depienne et al. (2013)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707145" 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 6 unrelated patients with LKPAT, <a href="#3" class="mim-tip-reference" title="Depienne, C., Bugiani, M., Dupuits, C., Galanaud, D., Touitou, V., Postma, N., van Berkel, C., Polder, E., Tollard, E., Darios, F., Brice, A., de Die-Smulders, C. E., and 12 others. <strong>Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.</strong> Lancet Neurol. 12: 659-668, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707145</a>] [<a href="https://doi.org/10.1016/S1474-4422(13)70053-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23707145">Depienne et al. (2013)</a> identified homozygous or compound heterozygous mutations in the CLCN2 gene (see, e.g., <a href="/entry/600570#0006">600570.0006</a>-<a href="/entry/600570#0009">600570.0009</a>). The first mutations were found by whole-exome sequencing. CLCN2, which is involved in brain ion and water homeostasis, was detected in astrocytes and all components of the panglial syncytium. CLCN2 was also enriched in astrocytic endfeet at the perivascular basal lamina, in the glia limitans, and in ependymal cells. All mutations were shown to cause a loss of protein function. The clinical findings were similar to those observed in Clcn2-deficient mice (see ANIMAL MODEL). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Bosl, M. R., Stein, V., Hubner, C., Zdebik, A. A., Jordt, S.-E., Mukhopadhyay, A. K., Davidoff, M. S., Holstein, A.-F., Jentsch, T. J. <strong>Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption.</strong> EMBO J. 20: 1289-1299, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11250895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11250895</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11250895[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/20.6.1289" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11250895">Bosl et al. (2001)</a> found that Clcn2-null mice developed severe degeneration of the retina and the testes, which led to selective male infertility. Seminiferous tubules did not develop lumina, and germ cells failed to complete meiosis. In the retina, photoreceptors lacked normal outer segments and degenerated between days P10 and P30. The current across the retinal pigment epithelium was severely reduced at P36. Thus, Clcn2 disruption resulted in the death of 2 cell types that depend on supporting cells that form the blood-testes and blood-retina barriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11250895" 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="Blanz, J., Schweizer, M., Auberson, M., Maier, H., Muenscher, A., Hubner, C. A., Jentsch, T. J. <strong>Leukoencephalopathy upon disruption of the chloride channel Clc-2.</strong> J. Neurosci. 27: 6581-6589, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17567819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17567819</a>] [<a href="https://doi.org/10.1523/JNEUROSCI.0338-07.2007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17567819">Blanz et al. (2007)</a> found that Clcn2-null mice were blind and developed progressive widespread spongiform vacuolation of white matter in the brain and spinal cord. Fluid-filled spaces appeared between myelin sheaths of the central but not the peripheral nervous system. However, neuronal morphology appeared normal, and neurologic deficits were mild, mainly including decreased conduction velocity in neurons of the central auditory pathway. The phenotype resembled a leukodystrophy; however, no CLCN2 mutations were found in 150 human leukodystrophy patients. Heterozygous loss of Clcn2 had no detectable functional or morphologic consequences. Neither heterozygous nor homozygous Clcn2 knockout mice had lowered seizure thresholds. <a href="#1" class="mim-tip-reference" title="Blanz, J., Schweizer, M., Auberson, M., Maier, H., Muenscher, A., Hubner, C. A., Jentsch, T. J. <strong>Leukoencephalopathy upon disruption of the chloride channel Clc-2.</strong> J. Neurosci. 27: 6581-6589, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17567819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17567819</a>] [<a href="https://doi.org/10.1523/JNEUROSCI.0338-07.2007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17567819">Blanz et al. (2007)</a> postulated a role for CLCN2 in glial function and ionic homeostasis in the central nervous system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17567819" 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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Blanz, J., Schweizer, M., Auberson, M., Maier, H., Muenscher, A., Hubner, C. A., Jentsch, T. J.
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<strong>Leukoencephalopathy upon disruption of the chloride channel Clc-2.</strong>
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J. Neurosci. 27: 6581-6589, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17567819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17567819</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17567819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1523/JNEUROSCI.0338-07.2007" target="_blank">Full Text</a>]
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Bosl, M. R., Stein, V., Hubner, C., Zdebik, A. A., Jordt, S.-E., Mukhopadhyay, A. K., Davidoff, M. S., Holstein, A.-F., Jentsch, T. J.
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<strong>Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption.</strong>
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EMBO J. 20: 1289-1299, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11250895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11250895</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11250895[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=11250895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Depienne, C., Bugiani, M., Dupuits, C., Galanaud, D., Touitou, V., Postma, N., van Berkel, C., Polder, E., Tollard, E., Darios, F., Brice, A., de Die-Smulders, C. E., and 12 others.
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<strong>Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.</strong>
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Lancet Neurol. 12: 659-668, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/S1474-4422(13)70053-X" target="_blank">Full Text</a>]
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Creation Date:
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Cassandra L. Kniffin : 2/17/2014
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carol : 07/18/2017
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carol : 02/19/2014<br>mcolton : 2/19/2014<br>ckniffin : 2/19/2014
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LEUKOENCEPHALOPATHY WITH ATAXIA; LKPAT
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<strong>SNOMEDCT:</strong> 768663003;
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<strong>ORPHA:</strong> 363540;
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<strong>Phenotype-Gene Relationships</strong>
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<tbody>
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<span class="mim-font">
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3q27.1
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</span>
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<td>
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<span class="mim-font">
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Leukoencephalopathy with ataxia
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</span>
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</td>
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<td>
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<span class="mim-font">
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615651
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<td>
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<span class="mim-font">
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Autosomal recessive
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</td>
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<td>
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<span class="mim-font">
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3
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<td>
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<span class="mim-font">
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CLCN2
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<td>
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<span class="mim-font">
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600570
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that leukoencephalopathy with ataxia (LKPAT) is caused by homozygous or compound heterozygous mutation in the CLCN2 gene (600570) on chromosome 3q27.</p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Leukoencephalopathy with ataxia is an autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient (ADC) values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles. The findings suggest myelin microvacuolation restricted to certain brain regions. Clinical features include ataxia and unstable gait; more variable abnormalities may include visual field defects, headaches, and learning disabilities (summary by Depienne et al., 2013). </p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Depienne et al. (2013) reported 6 unrelated patients with a characteristic pattern of leukoencephalopathy on brain MRI, including 3 with adult onset and 3 with childhood onset of the disorder. Clinical features overlapped, but were variable. The adult patients had mild cerebellar ataxia with a variable combination of chorioretinopathy, visual field defects, optic neuropathy, and headaches. One patient had a schizophrenia-like disorder. The children had mild cerebellar ataxia and a variable combination of mild spasticity, visual field defects, learning disabilities, and headaches. None of the patients had seizures. </p><p><strong><em>Neuroradiologic Features</em></strong></p><p>
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Brain MRI of all 6 patients with leukoencephalopathy and ataxia reported by Depienne et al. (2013) showed prominent signal abnormalities in the middle cerebellar peduncles, midbrain cerebral peduncles, pyramidal tracts in the pons, and posterior limbs of the internal capsule. There were additional abnormalities in specific brainstem tracts and the cerebellar white matter. ADC values were decreased in all patients, indicating small water spaces within tissue microstructure. The pediatric patients also had diffuse mild signal abnormalities of the white matter, which were hyperintense compared to gray matter on T2- and T1-weighted images. These changes suggested myelin microvacuolation rather than hypomyelination. Depienne et al. (2013) noted that the clinical features of these patients were nonspecific and did not allow a diagnosis, whereas the MRI findings were specific enough to allow a diagnosis. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The transmission pattern of leukoencephalopathy with ataxia in the families reported by Depienne et al. (2013) was consistent with autosomal recessive inheritance. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 6 unrelated patients with LKPAT, Depienne et al. (2013) identified homozygous or compound heterozygous mutations in the CLCN2 gene (see, e.g., 600570.0006-600570.0009). The first mutations were found by whole-exome sequencing. CLCN2, which is involved in brain ion and water homeostasis, was detected in astrocytes and all components of the panglial syncytium. CLCN2 was also enriched in astrocytic endfeet at the perivascular basal lamina, in the glia limitans, and in ependymal cells. All mutations were shown to cause a loss of protein function. The clinical findings were similar to those observed in Clcn2-deficient mice (see ANIMAL MODEL). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bosl et al. (2001) found that Clcn2-null mice developed severe degeneration of the retina and the testes, which led to selective male infertility. Seminiferous tubules did not develop lumina, and germ cells failed to complete meiosis. In the retina, photoreceptors lacked normal outer segments and degenerated between days P10 and P30. The current across the retinal pigment epithelium was severely reduced at P36. Thus, Clcn2 disruption resulted in the death of 2 cell types that depend on supporting cells that form the blood-testes and blood-retina barriers. </p><p>Blanz et al. (2007) found that Clcn2-null mice were blind and developed progressive widespread spongiform vacuolation of white matter in the brain and spinal cord. Fluid-filled spaces appeared between myelin sheaths of the central but not the peripheral nervous system. However, neuronal morphology appeared normal, and neurologic deficits were mild, mainly including decreased conduction velocity in neurons of the central auditory pathway. The phenotype resembled a leukodystrophy; however, no CLCN2 mutations were found in 150 human leukodystrophy patients. Heterozygous loss of Clcn2 had no detectable functional or morphologic consequences. Neither heterozygous nor homozygous Clcn2 knockout mice had lowered seizure thresholds. Blanz et al. (2007) postulated a role for CLCN2 in glial function and ionic homeostasis in the central nervous system. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
|
Blanz, J., Schweizer, M., Auberson, M., Maier, H., Muenscher, A., Hubner, C. A., Jentsch, T. J.
|
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<strong>Leukoencephalopathy upon disruption of the chloride channel Clc-2.</strong>
|
|
J. Neurosci. 27: 6581-6589, 2007.
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[PubMed: 17567819]
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[Full Text: https://doi.org/10.1523/JNEUROSCI.0338-07.2007]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Bosl, M. R., Stein, V., Hubner, C., Zdebik, A. A., Jordt, S.-E., Mukhopadhyay, A. K., Davidoff, M. S., Holstein, A.-F., Jentsch, T. J.
|
|
<strong>Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption.</strong>
|
|
EMBO J. 20: 1289-1299, 2001.
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[PubMed: 11250895]
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[Full Text: https://doi.org/10.1093/emboj/20.6.1289]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Depienne, C., Bugiani, M., Dupuits, C., Galanaud, D., Touitou, V., Postma, N., van Berkel, C., Polder, E., Tollard, E., Darios, F., Brice, A., de Die-Smulders, C. E., and 12 others.
|
|
<strong>Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study.</strong>
|
|
Lancet Neurol. 12: 659-668, 2013.
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[PubMed: 23707145]
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[Full Text: https://doi.org/10.1016/S1474-4422(13)70053-X]
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</p>
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</li>
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</ol>
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<br />
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin : 2/17/2014
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</span>
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</div>
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Edit History:
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<span class="mim-text-font">
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carol : 07/18/2017<br>carol : 02/19/2014<br>mcolton : 2/19/2014<br>ckniffin : 2/19/2014
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