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<title>
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Entry
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- #619224 - MITOCHONDRIAL COMPLEX II DEFICIENCY, NUCLEAR TYPE 4; MC2DN4
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- OMIM
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<span class="h4">#619224</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/619224"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS252011"> <strong>Phenotypic Series</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="#references"><strong>References</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(MITOCHONDRIAL COMPLEX II DEFICIENCY, NUCLEAR TYPE) OR (SDHB)" class="mim-tip-hint" title="Clinical Trials" 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=3377&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/gtr/all/tests/?term=619224[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=3208" 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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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 3208<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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619224
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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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MITOCHONDRIAL COMPLEX II DEFICIENCY, NUCLEAR TYPE 4; MC2DN4
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<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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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
|
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<span class="mim-font">
|
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<a href="/geneMap/1/209?start=-3&limit=10&highlight=209">
|
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1p36.13
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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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Mitochondrial complex II deficiency, nuclear type 4
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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/619224"> 619224 </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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</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="3 - The molecular basis of the disorder is known"> 3 </abbr>
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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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SDHB
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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/185470"> 185470 </a>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/619224" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS252011" class="btn btn-info" role="button"> Phenotypic Series </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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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/619224" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/619224" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> HEAD & NECK </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> 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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|
|
- Optic atrophy (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br /> -
|
|
Nystagmus (in 1 patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </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> Heart </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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|
|
- Cardiomyopathy (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85898001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85898001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57809008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57809008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I51.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I51.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0878544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0878544</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001638" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001638</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001638" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001638</a>]</span><br />
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</span>
|
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</div>
|
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </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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|
|
- Respiratory failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409622000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409622000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J96.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J96.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1145670&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1145670</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002878</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002878</a>]</span><br />
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|
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</span>
|
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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|
|
|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Developmental regression <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/609225004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">609225004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836830&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836830</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002376" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002376</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002376" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002376</a>]</span><br /> -
|
|
Cognitive impairment <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386806002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386806002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0338656&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0338656</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>]</span><br /> -
|
|
Encephalopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/81308009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">81308009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G93.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G93.40</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/348.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.30</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/348.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085584&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085584</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001298" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001298</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001298" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001298</a>]</span><br /> -
|
|
Seizures (in 1 patient) <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 /> -
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|
Ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20262006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20262006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39384006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39384006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R27.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R27.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004134&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004134</a>, <a href="https://bioportal.bioontology.org/search?q=C1135207&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1135207</a>, <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0010867" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010867</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
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Truncal hypotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853743&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853743</a> 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> <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 /> -
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Appendicular hypertonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1838391&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1838391</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002509" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002509</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002509" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002509</a>]</span><br /> -
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Elevated lactate seen on magnetic resonance spectroscopy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5543170&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5543170</a>]</span><br /> -
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Elevated succinate seen on magnetic resonance spectroscopy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5543177&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5543177</a>]</span><br /> -
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Abnormalities of the hemispheric white matter with sparing of subcortical U fibers seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5543178&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5543178</a>]</span><br /> -
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Abnormalities of the thalamus seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5543179&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5543179</a>]</span><br /> -
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Abnormalities of the corpus callosum seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5543180&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5543180</a>]</span><br /> -
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Abnormalities of the spinal cord seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5543181&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5543181</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> LABORATORY ABNORMALITIES </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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- Elevated blood lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5543172&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5543172</a>]</span><br /> -
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Elevated CSF lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5543182&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5543182</a>]</span><br /> -
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Elevated urine ketones (some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5543183&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5543183</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> 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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- Developmental regression triggered by illness<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 mutations in the succinate dehydrogenase complex, subunit B gene (SDHB, <a href="/entry/185470#0001">185470.0001</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 id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small">
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<div class="row">
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<h5>
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Mitochondrial complex II deficiency, nuclear type
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- <a href="/phenotypicSeries/PS252011">PS252011</a>
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- 4 Entries
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</h5>
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</div>
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</div>
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<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
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<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
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<thead>
|
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<tr>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Location</strong>
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</th>
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
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<strong>Phenotype</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Inheritance</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />mapping key</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />MIM number</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Gene/Locus</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Gene/Locus<br />MIM number</strong>
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
|
|
<tr>
|
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<td>
|
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<span class="mim-font">
|
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|
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<a href="/geneMap/1/209?start=-3&limit=10&highlight=209"> 1p36.13 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/619224"> Mitochondrial complex II deficiency, nuclear type 4 </a>
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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|
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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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|
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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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|
|
</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/619224"> 619224 </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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<a href="/entry/185470"> SDHB </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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<a href="/entry/185470"> 185470 </a>
|
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</span>
|
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</td>
|
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</tr>
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<tr>
|
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<td>
|
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<span class="mim-font">
|
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|
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<a href="/geneMap/5/9?start=-3&limit=10&highlight=9"> 5p15.33 </a>
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|
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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/252011"> Mitochondrial complex II deficiency, nuclear type 1 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/252011"> 252011 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600857"> SDHA </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600857"> 600857 </a>
|
|
</span>
|
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</td>
|
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</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/930?start=-3&limit=10&highlight=930"> 11q23.1 </a>
|
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|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619167"> Mitochondrial complex II deficiency, nuclear type 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/619167"> 619167 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602690"> SDHD </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602690"> 602690 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/609?start=-3&limit=10&highlight=609"> 19q13.12 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619166"> Mitochondrial complex II deficiency, nuclear type 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/619166"> 619166 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612848"> SDHAF1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612848"> 612848 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
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|
|
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|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
|
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|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
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|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<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.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</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 mitochondrial complex II deficiency nuclear type 4 (MC2DN4) is caused by homozygous or compound heterozygous mutation in the succinate dehydrogenase complex subunit B gene (SDHB; <a href="/entry/185470">185470</a>) on chromosome 1p36.</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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|
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<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
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</h4>
|
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</div>
|
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|
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<div id="mimDescriptionFold" class="collapse in ">
|
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<span class="mim-text-font">
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<p>Mitochondrial complex II deficiency nuclear type 4 (MC2DN4) is a severe autosomal recessive disorder characterized by early-onset progressive neurodegeneration with leukoencephalopathy. Acute episodes of neurodegeneration are often triggered by catabolic stress such as infection or fasting.</p>
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<p><a href="#1" class="mim-tip-reference" title="Alston, C. L., Davison, J. E., Meloni, F., van der Westhuizen, F. H., He, L., Hornig-Do, H.-T., Peet, A. C., Gissen, P., Goffrini, P., Ferrero, I., Wassmer, E., McFarland, R., Taylor, R. W. <strong>Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency.</strong> J. Med. Genet. 49: 569-577, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22972948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22972948</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22972948[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/10.1136/jmedgenet-2012-101146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22972948">Alston et al. (2012)</a> reported an Asian girl, born of consanguineous parents, with neurologic impairment, leukoencephalopathy, and biochemical evidence of mitochondrial complex II deficiency. The patient showed developmental regression beginning at age 1 year. She was hypotonic with joint contractures, and she became wheelchair-bound at age 4 years. Brain MRI showed leukodystrophy in the deep white matter and signal abnormalities in the corpus callosum. MR spectroscopy showed increased lactate and increased succinate in the dystrophic white matter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22972948" 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="Ardissone, A., Invernizzi, F., Nasca, A., Moroni, I., Farina, L., Ghezzi, D. <strong>Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance.</strong> Molec. Genet. Metab. Rep. 5: 51-54, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26925370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26925370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26925370[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/10.1016/j.ymgmr.2015.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26925370">Ardissone et al. (2015)</a> reported a Pakistani girl who presented at 15 months of age with acute psychomotor depression that developed several days after a febrile illness. On evaluation one month later, she had general hypotonia, hyperreflexia, lack of postural control, and irritability. Laboratory studies showed elevated plasma lactate and pyruvate and elevated 2-ketoglutarate in the urine. Brain MRI showed diffuse hyperintensity of the hemispheric white matter and corpus callosum with sparing of the subcortical U-fibers, hyperintensities of the bilateral thalami, and cystic degeneration of the deep white matter. HNMR-spectroscopy revealed succinate and lactate peaks. Visual evoked potential testing showed central conduction abnormalities. Her healthy 11-year-old sib had the same homozygous mutation in the SDHB gene (D48V; <a href="/entry/185470#0020">185470.0020</a>), leading <a href="#2" class="mim-tip-reference" title="Ardissone, A., Invernizzi, F., Nasca, A., Moroni, I., Farina, L., Ghezzi, D. <strong>Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance.</strong> Molec. Genet. Metab. Rep. 5: 51-54, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26925370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26925370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26925370[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/10.1016/j.ymgmr.2015.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26925370">Ardissone et al. (2015)</a> to hypothesize that triggering stimuli may have been necessary to produce a clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26925370" 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="#7" class="mim-tip-reference" title="Vanderver, A., Simons, C., Helman, G., Crawford, J., Wolf, N. I., Bernard, G., Pizzino, A., Schmidt, J. L., Takanohashi, A., Miller, D., Khouzam, A., Rajan, V., and 17 others. <strong>Whole exome sequencing in patients with white matter abnormalities.</strong> Ann. Neurol. 79: 1031-1037, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27159321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27159321</a>] [<a href="https://doi.org/10.1002/ana.24650" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27159321">Vanderver et al. (2016)</a> reported a Turkish boy (patient LD_0756.0A), born of consanguineous parents, who had motor delays from birth and acutely decompensated at 7 months of age. He had ataxia, hypotonia, and spasticity. Brain MRI at 3.5 years of age showed abnormal signal in the supratentorial white matter with sparing of the U-fibers, a swollen appearance of the corpus callosum, and involvement of the cerebellar white matter of the brainstem. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27159321" 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="Helman, G., Caldovic, L., Whitehead, M. T., Simons, C., Brockmann, K., Edvardson, S., Bai, R., Moroni, I., Taylor, J. M., Van Haren K., SDH Study Group, Taft, R. J., Vanderver, A., van der Knaap, M. S. <strong>Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy.</strong> Ann. Neurol. 79: 379-386, 2016. Note: Erratum: Ann. Neurol. 84: 481 only, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26642834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26642834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26642834[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/10.1002/ana.24572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26642834">Helman et al. (2016)</a> reported clinical and radiologic features in 5 patients, 4 of whom were living (patients 10, 11, 16 and 19) with an age range of 19 months to 9 years, and one of whom died at 1 year of age from respiratory failure (patient 15). Age of onset of symptoms ranged from birth to 18 months. In the 4 patients who had an MRI within the first 2 years of life, all had involvement of the corpus callosum and the thalamic nuclei, 3 had involvement of the middle cerebellar peduncles and pons, 3 had involvement of the spinal cord, 3 had involvement of the corticospinal tracts, and 2 had involvement of the cerebellar white matter. Patient 10 had spastic tetraparesis and normal cognition. Patient 11 had dilated cardiomyopathy with significant hypertrophy and poor function, gross motor impairment with contractures, and intact cognition. Patient 16 had spastic diplegia with severe motor difficulties and severe cognitive impairment. Patient 19 had generalized hypotonia, lack of postural control, irritability, and moderate cognitive impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26642834" 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="#4" class="mim-tip-reference" title="Gronborg, S., Darin, N., Miranda, M. J., Damgaard, B., Cayuela, J. A., Oldfors, A., Kollberg, G., Hansen, T. V. O., Ravn, K., Wibrand, F., Ostergaard, E. <strong>Leukoencephalopathy due to complex II deficiency and bi-allelic SDHB mutations: further cases and implications for genetic counselling.</strong> JIMD Rep. 33: 69-77, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27604842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27604842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27604842[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/10.1007/8904_2016_582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27604842">Gronborg et al. (2017)</a> reported 2 unrelated patients with complex II deficiency. Patient 1, a Lebanese girl born to consanguineous parents, had slight developmental delay and hypotonia in the first year of life. She then had a progressive loss of developmental milestones starting at age 12 months, which was more pronounced during infections. At age 15 months, she had truncal hypotonia and increased muscle tone and increased reflexes in the limbs. She had slight bilateral optic atrophy, reduced vision, and horizontal nystagmus with opsoclonus. Brain MRI at age 16 months showed signal intensities in the frontal, parietooccipital, and posterior temporal white matter with sparing of the juxtacortical fibers. Laboratory studies showed an increased blood lactate and increased ketones and Krebs cycle intermediates (especially succinate) in the urine. She died at age 25 months of multiorgan failure in the setting of a respiratory infection. Patient 2, a boy born of nonconsanguineous parents, had intrauterine growth retardation, with decreased head circumference, length, and weight at birth. Starting at age 6 months, he had progressive loss of acquired skills, which was worse during infections. At age 9 months, he had pneumonia and respiratory failure necessitating assisted ventilation, and he had further loss of developmental skills. Laboratory studies showed increased blood lactate, increased ALAT and ASAT, increased creatine kinase, and increased INR. He had cardiomyopathy with severe dilatation and hypertrophy of the septum and posterior wall of the left ventricle. MRI at age 11 months showed signal intensities in the frontal, parietooccipital, and posterior temporal white matter with sparing of the juxtacortical fibers. He was stable with some improvement until 1 year of age when he died from multiorgan failure and cardiac arrest. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27604842" 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="#6" class="mim-tip-reference" title="Kaur, P., Sharma, S., Kadavigere, R., Girisha K. M., Shukla, A. <strong>Novel variant p.(Ala102Thr) in SDHB causes mitochondrial complex II deficiency: case report and review of the literature.</strong> Ann. Hum. Genet. 84: 345-351, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32124427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32124427</a>] [<a href="https://doi.org/10.1111/ahg.12377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32124427">Kaur et al. (2020)</a> reported an Indian boy who had regression of milestones at 1 year of age. He developed febrile seizures at age 18 months. On examination, he had increased tone in all limbs and brisk deep tendon reflexes. Ophthalmologic examination revealed bilateral optic atrophy. Brain MRI showed confluent lesions in the periventricular white matter, corpus callosum, dorsomedial thalami, brainstem, and spinal cord. Plasma and CSF lactate were elevated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32124427" 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 MC2DN4 in the patients reported by <a href="#1" class="mim-tip-reference" title="Alston, C. L., Davison, J. E., Meloni, F., van der Westhuizen, F. H., He, L., Hornig-Do, H.-T., Peet, A. C., Gissen, P., Goffrini, P., Ferrero, I., Wassmer, E., McFarland, R., Taylor, R. W. <strong>Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency.</strong> J. Med. Genet. 49: 569-577, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22972948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22972948</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22972948[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/10.1136/jmedgenet-2012-101146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22972948">Alston et al. (2012)</a> and <a href="#2" class="mim-tip-reference" title="Ardissone, A., Invernizzi, F., Nasca, A., Moroni, I., Farina, L., Ghezzi, D. <strong>Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance.</strong> Molec. Genet. Metab. Rep. 5: 51-54, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26925370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26925370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26925370[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/10.1016/j.ymgmr.2015.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26925370">Ardissone et al. (2015)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26925370+22972948" 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 an Asian girl, born of consanguineous parents, with neurologic impairment, leukoencephalopathy, and biochemical evidence of mitochondrial complex II deficiency, <a href="#1" class="mim-tip-reference" title="Alston, C. L., Davison, J. E., Meloni, F., van der Westhuizen, F. H., He, L., Hornig-Do, H.-T., Peet, A. C., Gissen, P., Goffrini, P., Ferrero, I., Wassmer, E., McFarland, R., Taylor, R. W. <strong>Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency.</strong> J. Med. Genet. 49: 569-577, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22972948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22972948</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22972948[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/10.1136/jmedgenet-2012-101146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22972948">Alston et al. (2012)</a> identified a homozygous missense mutation in the SDHB gene (D48V; <a href="/entry/185470#0020">185470.0020</a>). Her unaffected parents were heterozygous for the mutation. Patient fibroblasts showed decreased amounts of fully assembled complex II and almost complete absence of the SDHB subunit. Complex II activity was also decreased in patient muscle samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22972948" 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 Pakistani girl, born to consanguineous parents, with MC2DN4, <a href="#2" class="mim-tip-reference" title="Ardissone, A., Invernizzi, F., Nasca, A., Moroni, I., Farina, L., Ghezzi, D. <strong>Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance.</strong> Molec. Genet. Metab. Rep. 5: 51-54, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26925370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26925370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26925370[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/10.1016/j.ymgmr.2015.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26925370">Ardissone et al. (2015)</a> identified homozygosity for the previously reported D48V mutation in the SDHB gene. The mutation was found by sequencing of a panel of 7 genes associated with complex II deficiency. A clinically unaffected sib was also homozygous for the mutation. SDHB protein expression was reduced in patient fibroblasts and lymphocytes as well as in lymphocytes from the clinically unaffected sib. SDHA protein was also reduced in these cells, possibly due to instability of complex II assembly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26925370" 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 Turkish boy, born of consanguineous parents, with MC2DN4, <a href="#7" class="mim-tip-reference" title="Vanderver, A., Simons, C., Helman, G., Crawford, J., Wolf, N. I., Bernard, G., Pizzino, A., Schmidt, J. L., Takanohashi, A., Miller, D., Khouzam, A., Rajan, V., and 17 others. <strong>Whole exome sequencing in patients with white matter abnormalities.</strong> Ann. Neurol. 79: 1031-1037, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27159321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27159321</a>] [<a href="https://doi.org/10.1002/ana.24650" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27159321">Vanderver et al. (2016)</a> identified homozygosity for the D48V mutation in the SDHB gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27159321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 6 patients with MC2DN4, <a href="#5" class="mim-tip-reference" title="Helman, G., Caldovic, L., Whitehead, M. T., Simons, C., Brockmann, K., Edvardson, S., Bai, R., Moroni, I., Taylor, J. M., Van Haren K., SDH Study Group, Taft, R. J., Vanderver, A., van der Knaap, M. S. <strong>Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy.</strong> Ann. Neurol. 79: 379-386, 2016. Note: Erratum: Ann. Neurol. 84: 481 only, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26642834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26642834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26642834[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/10.1002/ana.24572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26642834">Helman et al. (2016)</a> identified mutations in the SDHB gene. Five patients had the D48V mutation, 4 (patients 10, 11, 16, and 19) in homozygous state and 1 (patient 15) in compound heterozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26642834" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated children with MC2DN4, <a href="#4" class="mim-tip-reference" title="Gronborg, S., Darin, N., Miranda, M. J., Damgaard, B., Cayuela, J. A., Oldfors, A., Kollberg, G., Hansen, T. V. O., Ravn, K., Wibrand, F., Ostergaard, E. <strong>Leukoencephalopathy due to complex II deficiency and bi-allelic SDHB mutations: further cases and implications for genetic counselling.</strong> JIMD Rep. 33: 69-77, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27604842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27604842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27604842[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/10.1007/8904_2016_582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27604842">Gronborg et al. (2017)</a> identified mutations in the SDHB gene: a Lebanese girl, born of consanguineous parents, was homozygous for a missense mutation (L257V; <a href="/entry/185470#0022">185470.0022</a>), and a boy, born of nonconsanguineous parents, was compound heterozygous for D48V and another missense mutation (R230H; <a href="/entry/185470#0023">185470.0023</a>). In both patients, SDHB protein content was reduced in patient fibroblasts, muscle fibers showed diffuse and severe lack of SDH staining, and complex II enzyme activity was severely deficient in muscle. The parents of both children were confirmed to be mutation carriers. <a href="#4" class="mim-tip-reference" title="Gronborg, S., Darin, N., Miranda, M. J., Damgaard, B., Cayuela, J. A., Oldfors, A., Kollberg, G., Hansen, T. V. O., Ravn, K., Wibrand, F., Ostergaard, E. <strong>Leukoencephalopathy due to complex II deficiency and bi-allelic SDHB mutations: further cases and implications for genetic counselling.</strong> JIMD Rep. 33: 69-77, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27604842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27604842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27604842[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/10.1007/8904_2016_582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27604842">Gronborg et al. (2017)</a> noted that the R230H mutation was previously reported in heterozygous state in patients with paraganglioma by several authors, including <a href="#3" class="mim-tip-reference" title="Cerecer-Gil, N. Y., Figuera, L. E., Llamas, F. J., Lara, M., Escamilla, J. G., Ramos, R., Estrada, G., Karim Hussain, A., Gaal, J., Korpershoek, E., de Krijger, R. R., Dinjens, W. N. M., Devilee, P., Bayley, J. P. <strong>Mutation of SDHB is a cause of hypoxia-related high-altitude paraganglioma.</strong> Clin. Cancer Res. 16: 4148-4158, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20592014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20592014</a>] [<a href="https://doi.org/10.1158/1078-0432.CCR-10-0637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20592014">Cerecer-Gil et al. (2010)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20592014+27604842" 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 male infant with MC2DN4, who was born to nonconsanguineous Indian parents, <a href="#6" class="mim-tip-reference" title="Kaur, P., Sharma, S., Kadavigere, R., Girisha K. M., Shukla, A. <strong>Novel variant p.(Ala102Thr) in SDHB causes mitochondrial complex II deficiency: case report and review of the literature.</strong> Ann. Hum. Genet. 84: 345-351, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32124427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32124427</a>] [<a href="https://doi.org/10.1111/ahg.12377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32124427">Kaur et al. (2020)</a> identified a homozygous missense mutation in the SDHB gene (A102T; <a href="/entry/185470#0024">185470.0024</a>). The parents were heterozygous for the mutation. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32124427" 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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Alston, C. L., Davison, J. E., Meloni, F., van der Westhuizen, F. H., He, L., Hornig-Do, H.-T., Peet, A. C., Gissen, P., Goffrini, P., Ferrero, I., Wassmer, E., McFarland, R., Taylor, R. W.
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<strong>Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22972948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22972948</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22972948[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=22972948" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmedgenet-2012-101146" target="_blank">Full Text</a>]
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Ardissone, A., Invernizzi, F., Nasca, A., Moroni, I., Farina, L., Ghezzi, D.
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<strong>Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance.</strong>
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Molec. Genet. Metab. Rep. 5: 51-54, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26925370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26925370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26925370[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=26925370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgmr.2015.10.006" target="_blank">Full Text</a>]
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Cerecer-Gil, N. Y., Figuera, L. E., Llamas, F. J., Lara, M., Escamilla, J. G., Ramos, R., Estrada, G., Karim Hussain, A., Gaal, J., Korpershoek, E., de Krijger, R. R., Dinjens, W. N. M., Devilee, P., Bayley, J. P.
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<strong>Mutation of SDHB is a cause of hypoxia-related high-altitude paraganglioma.</strong>
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Clin. Cancer Res. 16: 4148-4158, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20592014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20592014</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20592014" 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/10.1158/1078-0432.CCR-10-0637" target="_blank">Full Text</a>]
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Gronborg, S., Darin, N., Miranda, M. J., Damgaard, B., Cayuela, J. A., Oldfors, A., Kollberg, G., Hansen, T. V. O., Ravn, K., Wibrand, F., Ostergaard, E.
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<strong>Leukoencephalopathy due to complex II deficiency and bi-allelic SDHB mutations: further cases and implications for genetic counselling.</strong>
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JIMD Rep. 33: 69-77, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27604842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27604842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27604842[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=27604842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Helman, G., Caldovic, L., Whitehead, M. T., Simons, C., Brockmann, K., Edvardson, S., Bai, R., Moroni, I., Taylor, J. M., Van Haren K., SDH Study Group, Taft, R. J., Vanderver, A., van der Knaap, M. S.
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<strong>Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy.</strong>
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Ann. Neurol. 79: 379-386, 2016. Note: Erratum: Ann. Neurol. 84: 481 only, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26642834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26642834</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26642834[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=26642834" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Kaur, P., Sharma, S., Kadavigere, R., Girisha K. M., Shukla, A.
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<strong>Novel variant p.(Ala102Thr) in SDHB causes mitochondrial complex II deficiency: case report and review of the literature.</strong>
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Ann. Hum. Genet. 84: 345-351, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32124427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32124427</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32124427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Vanderver, A., Simons, C., Helman, G., Crawford, J., Wolf, N. I., Bernard, G., Pizzino, A., Schmidt, J. L., Takanohashi, A., Miller, D., Khouzam, A., Rajan, V., and 17 others.
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<strong>Whole exome sequencing in patients with white matter abnormalities.</strong>
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Ann. Neurol. 79: 1031-1037, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27159321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27159321</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27159321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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carol : 02/16/2022<br>carol : 09/24/2021<br>carol : 03/10/2021<br>carol : 03/09/2021<br>carol : 03/08/2021
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MITOCHONDRIAL COMPLEX II DEFICIENCY, NUCLEAR TYPE 4; MC2DN4
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<strong>ORPHA:</strong> 3208;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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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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1p36.13
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Mitochondrial complex II deficiency, nuclear type 4
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619224
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Autosomal recessive
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3
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SDHB
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185470
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that mitochondrial complex II deficiency nuclear type 4 (MC2DN4) is caused by homozygous or compound heterozygous mutation in the succinate dehydrogenase complex subunit B gene (SDHB; 185470) on chromosome 1p36.</p>
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<strong>Description</strong>
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<p>Mitochondrial complex II deficiency nuclear type 4 (MC2DN4) is a severe autosomal recessive disorder characterized by early-onset progressive neurodegeneration with leukoencephalopathy. Acute episodes of neurodegeneration are often triggered by catabolic stress such as infection or fasting.</p>
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<strong>Clinical Features</strong>
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<p>Alston et al. (2012) reported an Asian girl, born of consanguineous parents, with neurologic impairment, leukoencephalopathy, and biochemical evidence of mitochondrial complex II deficiency. The patient showed developmental regression beginning at age 1 year. She was hypotonic with joint contractures, and she became wheelchair-bound at age 4 years. Brain MRI showed leukodystrophy in the deep white matter and signal abnormalities in the corpus callosum. MR spectroscopy showed increased lactate and increased succinate in the dystrophic white matter. </p><p>Ardissone et al. (2015) reported a Pakistani girl who presented at 15 months of age with acute psychomotor depression that developed several days after a febrile illness. On evaluation one month later, she had general hypotonia, hyperreflexia, lack of postural control, and irritability. Laboratory studies showed elevated plasma lactate and pyruvate and elevated 2-ketoglutarate in the urine. Brain MRI showed diffuse hyperintensity of the hemispheric white matter and corpus callosum with sparing of the subcortical U-fibers, hyperintensities of the bilateral thalami, and cystic degeneration of the deep white matter. HNMR-spectroscopy revealed succinate and lactate peaks. Visual evoked potential testing showed central conduction abnormalities. Her healthy 11-year-old sib had the same homozygous mutation in the SDHB gene (D48V; 185470.0020), leading Ardissone et al. (2015) to hypothesize that triggering stimuli may have been necessary to produce a clinical phenotype. </p><p>Vanderver et al. (2016) reported a Turkish boy (patient LD_0756.0A), born of consanguineous parents, who had motor delays from birth and acutely decompensated at 7 months of age. He had ataxia, hypotonia, and spasticity. Brain MRI at 3.5 years of age showed abnormal signal in the supratentorial white matter with sparing of the U-fibers, a swollen appearance of the corpus callosum, and involvement of the cerebellar white matter of the brainstem. </p><p>Helman et al. (2016) reported clinical and radiologic features in 5 patients, 4 of whom were living (patients 10, 11, 16 and 19) with an age range of 19 months to 9 years, and one of whom died at 1 year of age from respiratory failure (patient 15). Age of onset of symptoms ranged from birth to 18 months. In the 4 patients who had an MRI within the first 2 years of life, all had involvement of the corpus callosum and the thalamic nuclei, 3 had involvement of the middle cerebellar peduncles and pons, 3 had involvement of the spinal cord, 3 had involvement of the corticospinal tracts, and 2 had involvement of the cerebellar white matter. Patient 10 had spastic tetraparesis and normal cognition. Patient 11 had dilated cardiomyopathy with significant hypertrophy and poor function, gross motor impairment with contractures, and intact cognition. Patient 16 had spastic diplegia with severe motor difficulties and severe cognitive impairment. Patient 19 had generalized hypotonia, lack of postural control, irritability, and moderate cognitive impairment. </p><p>Gronborg et al. (2017) reported 2 unrelated patients with complex II deficiency. Patient 1, a Lebanese girl born to consanguineous parents, had slight developmental delay and hypotonia in the first year of life. She then had a progressive loss of developmental milestones starting at age 12 months, which was more pronounced during infections. At age 15 months, she had truncal hypotonia and increased muscle tone and increased reflexes in the limbs. She had slight bilateral optic atrophy, reduced vision, and horizontal nystagmus with opsoclonus. Brain MRI at age 16 months showed signal intensities in the frontal, parietooccipital, and posterior temporal white matter with sparing of the juxtacortical fibers. Laboratory studies showed an increased blood lactate and increased ketones and Krebs cycle intermediates (especially succinate) in the urine. She died at age 25 months of multiorgan failure in the setting of a respiratory infection. Patient 2, a boy born of nonconsanguineous parents, had intrauterine growth retardation, with decreased head circumference, length, and weight at birth. Starting at age 6 months, he had progressive loss of acquired skills, which was worse during infections. At age 9 months, he had pneumonia and respiratory failure necessitating assisted ventilation, and he had further loss of developmental skills. Laboratory studies showed increased blood lactate, increased ALAT and ASAT, increased creatine kinase, and increased INR. He had cardiomyopathy with severe dilatation and hypertrophy of the septum and posterior wall of the left ventricle. MRI at age 11 months showed signal intensities in the frontal, parietooccipital, and posterior temporal white matter with sparing of the juxtacortical fibers. He was stable with some improvement until 1 year of age when he died from multiorgan failure and cardiac arrest. </p><p>Kaur et al. (2020) reported an Indian boy who had regression of milestones at 1 year of age. He developed febrile seizures at age 18 months. On examination, he had increased tone in all limbs and brisk deep tendon reflexes. Ophthalmologic examination revealed bilateral optic atrophy. Brain MRI showed confluent lesions in the periventricular white matter, corpus callosum, dorsomedial thalami, brainstem, and spinal cord. Plasma and CSF lactate were elevated. </p>
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<h4>
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<strong>Inheritance</strong>
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<p>The transmission pattern of MC2DN4 in the patients reported by Alston et al. (2012) and Ardissone et al. (2015) was consistent with autosomal recessive inheritance. </p>
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<strong>Molecular Genetics</strong>
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<p>In an Asian girl, born of consanguineous parents, with neurologic impairment, leukoencephalopathy, and biochemical evidence of mitochondrial complex II deficiency, Alston et al. (2012) identified a homozygous missense mutation in the SDHB gene (D48V; 185470.0020). Her unaffected parents were heterozygous for the mutation. Patient fibroblasts showed decreased amounts of fully assembled complex II and almost complete absence of the SDHB subunit. Complex II activity was also decreased in patient muscle samples. </p><p>In a Pakistani girl, born to consanguineous parents, with MC2DN4, Ardissone et al. (2015) identified homozygosity for the previously reported D48V mutation in the SDHB gene. The mutation was found by sequencing of a panel of 7 genes associated with complex II deficiency. A clinically unaffected sib was also homozygous for the mutation. SDHB protein expression was reduced in patient fibroblasts and lymphocytes as well as in lymphocytes from the clinically unaffected sib. SDHA protein was also reduced in these cells, possibly due to instability of complex II assembly. </p><p>In a Turkish boy, born of consanguineous parents, with MC2DN4, Vanderver et al. (2016) identified homozygosity for the D48V mutation in the SDHB gene. </p><p>In 6 patients with MC2DN4, Helman et al. (2016) identified mutations in the SDHB gene. Five patients had the D48V mutation, 4 (patients 10, 11, 16, and 19) in homozygous state and 1 (patient 15) in compound heterozygous state. </p><p>In 2 unrelated children with MC2DN4, Gronborg et al. (2017) identified mutations in the SDHB gene: a Lebanese girl, born of consanguineous parents, was homozygous for a missense mutation (L257V; 185470.0022), and a boy, born of nonconsanguineous parents, was compound heterozygous for D48V and another missense mutation (R230H; 185470.0023). In both patients, SDHB protein content was reduced in patient fibroblasts, muscle fibers showed diffuse and severe lack of SDH staining, and complex II enzyme activity was severely deficient in muscle. The parents of both children were confirmed to be mutation carriers. Gronborg et al. (2017) noted that the R230H mutation was previously reported in heterozygous state in patients with paraganglioma by several authors, including Cerecer-Gil et al. (2010). </p><p>In a male infant with MC2DN4, who was born to nonconsanguineous Indian parents, Kaur et al. (2020) identified a homozygous missense mutation in the SDHB gene (A102T; 185470.0024). The parents were heterozygous for the mutation. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</h4>
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Alston, C. L., Davison, J. E., Meloni, F., van der Westhuizen, F. H., He, L., Hornig-Do, H.-T., Peet, A. C., Gissen, P., Goffrini, P., Ferrero, I., Wassmer, E., McFarland, R., Taylor, R. W.
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<strong>Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency.</strong>
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J. Med. Genet. 49: 569-577, 2012.
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[PubMed: 22972948]
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[Full Text: https://doi.org/10.1136/jmedgenet-2012-101146]
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Ardissone, A., Invernizzi, F., Nasca, A., Moroni, I., Farina, L., Ghezzi, D.
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<strong>Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance.</strong>
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Molec. Genet. Metab. Rep. 5: 51-54, 2015.
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[PubMed: 26925370]
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[Full Text: https://doi.org/10.1016/j.ymgmr.2015.10.006]
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Cerecer-Gil, N. Y., Figuera, L. E., Llamas, F. J., Lara, M., Escamilla, J. G., Ramos, R., Estrada, G., Karim Hussain, A., Gaal, J., Korpershoek, E., de Krijger, R. R., Dinjens, W. N. M., Devilee, P., Bayley, J. P.
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<strong>Mutation of SDHB is a cause of hypoxia-related high-altitude paraganglioma.</strong>
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Clin. Cancer Res. 16: 4148-4158, 2010.
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[PubMed: 20592014]
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[Full Text: https://doi.org/10.1158/1078-0432.CCR-10-0637]
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Gronborg, S., Darin, N., Miranda, M. J., Damgaard, B., Cayuela, J. A., Oldfors, A., Kollberg, G., Hansen, T. V. O., Ravn, K., Wibrand, F., Ostergaard, E.
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<strong>Leukoencephalopathy due to complex II deficiency and bi-allelic SDHB mutations: further cases and implications for genetic counselling.</strong>
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JIMD Rep. 33: 69-77, 2017.
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[PubMed: 27604842]
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[Full Text: https://doi.org/10.1007/8904_2016_582]
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Helman, G., Caldovic, L., Whitehead, M. T., Simons, C., Brockmann, K., Edvardson, S., Bai, R., Moroni, I., Taylor, J. M., Van Haren K., SDH Study Group, Taft, R. J., Vanderver, A., van der Knaap, M. S.
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<strong>Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy.</strong>
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Ann. Neurol. 79: 379-386, 2016. Note: Erratum: Ann. Neurol. 84: 481 only, 2018.
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[PubMed: 26642834]
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[Full Text: https://doi.org/10.1002/ana.24572]
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Kaur, P., Sharma, S., Kadavigere, R., Girisha K. M., Shukla, A.
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<strong>Novel variant p.(Ala102Thr) in SDHB causes mitochondrial complex II deficiency: case report and review of the literature.</strong>
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Ann. Hum. Genet. 84: 345-351, 2020.
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[PubMed: 32124427]
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[Full Text: https://doi.org/10.1111/ahg.12377]
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Vanderver, A., Simons, C., Helman, G., Crawford, J., Wolf, N. I., Bernard, G., Pizzino, A., Schmidt, J. L., Takanohashi, A., Miller, D., Khouzam, A., Rajan, V., and 17 others.
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<strong>Whole exome sequencing in patients with white matter abnormalities.</strong>
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Ann. Neurol. 79: 1031-1037, 2016.
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[PubMed: 27159321]
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[Full Text: https://doi.org/10.1002/ana.24650]
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Creation Date:
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Hilary J. Vernon : 03/05/2021
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Edit History:
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alopez : 11/28/2022<br>carol : 02/16/2022<br>carol : 09/24/2021<br>carol : 03/10/2021<br>carol : 03/09/2021<br>carol : 03/08/2021
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OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
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Thank you in advance for your generous support, <br />
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