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<title>
Entry
- #252010 - MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 1; MC1DN1
- OMIM
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<span class="h4">#252010</span>
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
<a href="/clinicalSynopsis/252010"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
<a href="/phenotypicSeries/PS252010"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#animalModel">Animal Model</a>
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<a href="#history">History</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<div style="display: table-row">
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">Clinical Resources</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
<div class="panel-body small mim-panel-body">
<div><a href="https://clinicaltrials.gov/search?cond=(MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE) OR (NDUFS4)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=369&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>
<div><a href="https://www.diseaseinfosearch.org/x/4823" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://medlineplus.gov/genetics/condition/mitochondrial-complex-i-deficiency" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=252010[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>
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2609" 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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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
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</a>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0112074" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/252010" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0112074" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:252010" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 237988006<br />
<strong>ORPHA:</strong> 2609<br />
<strong>DO:</strong> 0112074<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
252010
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 1; MC1DN1
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
MITOCHONDRIAL COMPLEX I DEFICIENCY<br />
NADH:Q(1) OXIDOREDUCTASE DEFICIENCY<br />
NADH-COENZYME Q REDUCTASE DEFICIENCY<br />
MITOCHONDRIAL NADH DEHYDROGENASE COMPONENT OF COMPLEX I, DEFICIENCY OF
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/159?start=-3&limit=10&highlight=159">
5q11.2
</a>
</span>
</td>
<td>
<span class="mim-font">
Mitochondrial complex I deficiency, nuclear type 1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252010"> 252010 </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">
NDUFS4
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602694"> 602694 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/252010" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS252010" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
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</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/252010" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/252010" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal 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 />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br /> -
Growth retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59576002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59576002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/444896005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">444896005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151686</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Microcephaly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sensorineural deafness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60700002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60700002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018784</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span><br /> -
Auditory neuropathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/443805006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">443805006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1852271&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1852271</a>, <a href="https://bioportal.bioontology.org/search?q=C2732267&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2732267</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Nystagmus <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 /> -
Pale optic disks <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302200001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302200001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0554970&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0554970</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000543</a>]</span><br /> -
Optic neuropathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/77157004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">77157004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029132&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029132</a>, <a href="https://bioportal.bioontology.org/search?q=C3887709&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887709</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001138" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001138</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001138" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001138</a>]</span><br /> -
Strabismus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22066006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22066006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038379</a>, <a href="https://bioportal.bioontology.org/search?q=C2020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2020541</a>, <a href="https://bioportal.bioontology.org/search?q=C1423541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1423541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span><br /> -
Ptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29696001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29696001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a>, <a href="https://bioportal.bioontology.org/search?q=C0033377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Blindness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0456909&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456909</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000618</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000618</a>]</span><br /> -
Abnormal eye movements <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103252009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103252009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0497202&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0497202</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000496" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000496</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000496" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000496</a>]</span><br /> -
Poor eye contact <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/412786000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">412786000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1445953&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1445953</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000817" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000817</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000817" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000817</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypertrophic cardiomyopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195020003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195020003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233873004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233873004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45227007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45227007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/425.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.11</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551472&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551472</a>, <a href="https://bioportal.bioontology.org/search?q=C0340425&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0340425</a>, <a href="https://bioportal.bioontology.org/search?q=C0007194&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007194</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Respiratory insufficiency <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>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409623005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409623005</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>, <a href="https://bioportal.bioontology.org/search?q=C0035229&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035229</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>, <a href="https://hpo.jax.org/app/browse/term/HP:0002093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002093</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002093</a>]</span><br /> -
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 />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Poor feeding <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299698007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299698007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0576456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576456</a>, <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br /> -
Vomiting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
Muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26544005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26544005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151786&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151786</a>, <a href="https://bioportal.bioontology.org/search?q=C0030552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030552</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Developmental delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
Psychomotor regression <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855019&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855019</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002376" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002376</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002376" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002376</a>]</span><br /> -
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
Poor head control <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002421" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002421</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002421" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002421</a>]</span><br /> -
Lethargy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/214264003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">214264003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span><br /> -
Hyporeflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700078</a>, <a href="https://bioportal.bioontology.org/search?q=C0151888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br /> -
Seizures <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 /> -
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 /> -
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 /> -
Acute necrotizing encephalopathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855020&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855020</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006965" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006965</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006965" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006965</a>]</span><br /> -
Leukodystrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/192781003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">192781003</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/330.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">330.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023520&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023520</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002415" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002415</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002415" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002415</a>]</span><br /> -
Cavitating leukoencephalopathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806435&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806435</a>]</span><br /> -
Abnormalities consistent with Leigh syndrome seen on brain imaging <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4746845&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4746845</a>]</span><br /> -
Brainstem lesions, hyperintense on T2-weighted imaging <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278493&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278493</a>]</span><br /> -
Striatal lesions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278494&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278494</a>]</span><br /> -
Thalamic lesions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278495&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278495</a>]</span><br /> -
Cerebellar lesions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0742035&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0742035</a>]</span><br /> -
Cerebellar atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740279</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Lactic acidosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91273001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91273001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0001125&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0001125</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span><br /> -
Hypoglycemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237630007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237630007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271327008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271327008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302866003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302866003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1179458001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1179458001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E16.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E16.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/251.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">251.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020615</a>, <a href="https://bioportal.bioontology.org/search?q=C5767385&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5767385</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001943</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001943</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Lactic acidemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/190882007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">190882007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0347959&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0347959</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span><br /> -
Increased CSF lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1167918&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1167918</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002490</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002490</a>]</span><br /> -
Decreased activity of mitochondrial respiratory chain complex I in various tissues <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4746846&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4746846</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br /> -
Variable phenotype <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837514</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br /> -
Early death may occur<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the NADH-ubiquinone oxidoreductase subunit S4 gene (NDUFS4, <a href="/entry/602694#0001">602694.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Mitochondrial complex I deficiency, nuclear type
- <a href="/phenotypicSeries/PS252010">PS252010</a>
- 39 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1344?start=-3&limit=10&highlight=1344"> 1q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618228"> Mitochondrial complex I deficiency, nuclear type 6 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618228"> 618228 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602985"> NDUFS2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602985"> 602985 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/911?start=-3&limit=10&highlight=911"> 2q33.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618246"> Mitochondrial complex I deficiency, nuclear type 25 </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/618246"> 618246 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603839"> NDUFB3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603839"> 603839 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/940?start=-3&limit=10&highlight=940"> 2q33.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618226"> Mitochondrial complex I deficiency, nuclear type 5 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618226"> 618226 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/157655"> NDUFS1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/157655"> 157655 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/1167?start=-3&limit=10&highlight=1167"> 2q37.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618243"> Mitochondrial complex I deficiency, nuclear type 22 </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/618243"> 618243 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603835"> NDUFA10 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603835"> 603835 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/297?start=-3&limit=10&highlight=297"> 3p21.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618240"> Mitochondrial complex I deficiency, nuclear type 18 </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/618240"> 618240 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612911"> NDUFAF3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612911"> 612911 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/573?start=-3&limit=10&highlight=573"> 3q13.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618251"> Mitochondrial complex I deficiency, nuclear type 31 </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/618251"> 618251 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615534"> TIMMDC1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615534"> 615534 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/655?start=-3&limit=10&highlight=655"> 3q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611126"> Mitochondrial complex I deficiency, nuclear type 20 </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/611126"> 611126 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611103"> ACAD9 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611103"> 611103 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/27?start=-3&limit=10&highlight=27"> 5p15.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618232"> Mitochondrial complex I deficiency, nuclear type 9 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618232"> 618232 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603848"> NDUFS6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603848"> 603848 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/159?start=-3&limit=10&highlight=159"> 5q11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252010"> Mitochondrial complex I deficiency, nuclear type 1 </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/252010"> 252010 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602694"> NDUFS4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602694"> 602694 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/194?start=-3&limit=10&highlight=194"> 5q12.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618233"> Mitochondrial complex I deficiency, nuclear type 10 </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/618233"> 618233 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609653"> NDUFAF2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609653"> 609653 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/540?start=-3&limit=10&highlight=540"> 5q31.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618235"> Mitochondrial complex I deficiency, nuclear type 13 </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/618235"> 618235 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602137"> NDUFA2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602137"> 602137 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/718?start=-3&limit=10&highlight=718"> 6q16.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618237"> Mitochondrial complex I deficiency, nuclear type 15 </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/618237"> 618237 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611776"> NDUFAF4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611776"> 611776 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/322?start=-3&limit=10&highlight=322"> 7q11.23 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619382"> Leber-like hereditary optic neuropathy, autosomal recessive 1 </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/619382"> 619382 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618202"> DNAJC30 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618202"> 618202 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/416?start=-3&limit=10&highlight=416"> 8q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618239"> Mitochondrial complex I deficiency, nuclear type 17 </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/618239"> 618239 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612392"> NDUFAF6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612392"> 612392 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/535?start=-3&limit=10&highlight=535"> 8q24.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618245"> ?Mitochondrial complex I deficiency, nuclear type 24 </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/618245"> 618245 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601445"> NDUFB9 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601445"> 601445 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/471?start=-3&limit=10&highlight=471"> 9q33.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619272"> Mitochondrial complex I deficiency, nuclear type 37 </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/619272"> 619272 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603359"> NDUFA8 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603359"> 603359 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/483?start=-3&limit=10&highlight=483"> 10q24.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618252"> Mitochondrial complex I deficiency, nuclear type 32 </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/618252"> 618252 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602140"> NDUFB8 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602140"> 602140 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/369?start=-3&limit=10&highlight=369"> 11p11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618230"> Mitochondrial complex I deficiency, nuclear type 8 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618230"> 618230 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603846"> NDUFS3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603846"> 603846 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/672?start=-3&limit=10&highlight=672"> 11q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618225"> Mitochondrial complex I deficiency, nuclear type 4 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618225"> 618225 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/161015"> NDUFV1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/161015"> 161015 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/678?start=-3&limit=10&highlight=678"> 11q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618222"> Mitochondrial complex I 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/618222"> 618222 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602141"> NDUFS8 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602141"> 602141 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/787?start=-3&limit=10&highlight=787"> 11q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619170"> Mitochondrial complex I deficiency, nuclear type 36 </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/619170"> 619170 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603845"> NDUFC2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603845"> 603845 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/802?start=-3&limit=10&highlight=802"> 11q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618250"> Mitochondrial complex I deficiency, nuclear type 29 </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/618250"> 618250 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615533"> TMEM126B </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615533"> 615533 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/1076?start=-3&limit=10&highlight=1076"> 11q24.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618241"> Mitochondrial complex I deficiency, nuclear type 19 </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/618241"> 618241 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613622"> FOXRED1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613622"> 613622 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/38?start=-3&limit=10&highlight=38"> 12p13.32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618247"> Mitochondrial complex I deficiency, nuclear type 26 </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/618247"> 618247 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603834"> NDUFA9 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603834"> 603834 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/694?start=-3&limit=10&highlight=694"> 12q22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618244"> Mitochondrial complex I deficiency, nuclear type 23 </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/618244"> 618244 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614530"> NDUFA12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614530"> 614530 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/14/154?start=-3&limit=10&highlight=154"> 14q12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618242"> Mitochondrial complex I deficiency, nuclear type 21 </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/618242"> 618242 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613621"> NUBPL </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613621"> 613621 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/118?start=-3&limit=10&highlight=118"> 15q15.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618234"> Mitochondrial complex I deficiency, nuclear type 11 </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/618234"> 618234 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606934"> NDUFAF1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606934"> 606934 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/290?start=-3&limit=10&highlight=290"> 15q22.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618248"> Mitochondrial complex I deficiency, nuclear type 27 </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/618248"> 618248 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611766"> MTFMT </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611766"> 611766 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/83?start=-3&limit=10&highlight=83"> 16p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619003"> ?Mitochondrial complex I deficiency, nuclear type 35 </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/619003"> 619003 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603843"> NDUFB10 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603843"> 603843 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/1028?start=-3&limit=10&highlight=1028"> 17q25.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618776"> Mitochondrial complex I deficiency, nuclear type 34 </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/618776"> 618776 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618461"> NDUFAF8 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618461"> 618461 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/18/46?start=-3&limit=10&highlight=46"> 18p11.22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618229"> Mitochondrial complex I deficiency, nuclear type 7 </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/618229"> 618229 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600532"> NDUFV2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600532"> 600532 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/51?start=-3&limit=10&highlight=51"> 19p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618224"> Mitochondrial complex I 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/618224"> 618224 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601825"> NDUFS7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601825"> 601825 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/168?start=-3&limit=10&highlight=168"> 19p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618236"> Mitochondrial complex I deficiency, nuclear type 14 </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/618236"> 618236 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612638"> NDUFA11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612638"> 612638 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/383?start=-3&limit=10&highlight=383"> 19p13.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620135"> ?Mitochondrial complex I deficiency, nuclear type 39 </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/620135"> 620135 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603842"> NDUFB7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603842"> 603842 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/493?start=-3&limit=10&highlight=493"> 19p13.11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618249"> Mitochondrial complex I deficiency, nuclear type 28 </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/618249"> 618249 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609435"> NDUFA13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609435"> 609435 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/20/105?start=-3&limit=10&highlight=105"> 20p12.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618238"> Mitochondrial complex I deficiency, nuclear type 16 </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/618238"> 618238 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612360"> NDUFAF5 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612360"> 612360 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/22/342?start=-3&limit=10&highlight=342"> 22q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618253"> Mitochondrial complex I deficiency, nuclear type 33 </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/618253"> 618253 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602138"> NDUFA6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602138"> 602138 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/209?start=-3&limit=10&highlight=209"> Xp11.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/301021"> ?Mitochondrial complex I deficiency, nuclear type 30 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked">XL</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/301021"> 301021 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300403"> NDUFB11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300403"> 300403 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/619?start=-3&limit=10&highlight=619"> Xq24 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/301020"> Mitochondrial complex I deficiency, nuclear type 12 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</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/301020"> 301020 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300078"> NDUFA1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300078"> 300078 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
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<div>
<br />
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<div>
<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 1 (MC1DN1) is caused by homozygous mutation in the NDUFS4 gene (<a href="/entry/602694">602694</a>) on chromosome 5q11.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="description" class="mim-anchor"></a>
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Description</strong>
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</h4>
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<span class="mim-text-font">
<p>Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (<a href="#21" class="mim-tip-reference" title="McFarland, R., Kirby, D. M., Fowler, K. J., Ohtake, A., Ryan, M. T., Amor, D. J., Fletcher, J. M., Dixon, J. W., Collins, F. A., Turnbull, D. M., Taylor, R. W., Thorburn, D. R. &lt;strong&gt;De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency.&lt;/strong&gt; Ann. Neurol. 55: 58-64, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14705112/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14705112&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.10787&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14705112">McFarland et al., 2004</a>; <a href="#16" class="mim-tip-reference" title="Kirby, D. M., Salemi, R., Sugiana, C., Ohtake, A., Parry, L., Bell, K. M., Kirk, E. P., Boneh, A., Taylor, R. W., Dahl, H.-H. M., Ryan, M. T., Thorburn, D. R. &lt;strong&gt;NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency.&lt;/strong&gt; J. Clin. Invest. 114: 837-845, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15372108/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15372108&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15372108[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI20683&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15372108">Kirby et al., 2004</a>). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (see <a href="/entry/256000">256000</a>), Leber hereditary optic neuropathy (<a href="/entry/535000">535000</a>), and some forms of Parkinson disease (see <a href="/entry/556500">556500</a>) (<a href="#19" class="mim-tip-reference" title="Loeffen, J. L. C. M., Smeitink, J. A. M., Trijbels, J. M. F., Janssen, A. J. M., Triepels, R. H., Sengers, R. C. A., van den Heuvel, L. P. &lt;strong&gt;Isolated complex I deficiency in children: clinical, biochemical and genetic aspects.&lt;/strong&gt; Hum. Mutat. 15: 123-134, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10649489/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10649489&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(200002)15:2&lt;123::AID-HUMU1&gt;3.0.CO;2-P&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10649489">Loeffen et al., 2000</a>; <a href="#26" class="mim-tip-reference" title="Pitkanen, S., Feigenbaum, A., Laframboise, R., Robinson, B. H. &lt;strong&gt;NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings.&lt;/strong&gt; J. Inherit. Metab. Dis. 19: 675-686, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8892026/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8892026&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799845&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8892026">Pitkanen et al., 1996</a>; <a href="#28" class="mim-tip-reference" title="Robinson, B. H. &lt;strong&gt;Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect.&lt;/strong&gt; Biochim. Biophys. Acta 1364: 271-286, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9593934/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9593934&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0005-2728(98)00033-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9593934">Robinson, 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15372108+8892026+10649489+14705112+9593934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity of Complex I Deficiency</em></strong></p><p>
Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible (summary by <a href="#14" class="mim-tip-reference" title="Haack, T. B., Haberberger, B., Frisch, E.-M., Wieland, T., Iuso, A., Gorza, M., Strecker, V., Graf, E., Mayr, J. A., Herberg, U., Hennermann, J. B., Klopstock, T., and 16 others. &lt;strong&gt;Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing.&lt;/strong&gt; J. Med. Genet. 49: 277-283, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22499348/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22499348&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmedgenet-2012-100846&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22499348">Haack et al., 2012</a>). However, the majority of cases are caused by mutations in nuclear-encoded genes (<a href="#19" class="mim-tip-reference" title="Loeffen, J. L. C. M., Smeitink, J. A. M., Trijbels, J. M. F., Janssen, A. J. M., Triepels, R. H., Sengers, R. C. A., van den Heuvel, L. P. &lt;strong&gt;Isolated complex I deficiency in children: clinical, biochemical and genetic aspects.&lt;/strong&gt; Hum. Mutat. 15: 123-134, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10649489/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10649489&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(200002)15:2&lt;123::AID-HUMU1&gt;3.0.CO;2-P&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10649489">Loeffen et al., 2000</a>; <a href="#33" class="mim-tip-reference" title="Triepels, R. H., van den Heuvel, L. P., Trijbels, J. M., Smeitink, J. A. &lt;strong&gt;Respiratory chain complex I deficiency.&lt;/strong&gt; Am. J. Med. Genet. 106: 37-45, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11579423/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11579423&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1397&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11579423">Triepels et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22499348+10649489+11579423" 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>Complex I deficiency resulting from mutation in nuclear-encoded genes include MC1DN1, caused by mutation in the NDUFS4 gene (<a href="/entry/602694">602694</a>); MC1DN2 (<a href="/entry/618222">618222</a>), caused by mutation in the NDUFS8 gene (<a href="/entry/602141">602141</a>); MC1DN3 (<a href="/entry/618224">618224</a>), caused by mutation in the NDUFS7 gene (<a href="/entry/601825">601825</a>); MC1DN4 (<a href="/entry/618225">618225</a>), caused by mutation in the NDUFV1 gene (<a href="/entry/161015">161015</a>); MC1DN5 (<a href="/entry/618226">618226</a>), caused by mutation in the NDUFS1 gene (<a href="/entry/157655">157655</a>); MC1DN6 (<a href="/entry/618228">618228</a>), caused by mutation in the NDUFS2 gene (<a href="/entry/602985">602985</a>); MC1DN7 (<a href="/entry/618229">618229</a>), caused by mutation in the NDUFV2 gene (<a href="/entry/600532">600532</a>); MC1DN8 (<a href="/entry/618230">618230</a>), caused by mutation in the NDUFS3 gene (<a href="/entry/603846">603846</a>); MC1DN9 (<a href="/entry/618232">618232</a>), caused by mutation in the NDUFS6 gene (<a href="/entry/603848">603848</a>); MC1DN10 (<a href="/entry/618233">618233</a>), caused by mutation in the NDUFAF2 gene (<a href="/entry/609653">609653</a>); MC1DN11 (<a href="/entry/618234">618234</a>), caused by mutation in the NDUFAF1 gene (<a href="/entry/606934">606934</a>); MC1DN12 (<a href="/entry/301020">301020</a>), caused by mutation in the NDUFA1 gene (<a href="/entry/300078">300078</a>); MC1DN13 (<a href="/entry/618235">618235</a>), caused by mutation in the NDUFA2 gene (<a href="/entry/602137">602137</a>); MC1DN14 (<a href="/entry/618236">618236</a>), caused by mutation in the NDUFA11 gene (<a href="/entry/612638">612638</a>); MC1DN15 (<a href="/entry/618237">618237</a>), caused by mutation in the NDUFAF4 gene (<a href="/entry/611776">611776</a>); MC1DN16 (<a href="/entry/618238">618238</a>), caused by mutation in the NDUFAF5 gene (<a href="/entry/612360">612360</a>); MC1DN17 (<a href="/entry/618239">618239</a>), caused by mutation in the NDUFAF6 gene (<a href="/entry/612392">612392</a>); MC1DN18 (<a href="/entry/618240">618240</a>), caused by mutation in the NDUFAF3 gene (<a href="/entry/612911">612911</a>); MC1DN19 (<a href="/entry/618241">618241</a>), caused by mutation in the FOXRED1 gene (<a href="/entry/613622">613622</a>); MC1DN20 (<a href="/entry/611126">611126</a>), caused by mutation in the ACAD9 gene (<a href="/entry/611103">611103</a>); MC1DN21 (<a href="/entry/618242">618242</a>), caused by mutation in the NUBPL gene (<a href="/entry/613621">613621</a>); MC1DN22 (<a href="/entry/618243">618243</a>), caused by mutation in the NDUFA10 gene (<a href="/entry/603835">603835</a>); MC1DN23 (<a href="/entry/618244">618244</a>), caused by mutation in the NDUFA12 gene (<a href="/entry/614530">614530</a>); MC1DN24 (<a href="/entry/618245">618245</a>), caused by mutation in the NDUFB9 gene (<a href="/entry/601445">601445</a>); MC1DN25 (<a href="/entry/618246">618246</a>), caused by mutation in the NDUFB3 gene (<a href="/entry/603839">603839</a>); MC1DN26 (<a href="/entry/618247">618247</a>), caused by mutation in the NDUFA9 gene (<a href="/entry/603834">603834</a>); MC1DN27 (<a href="/entry/618248">618248</a>), caused by mutation in the MTFMT gene (<a href="/entry/611766">611766</a>); MC1DN28 (<a href="/entry/618249">618249</a>), caused by mutation in the NDUFA13 gene (<a href="/entry/609435">609435</a>); MC1DN29 (<a href="/entry/618250">618250</a>), caused by mutation in the TMEM126B gene (<a href="/entry/615533">615533</a>); MC1DN30 (<a href="/entry/301021">301021</a>), caused by mutation in the NDUFB11 gene (<a href="/entry/300403">300403</a>); MC1DN31 (<a href="/entry/618251">618251</a>), caused by mutation in the TIMMDC1 gene (<a href="/entry/615534">615534</a>); MC1DN32 (<a href="/entry/618252">618252</a>), caused by mutation in the NDUFB8 gene (<a href="/entry/602140">602140</a>); MC1DN33 (<a href="/entry/618253">618253</a>), caused by mutation in the NDUFA6 gene (<a href="/entry/602138">602138</a>); MC1DN34 (<a href="/entry/618776">618776</a>), caused by mutation in the NDUFAF8 gene (<a href="/entry/618461">618461</a>); MC1DN35 (<a href="/entry/619003">619003</a>), caused by mutation in the NDUFB10 gene (<a href="/entry/603843">603843</a>); MC1DN36 (<a href="/entry/619170">619170</a>), caused by mutation in the NDUFC2 gene (<a href="/entry/603845">603845</a>); MC1DN37 (<a href="/entry/619272">619272</a>), caused by mutation in the NDUFA8 gene (<a href="/entry/603359">603359</a>); MC1DN38 (<a href="/entry/619382">619382</a>), caused by mutation in the DNAJC30 gene (<a href="/entry/618202">618202</a>); and MC1DN39 (<a href="/entry/620135">620135</a>), caused by mutation in the NDUFB7 gene (<a href="/entry/603842">603842</a>).</p><p>Complex I deficiency with mitochondrial inheritance has been associated with mutation in 6 mitochondrial-encoded components of complex I: MTND1 (<a href="/entry/516000">516000</a>), MTND2 (<a href="/entry/516001">516001</a>), MTND3 (<a href="/entry/516002">516002</a>), MTND4 (<a href="/entry/516003">516003</a>), MTND5 (<a href="/entry/516005">516005</a>), MTND6 (<a href="/entry/516006">516006</a>). Most of these patients have a phenotype of Leber hereditary optic neuropathy (LHON; <a href="/entry/535000">535000</a>) or Leigh syndrome. Features of complex I deficiency may also be caused by mutation in other mitochondrial genes, including MTTS2 (<a href="/entry/590085">590085</a>).</p>
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<p><a href="#34" class="mim-tip-reference" title="van den Heuvel, L., Ruitenbeek, W., Smeets, R., Gelman-Kohan, Z., Elpeleg, O., Loeffen, J., Trijbels, F., Mariman, E., de Bruijn, D., Smeitink, J. &lt;strong&gt;Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit.&lt;/strong&gt; Am. J. Hum. Genet. 62: 262-268, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9463323/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9463323&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301716&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9463323">Van den Heuvel et al. (1998)</a> reported a patient with fatal multisystemic complex I deficiency and homozygous mutation in the NDUFS4 gene. He had normal muscle morphology and a remarkably nonspecific fatally progressive course without increased lactate concentrations in body fluids. He presented at 8 months of age with severe vomiting, failure to thrive, and hypotonia. At the age of 13 months, he showed severe psychomotor retardation, convulsions, bradypnea, cyanosis, hypotonia, and depressed tendon reflexes. Cerebral MRI showed generalized brain atrophy and symmetric basal ganglia abnormalities. He died of cardiorespiratory failure at the age of 16 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Budde, S. M. S., van den Heuvel, L. P. W. J., Janssen, A. J., Smeets, R. J. P., Buskens, C. A. F., DeMeirleir, L., Van Coster, R., Baethmann, M., Voit, T., Trijbels, J. M. F., Smeitink, J. A. M. &lt;strong&gt;Combined enzymatic complex I and III deficiency associated with mutations in the nuclear encoded NDUFS4 gene.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 275: 63-68, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10944442/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10944442&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/bbrc.2000.3257&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10944442">Budde et al. (2000)</a> reported 2 unrelated patients, born to consanguineous parents, with complex I deficiency and decreased activity of complex III. The female patient showed, within 1 week of age, hypotonia, absent eye contact, lethargy, and failure to thrive. At 3 months of age, microcephaly was present and lactic acidemia with an increased lactate/pyruvate ratio was found. CT and MRI showed bilateral basal ganglia hypodensities. The child died at 3 months of age. Except for hypospadias noted at birth, the male patient appeared normal until the age of 7 weeks at which time muscular hypotonia and lack of visual and auditive attention were observed. At the age of 3 months he was found to have elevated lactate levels in the blood. Cranial MRI showed hyperintense signals resembling those found in Leigh syndrome (see <a href="/entry/256000">256000</a>). Cardiac ultrasound showed concentric hypertrophy of the left ventricle with hypercontractility. He died from cardiocirculatory insufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10944442" 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="#25" class="mim-tip-reference" title="Petruzzella, V., Vergari, R., Puzziferri, I., Boffoli, D., Lamantea, E., Zeviani, M., Papa, S. &lt;strong&gt;A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome.&lt;/strong&gt; Hum. Molec. Genet. 10: 529-535, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11181577/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11181577&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/10.5.529&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11181577">Petruzzella et al. (2001)</a> reported a girl who after birth showed failure to thrive, psychomotor delay, hypotonia, seizures, lactic acidosis, cardiomyopathy, and basal ganglia lesions on ultrasound. She died at 7 months of age from respiratory failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181577" 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="Benit, P., Steffann, J., Lebon, S., Chretien, D., Kadhom, N., de Lonlay, P., Goldenberg, A., Dumez, Y., Dommergues, M., Rustin, P., Munnich, A., Rotig, A. &lt;strong&gt;Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome.&lt;/strong&gt; Hum. Genet. 112: 563-566, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12616398/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12616398&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-002-0884-2&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12616398">Benit et al. (2003)</a> identified 2 sisters in a consanguineous family with complex I deficiency nuclear type 1 and Leigh syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12616398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Gonzalez-Quintana, A., Trujillo-Tiebas, M. J., Fernandez-Perrone, A. L., Blazquez, A., Lucia, A., Moran, M., Ugalde, C., Arenas, J., Ayuso, C., Martin, M. A. &lt;strong&gt;Uniparental isodisomy as a cause of mitochondrial complex I respiratory chain disorder due to a novel splicing NDUFS4 mutation.&lt;/strong&gt; Molec. Genet. Metab. 131: 341-348, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33093004/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33093004&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2020.10.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33093004">Gonzalez-Quintana et al. (2020)</a> reported a 7-year-old girl with a history of neonatal macrocephaly who presented with hypotonia, psychomotor delay, and exotropia at 6 months of age. Brain MRI at age 9 months showed abnormal signal in the vestibular nuclei and medial lemniscus, frontal bilateral polymicrogyria, and external hydrocephaly. At age 11 months, she had myoclonus of her arms. Laboratory studies showed lactic acidosis in serum and cerebral spinal fluid. Skeletal muscle biopsy showed type II fiber atrophy and an isolated defect of mitochondrial complex I activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33093004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Neuroradiologic Features in Patients with Known Nuclear or Mitochondrial Mutations</em></strong></p><p>
<a href="#18" class="mim-tip-reference" title="Lebre, A. S., Rio, M., Faivre d&#x27;Arcier, L., Vernerey, D., Landrieu, P., Slama, A., Jardel, C., Laforet, P., Rodriguez, D., Dorison, N., Galanaud, D., Chabrol, B., and 14 others. &lt;strong&gt;A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency.&lt;/strong&gt; J. Med. Genet. 48: 16-23, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20972245/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20972245&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2010.079624&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20972245">Lebre et al. (2011)</a> performed a retrospective review of the neuroradiologic features of 30 patients with complex I deficiency due to either nuclear (10 patients) or mitochondrial (20 patients) mutations. All patients had MRI abnormalities in the brainstem that were hyperintense on T2-weighted images and hypointense on T1-weighted images. Brainstem lesions were associated with at least 1 striatal anomaly (putamen or caudate) in 27 of 30 patients. Ten patients had thalamic anomalies, all of whom also had striatal lesions. Caudate lesions were more common in patients with mtDNA (50%) compared to those with nuclear (10%) mutations. Stroke-like lesions predominantly affecting the gray matter were observed in 40% of patients with mtDNA mutations, but in none of patients with nuclear mutations. A diffuse supratentorial leukoencephalopathy involving the deep lobar white matter was observed in over 50% of patients with nuclear mutations, but in none of patients with mtDNA mutations. Cerebellar hyperintensities were found in 45% of patients, regardless of the mutated genome, but cerebellar atrophy was found only in those with mtDNA mutations. All 10 patients studied had increased lactate on magnetic resonance spectroscopy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20972245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Patients with Unknown Mutations</em></strong></p><p>
<a href="#24" class="mim-tip-reference" title="Morgan-Hughes, J. A., Darveniza, P., Landon, D. N., Land, J. M., Clark, J. B. &lt;strong&gt;A mitochondrial myopathy with a deficiency of respiratory chain NADH-CoQ reductase activity.&lt;/strong&gt; J. Neurol. Sci. 43: 27-46, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/521828/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;521828&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(79)90071-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="521828">Morgan-Hughes et al. (1979)</a> presented the first report of isolated complex I deficiency. Two sisters had a mitochondrial myopathy characterized by weakness, marked exercise intolerance, and fluctuating lactic acidemia. Increased weakness was precipitated by unaccustomed exertion, fasting, or alcohol. During exercise, blood lactate and pyruvate levels rose abruptly and markedly. Mitochondrial respiratory rates were greatly decreased with all NAD-linked substrates, but normal with succinate and with TMPD plus ascorbate. Mitochondrial cytochrome components were normal. <a href="#24" class="mim-tip-reference" title="Morgan-Hughes, J. A., Darveniza, P., Landon, D. N., Land, J. M., Clark, J. B. &lt;strong&gt;A mitochondrial myopathy with a deficiency of respiratory chain NADH-CoQ reductase activity.&lt;/strong&gt; J. Neurol. Sci. 43: 27-46, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/521828/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;521828&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(79)90071-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="521828">Morgan-Hughes et al. (1979)</a> concluded that the defect was at the level of the NADH-CoQ reductase complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=521828" 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="#17" class="mim-tip-reference" title="Land, J. M., Morgan-Hughes, J. A., Clark, J. B. &lt;strong&gt;Mitochondrial myopathy: biochemical studies revealing a deficiency of NADH-cytochrome b reductase activity.&lt;/strong&gt; J. Neurol. Sci. 50: 1-13, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7229653/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7229653&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(81)90038-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7229653">Land et al. (1981)</a> reported a young man with weakness, exercise intolerance, muscle wasting, and exercise-induced lactic acidosis. Biochemical studies showed deficiency of NADH-cytochrome b reductase. The defect appeared to be situated between NADH dehydrogenase and the CoQ-cytochrome b complex. <a href="#17" class="mim-tip-reference" title="Land, J. M., Morgan-Hughes, J. A., Clark, J. B. &lt;strong&gt;Mitochondrial myopathy: biochemical studies revealing a deficiency of NADH-cytochrome b reductase activity.&lt;/strong&gt; J. Neurol. Sci. 50: 1-13, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7229653/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7229653&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(81)90038-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7229653">Land et al. (1981)</a> postulated a derangement of a nonheme iron-sulfur center. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7229653" 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="#22" class="mim-tip-reference" title="Moreadith, R. W., Batshaw, M. L., Ohnishi, T., Kerr, D., Knox, B., Jackson, D., Hruban, R., Olson, J., Reynafarje, B., Lehninger, A. L. &lt;strong&gt;Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.&lt;/strong&gt; J. Clin. Invest. 74: 685-697, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6432847/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6432847&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI111484&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6432847">Moreadith et al. (1984)</a> reported a male infant with complex I deficiency who developed respiratory distress and hypoglycemia on the first day of life. At 6 weeks, he showed generalized hypotonia and concentric biventricular cardiac hypertrophy on echocardiography. Lactic acidemia was progressive, and the child died at 16 weeks of age. Skeletal muscle biopsy showed giant mitochondria in which both inner and outer membranes were arranged in whorls. Biochemical studies of mitochondria from 4 organs showed a moderate to profound decrease in the ability to oxidize pyruvate, malate plus glutamate, citrate and other NAD-linked respiratory substrates. Oxidation of succinate was normal. Further studies localized the defect to the inner membrane mitochondrial NADH-ubiquinone oxidoreductase. Electron paramagnetic resonance spectroscopy showed almost total loss of the iron-sulfur clusters of complex I. The most pronounced deficiency was in skeletal muscle, the least in kidney mitochondria. There was no record of a similar problem in the family and the parents were not related. Since the parents subsequently had a normal male child, <a href="#22" class="mim-tip-reference" title="Moreadith, R. W., Batshaw, M. L., Ohnishi, T., Kerr, D., Knox, B., Jackson, D., Hruban, R., Olson, J., Reynafarje, B., Lehninger, A. L. &lt;strong&gt;Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.&lt;/strong&gt; J. Clin. Invest. 74: 685-697, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6432847/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6432847&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI111484&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6432847">Moreadith et al. (1984)</a> excluded mitochondrial inheritance and suggested either autosomal recessive inheritance or a de novo dominant mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6432847" 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 study on tissue from the patient reported by <a href="#22" class="mim-tip-reference" title="Moreadith, R. W., Batshaw, M. L., Ohnishi, T., Kerr, D., Knox, B., Jackson, D., Hruban, R., Olson, J., Reynafarje, B., Lehninger, A. L. &lt;strong&gt;Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.&lt;/strong&gt; J. Clin. Invest. 74: 685-697, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6432847/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6432847&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI111484&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6432847">Moreadith et al. (1984)</a>, <a href="#23" class="mim-tip-reference" title="Moreadith, R. W., Cleeter, M. W. J., Ragan, C. I., Batshaw, M. L., Lehninger, A. L. &lt;strong&gt;Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I.&lt;/strong&gt; J. Clin. Invest. 79: 463-467, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3100577/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3100577&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI112834&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3100577">Moreadith et al. (1987)</a> found that antisera against complex I immunoprecipitated NADH-ferricyanide reductase from the control but not the patient's mitochondria. Immunoprecipitation and SDS-PAGE of complex I polypeptides demonstrated that most of the 25 polypeptides comprising complex I were present in the affected mitochondria. A more detailed analysis using subunit selective antisera against the main polypeptides of the iron-protein fragments of complex I showed a selective absence of the 75- and 13-kD polypeptides, suggesting a deficiency of at least 2 polypeptides comprising the iron-protein fragment of complex I. <a href="#23" class="mim-tip-reference" title="Moreadith, R. W., Cleeter, M. W. J., Ragan, C. I., Batshaw, M. L., Lehninger, A. L. &lt;strong&gt;Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I.&lt;/strong&gt; J. Clin. Invest. 79: 463-467, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3100577/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3100577&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI112834&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3100577">Moreadith et al. (1987)</a> hypothesized that the genetic defect involved transcription or translation of the polypeptides, the transport of these polypeptides into the mitochondria, or the site of assembly of complex I. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3100577+6432847" 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="#15" class="mim-tip-reference" title="Hoppel, C. L., Kerr, D. S., Dahms, B., Roessmann, U. &lt;strong&gt;Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport: fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy.&lt;/strong&gt; J. Clin. Invest. 80: 71-77, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3110216/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3110216&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI113066&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3110216">Hoppel et al. (1987)</a> investigated a mitochondrial defect in a male infant with fatal congenital lactic acidosis, high lactate-to-pyruvate ratio, hypotonia, and cardiomyopathy. His sister had died with a similar disorder. Resting oxygen consumption was 150% of controls. Pathologic findings included increased numbers of skeletal muscle mitochondria (many with proliferated, concentric cristae), cardiomegaly, fatty infiltration of the viscera, and spongy encephalopathy. Mitochondria from liver and muscle biopsies oxidized NADH-linked substrates at rates 20 to 50% of controls, whereas succinate oxidation by muscle mitochondria was increased. Mitochondrial NADH dehydrogenase activity (complex I) was 0 to 10% of controls, whereas activity of other electron transport complexes in related enzymes was normal. <a href="#15" class="mim-tip-reference" title="Hoppel, C. L., Kerr, D. S., Dahms, B., Roessmann, U. &lt;strong&gt;Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport: fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy.&lt;/strong&gt; J. Clin. Invest. 80: 71-77, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3110216/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3110216&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI113066&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3110216">Hoppel et al. (1987)</a> suggested a familial deficiency of a component of mitochondrial NADH dehydrogenase proximal to the rotenone-sensitive site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3110216" 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="#37" class="mim-tip-reference" title="Wijburg, F. A., Barth, P. G., Ruitenbeek, W., Wanders, R. J. A., Vos, G. D., Ploos van Amstel, S. L. B., Schutgens, R. B. H. &lt;strong&gt;Familial NADH:Q(1) oxidoreductase (complex I) deficiency: variable expression and possible treatment.&lt;/strong&gt; J. Inherit. Metab. Dis. 12 (suppl. 2): 349-351, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2512441/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2512441&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF03335419&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2512441">Wijburg et al. (1989)</a> reported a sibship born to healthy first-cousin Moroccan parents with 2 well-studied children with severe congenital lactic acidosis as well as 4 others with a clinical history compatible with the same defect. Treatment initially by artificial respiration and peritoneal dialysis followed later by high doses of menadione effected a remarkable recovery. Despite the parental consanguinity, <a href="#3" class="mim-tip-reference" title="Barth, P. G., Bolhuis, P. A., Wijburg, F. A., Sinjorgo, K. M. C., Ruitenbeek, W., Schutgens, R. B. H. &lt;strong&gt;Familial mitochondrial complex I deficiency with an abnormal mitochondrial encoded protein.&lt;/strong&gt; J. Inherit. Metab. Dis. 12 (suppl. 2): 355-357, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2512443/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2512443&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF03335421&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2512443">Barth et al. (1989)</a> suggested that the defect in this family involved the mitochondrial genome: they detected a possible deletion in the mitochondrial-encoded MTND3 protein in skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2512443+2512441" 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="#29" class="mim-tip-reference" title="Slipetz, D. M., Goodyer, P. R., Rozen, R. &lt;strong&gt;Congenital deficiency of a 20-kDA subunit of mitochondrial complex I in fibroblasts.&lt;/strong&gt; Am. J. Hum. Genet. 48: 1121-1126, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1903590/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1903590&lt;/a&gt;]" pmid="1903590">Slipetz et al. (1991)</a> studied 2 unrelated patients with complex I deficiency with different phenotypes. One patient had hypotonia, seizures, and hepatomegaly, and died of lactic acidosis on day 13 of life. Biochemical analysis of complex I subunits showed absence of a 20-kD protein predicted to be encoded by the nuclear genome. Complex I activity was 6% of control values. The other child had marked growth and developmental delay, and showed altered neurologic function and seizures beginning at age 8 years. Other features included ptosis, sensorineural hearing loss, hypotonia, incoordination, and hyporeflexia. Mild facial coarseness was also observed. No complex I subunit abnormalities were detected by immunoprecipitation or Western blot analysis, but complex I activity was 15% of control values. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1903590" 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="Bentlage, H., de Coo, R., ter Laak, H., Sengers, R., Trijbels, F., Ruitenbeek, W., Schlote, W., Pfeiffer, K., Gencic, S., Von Jagow, G. &lt;strong&gt;Human diseases with defects in oxidative phosphorylation. I. Decreased amounts of assembled oxidative phosphorylation complexes in mitochondrial encephalomyopathies.&lt;/strong&gt; Europ. J. Biochem. 227: 909-915, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7867654/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7867654&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1432-1033.1995.tb20218.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7867654">Bentlage et al. (1995)</a> showed deficits of specific complex I protein subunits in patients with complex I deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7867654" 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="#11" class="mim-tip-reference" title="Dionisi-Vici, C., Ruitenbeek, W., Fariello, G., Bentlage, H., Wanders, R. J., Schagger, H., Bosman, C., Piantadosi, C., Sabetta, G., Bertini, E. &lt;strong&gt;New familial mitochondrial encephalopathy with macrocephaly, cardiomyopathy, and complex I deficiency.&lt;/strong&gt; Ann. Neurol. 42: 661-665, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9382480/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9382480&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410420419&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9382480">Dionisi-Vici et al. (1997)</a> reported 2 infant sibs with fatal progressive macrocephaly and hypertrophic cardiomyopathy. Onset of symptoms was at the end of the first month of life with massive brain swelling. Light microscopy showed extensive small-vessel proliferation and gliosis. Complex I deficiency was detected in cultured fibroblasts, skeletal muscle, and heart muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9382480" 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="#27" class="mim-tip-reference" title="Procaccio, V., Mousson, B., Beugnot, R., Duborjal, H., Feillet, F., Putet, G., Pignot-Paintrand, I., Lombes, A., De Coo, R., Smeets, H., Lunardi, J., Issartel, J.-P. &lt;strong&gt;Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts.&lt;/strong&gt; J. Clin. Invest. 104: 83-92, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10393702/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10393702&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10393702[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI6184&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10393702">Procaccio et al. (1999)</a> reported 2 unrelated patients with fatal infantile lactic acidosis associated with isolated complex I deficiency. Reexpression of complex I subunits and recovery of complex I activity in patients' mitochondria after transnuclear complementation by nuclei from cells without mitochondria enabled the authors to infer the nuclear DNA origin of the defects in both patients. Patient 1 showed reduced amounts of the 24- and 51-kD subunits and normal amounts of all the other investigated subunits. Patient 2 showed severely decreased amounts of all the investigated subunits. Patient 1 developed generalized hypotonia with poor gesticulation in the first 24 hours of life. By day 2, he was very floppy with poor response to painful stimuli and required ventilatory assistance. Hepatic enlargement was noticed, and chest x-rays showed slight cardiomegaly. Cranial ultrasonography showed brain edema, and severe lactic acidosis was detected. The patient went into a deep coma and died at 11 days. Patient 2 vomited frequently in the first 2 weeks of life and at 5 weeks showed deterioration of neurologic status with hypotonia, weakness, and lethargy. In the first month, the head circumference was noted to be rapidly increasing from 33 to 40 cm. Computed tomographic scan showed a very hypodense brain with increased brain volume and extensive cerebral edema. Marked metabolic acidosis with hyperlactic acidemia was demonstrated. Despite intensive care, the neurologic state worsened rapidly and brain death occurred at 6 weeks of age. Autopsy showed acute necrotizing encephalopathy, but no hypertrophic cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10393702" 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 study of 157 patients with respiratory chain defects, <a href="#35" class="mim-tip-reference" title="von Kleist-Retzow, J.-C., Cormier-Daire, V., de Lonlay, P., Parfait, B., Chretien, D., Rustin, P., Feingold, J., Rotig, A., Munnich, A. &lt;strong&gt;A high rate (20%-30%) of parental consanguinity in cytochrome-oxidase deficiency.&lt;/strong&gt; Am. J. Hum. Genet. 63: 428-435, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9683589/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9683589&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301957&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9683589">von Kleist-Retzow et al. (1998)</a> found complex I deficiency in 33% and combined complex I and IV deficiency in another 28%. The main clinical features in this series were truncal hypotonia (36%), antenatal (20%) and postnatal (31%) growth retardation, cardiomyopathy (24%), encephalopathy (20%), and liver failure (20%). No correlation was found between the type of respiratory chain defect and the clinical presentation, but complex I and complex I+IV deficiencies were significantly more frequent in cases of cardiomyopathy (p less than 0.01) and hepatic failure (p less than 0.05), respectively. The sex ratio was skewed toward males being affected with complex I deficiency. A high rate of parental consanguinity was observed in complex IV (20%) and complex I+IV (28%) deficiencies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683589" 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="#19" class="mim-tip-reference" title="Loeffen, J. L. C. M., Smeitink, J. A. M., Trijbels, J. M. F., Janssen, A. J. M., Triepels, R. H., Sengers, R. C. A., van den Heuvel, L. P. &lt;strong&gt;Isolated complex I deficiency in children: clinical, biochemical and genetic aspects.&lt;/strong&gt; Hum. Mutat. 15: 123-134, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10649489/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10649489&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(200002)15:2&lt;123::AID-HUMU1&gt;3.0.CO;2-P&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10649489">Loeffen et al. (2000)</a> retrospectively examined clinical and biochemical characteristics of 27 patients, all of whom presented in infancy and young childhood with isolated enzymatic complex I deficiency established in cultured skin fibroblasts; common pathogenic mtDNA point mutations and major rearrangements were absent. Clinical phenotypes included Leigh syndrome in 7 patients, Leigh-like syndrome in 6, fatal infantile lactic acidosis in 3, neonatal cardiomyopathy with lactic acidosis in 3, macrocephaly with progressive leukodystrophy in 2, and a residual group of unspecified encephalomyopathy in 6, subdivided into progressive (in 4) and stable (in 2) variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10649489" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="inheritance" class="mim-anchor"></a>
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<p>The transmission pattern of MC1DN1 in the patient reported by <a href="#34" class="mim-tip-reference" title="van den Heuvel, L., Ruitenbeek, W., Smeets, R., Gelman-Kohan, Z., Elpeleg, O., Loeffen, J., Trijbels, F., Mariman, E., de Bruijn, D., Smeitink, J. &lt;strong&gt;Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit.&lt;/strong&gt; Am. J. Hum. Genet. 62: 262-268, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9463323/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9463323&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301716&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9463323">van den Heuvel et al. (1998)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<p>In 1 of 20 patients with complex I deficiency nuclear type 1, <a href="#34" class="mim-tip-reference" title="van den Heuvel, L., Ruitenbeek, W., Smeets, R., Gelman-Kohan, Z., Elpeleg, O., Loeffen, J., Trijbels, F., Mariman, E., de Bruijn, D., Smeitink, J. &lt;strong&gt;Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit.&lt;/strong&gt; Am. J. Hum. Genet. 62: 262-268, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9463323/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9463323&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301716&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9463323">van den Heuvel et al. (1998)</a> identified a homozygous 5-bp duplication in the NDUFS4 gene (<a href="/entry/602694#0001">602694.0001</a>). The parents were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463323" 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 patients with complex I deficiency nuclear type 1 and decreased activity of complex III, <a href="#8" class="mim-tip-reference" title="Budde, S. M. S., van den Heuvel, L. P. W. J., Janssen, A. J., Smeets, R. J. P., Buskens, C. A. F., DeMeirleir, L., Van Coster, R., Baethmann, M., Voit, T., Trijbels, J. M. F., Smeitink, J. A. M. &lt;strong&gt;Combined enzymatic complex I and III deficiency associated with mutations in the nuclear encoded NDUFS4 gene.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 275: 63-68, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10944442/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10944442&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/bbrc.2000.3257&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10944442">Budde et al. (2000)</a> demonstrated homozygous mutations in the NDUFS4 gene (<a href="/entry/602694#0002">602694.0002</a> and <a href="/entry/602694#0003">602694.0003</a>). The mutations segregated with the disorder in both families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10944442" 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 patient with complex I deficiency presenting as Leigh syndrome, <a href="#25" class="mim-tip-reference" title="Petruzzella, V., Vergari, R., Puzziferri, I., Boffoli, D., Lamantea, E., Zeviani, M., Papa, S. &lt;strong&gt;A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome.&lt;/strong&gt; Hum. Molec. Genet. 10: 529-535, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11181577/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11181577&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/10.5.529&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11181577">Petruzzella et al. (2001)</a> identified a homozygous nonsense mutation in the NDUFS4 cDNA (W15X; <a href="/entry/602694#0004">602694.0004</a>). Both parents were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181577" 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 sisters in a consanguineous family with complex I deficiency and Leigh syndrome, <a href="#5" class="mim-tip-reference" title="Benit, P., Steffann, J., Lebon, S., Chretien, D., Kadhom, N., de Lonlay, P., Goldenberg, A., Dumez, Y., Dommergues, M., Rustin, P., Munnich, A., Rotig, A. &lt;strong&gt;Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome.&lt;/strong&gt; Hum. Genet. 112: 563-566, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12616398/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12616398&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-002-0884-2&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12616398">Benit et al. (2003)</a> identified a homozygous splice site mutation in the NDUFS4 locus (<a href="/entry/602694#0005">602694.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12616398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 sibs, born of Ashkenazi Jewish parents, with complex I deficiency nuclear type 1 manifesting as Leigh syndrome, <a href="#1" class="mim-tip-reference" title="Anderson, S. L., Chung, W. K., Frezzo, J., Papp, J. C., Ekstein, J., DiMauro, S., Rubin, B. Y. &lt;strong&gt;A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family.&lt;/strong&gt; J. Inherit. Metab. Dis. 31: S461-S467, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19107570/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19107570&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10545-008-1049-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19107570">Anderson et al. (2008)</a> identified a homozygous 1-bp deletion (462delA; <a href="/entry/602694#0006">602694.0006</a>) in the NDUFS4 gene. The mutation was identified by linkage analysis followed by candidate gene sequencing. Each unaffected parent and an unaffected sib were heterozygous for the mutation. The carrier frequency of the mutation, ascertained from 5,000 controls of Ashkenazi Jewish descent, was found to be 1 in 1,000, consistent with a founder effect in this population. Based on the results, <a href="#1" class="mim-tip-reference" title="Anderson, S. L., Chung, W. K., Frezzo, J., Papp, J. C., Ekstein, J., DiMauro, S., Rubin, B. Y. &lt;strong&gt;A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family.&lt;/strong&gt; J. Inherit. Metab. Dis. 31: S461-S467, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19107570/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19107570&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10545-008-1049-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19107570">Anderson et al. (2008)</a> used prenatal testing in this family to help the parents produce an unaffected child. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19107570" 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="Assereto, S., Robbiano, A., Di Rocco, M., Rossi, A., Cassandrini, D., Panicucci, C., Brigati, G., Biancheri, R., Bruno, C., Minetti, C., Trucks, H., Sander, T., Zara, F., Gazzerro, E. &lt;strong&gt;Functional characterization of the c.462delA mutation in the NDUFS4 subunit gene of mitochondrial complex I. (Letter)&lt;/strong&gt; Clin. Genet. 86: 99-101, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24020637/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24020637&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/cge.12248&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24020637">Assereto et al. (2014)</a> identified homozygosity for the 462delA mutation in the NDUFS4 gene in 2 sibs with mitochondrial complex I deficiency who were not of Ashkenazi Jewish descent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24020637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Gonzalez-Quintana, A., Trujillo-Tiebas, M. J., Fernandez-Perrone, A. L., Blazquez, A., Lucia, A., Moran, M., Ugalde, C., Arenas, J., Ayuso, C., Martin, M. A. &lt;strong&gt;Uniparental isodisomy as a cause of mitochondrial complex I respiratory chain disorder due to a novel splicing NDUFS4 mutation.&lt;/strong&gt; Molec. Genet. Metab. 131: 341-348, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33093004/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33093004&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2020.10.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33093004">Gonzalez-Quintana et al. (2020)</a> identified homozygosity for a splicing mutation (<a href="/entry/602694#0007">602694.0007</a>) in the NDUFS4 gene in a 7-year-old girl with MC1DN1. The patient's father carried the mutation, but her mother did not. Short tandem repeat analysis of DNA from the patient and her parents showed that homozygosity was caused by paternal uniparental disomy. Analysis of muscle and fibroblast cDNA from the patient showed reduced expression of NDUFS4, and several abnormal NDUFS4 transcripts were identified in the patient's muscle, indicative of abnormal splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33093004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>Mutations in the nuclear-encoded genes NDUFS1, NDUFS4, NDUFS7, NDUFS8, and NDUFV1 result in neurologic diseases, mostly Leigh syndrome or Leigh-like syndrome. Mutations in NDUFS2 and NDUFV2 have been associated with hypertrophic cardiomyopathy and encephalomyopathy. Mutations in the mitochondrial-encoded genes are associated with a wide variety of clinical symptoms, ranging from organ-specific to multisystem diseases (<a href="#4" class="mim-tip-reference" title="Benit, P., Slama, A., Cartault, F., Giurgea, I., Chretien, D., Lebon, S., Marsac, C., Munnich, A., Rotig, A., Rustin, P. &lt;strong&gt;Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome.&lt;/strong&gt; J. Med. Genet. 41: 14-17, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14729820/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14729820&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2003.014316&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14729820">Benit et al., 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14729820" 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="#32" class="mim-tip-reference" title="Swalwell, H., Kirby, D. M., Blakely, E. L., Mitchell, A., Salemi, R., Sugiana, C., Compton, A. G., Tucker, E. J., Ke, B.-X., Lamont, P. J., Turnbull, D. M., McFarland, R., Taylor, R. W., Thorburn, D. R. &lt;strong&gt;Respiratory chain complex I deficiency caused by mitochondrial DNA mutations.&lt;/strong&gt; Europ. J. Hum. Genet. 19: 769-775, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21364701/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21364701&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2011.18&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21364701">Swalwell et al. (2011)</a> reviewed the clinical and genetic findings in a large cohort of 109 pediatric patients with isolated complex I deficiency from 101 families. Pathogenic mtDNA mutations were found in 29% of probands: 21 in MTND subunit genes and 8 in mtDNA tRNA genes. Nuclear gene defects were inferred in 38% of probands based on cell hybrid studies, mtDNA sequencing, or mutation analysis. The most common clinical presentation was Leigh or Leigh-like disease in patients with either mtDNA or nuclear genetic defects. The median age at onset was later in mtDNA patients (12 months) compared to patients with a nuclear gene defect (3 months), although there was considerable overlap. The report confirmed that pathogenic mtDNA mutations are a significant cause of complex I deficiency in children. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21364701" 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 laboratory of Scheffler (<a href="#10" class="mim-tip-reference" title="DeFrancesco, L., Scheffler, I. E., Bissell, M. J. &lt;strong&gt;A respiration-deficient Chinese hamster cell line with a defect in NADH-coenzyme Q reductase.&lt;/strong&gt; J. Biol. Chem. 251: 4588-4595, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/947896/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;947896&lt;/a&gt;]" pmid="947896">DeFrancesco et al., 1976</a>; <a href="#12" class="mim-tip-reference" title="Ditta, G., Soderberg, K., Landy, F., Scheffler, I. E. &lt;strong&gt;The selection of Chinese hamster cells deficient in oxidative energy metabolism.&lt;/strong&gt; Somat. Cell Genet. 2: 331-344, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1027147/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1027147&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01538838&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1027147">Ditta et al., 1976</a>; <a href="#7" class="mim-tip-reference" title="Breen, G. A. M., Scheffler, I. E. &lt;strong&gt;Respiration-deficient Chinese hamster cell mutants: biochemical characterization.&lt;/strong&gt; Somat. Cell Genet. 5: 441-451, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/494059/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;494059&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01538879&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="494059">Breen and Scheffler, 1979</a>; <a href="#31" class="mim-tip-reference" title="Soderberg, K., Mascarello, J. T., Bakay, B., Scheffler, I. E. &lt;strong&gt;Respiration-deficient Chinese hamster cell mutants: genetic characterization.&lt;/strong&gt; Somat. Cell Genet. 5: 225-240, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/483122/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;483122&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01539163&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="483122">Soderberg et al., 1979</a>) described several respiration-deficient mutants of Chinese hamster cells in culture. All depended on an ample supply of glucose in the medium to sustain a high rate of glycolysis. When galactose was substituted for glucose, the mutants died. This property was used to sort about 3 dozen mutants into 7 complementation groups (<a href="#31" class="mim-tip-reference" title="Soderberg, K., Mascarello, J. T., Bakay, B., Scheffler, I. E. &lt;strong&gt;Respiration-deficient Chinese hamster cell mutants: genetic characterization.&lt;/strong&gt; Somat. Cell Genet. 5: 225-240, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/483122/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;483122&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01539163&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="483122">Soderberg et al., 1979</a>). <a href="#36" class="mim-tip-reference" title="Whitfield, C. D., Bostedor, P., Goodman, D., Haak, M., Chu, E. H. Y. &lt;strong&gt;Increased hexose transport in Chinese hamster ovary cells resistant to 3-O-methyl-D-glucose.&lt;/strong&gt; J. Biol. Chem. 256: 6651-6656, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7240234/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7240234&lt;/a&gt;]" pmid="7240234">Whitfield et al. (1981)</a> and <a href="#20" class="mim-tip-reference" title="Maiti, I. B., Comlan de Souza, A., Thirion, J. P. &lt;strong&gt;Biochemical and genetic characterization of respiration-deficient mutants of Chinese hamster cells with a Gal-phenotype.&lt;/strong&gt; Somat. Cell Genet. 7: 567-582, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7292258/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7292258&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01549659&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7292258">Maiti et al. (1981)</a> also identified gal-minus mutants in Chinese hamster cells that had a defect in the electron-transport chain. Specifically, several of the complementation groups appeared to be defective in complex I of the electron transport chain. <a href="#9" class="mim-tip-reference" title="Day, C. E., Scheffler, I. E. &lt;strong&gt;Mapping of the genes of some components of the electron transport chain (complex I) on the X chromosome of mammals.&lt;/strong&gt; Somat. Cell Genet. 8: 691-707, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6819642/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6819642&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01543012&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6819642">Day and Scheffler (1982)</a> reported that some of these complementation groups were X-linked in the hamster and mouse. The gene locus (-i) was symbolized 'res.' At least one complementation group was found to be autosomal. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7292258+947896+1027147+6819642+483122+7240234+494059" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="history" class="mim-anchor"></a>
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>History</strong>
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<p><a href="#17" class="mim-tip-reference" title="Land, J. M., Morgan-Hughes, J. A., Clark, J. B. &lt;strong&gt;Mitochondrial myopathy: biochemical studies revealing a deficiency of NADH-cytochrome b reductase activity.&lt;/strong&gt; J. Neurol. Sci. 50: 1-13, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7229653/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7229653&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(81)90038-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7229653">Land et al. (1981)</a> gave a particularly good general review of what was known about the defect in the several mitochondrial myopathies: (1) defects in substrate utilization, as in carnitine deficiency, carnitine palmitoyltransferase deficiency, and defects in various components of the pyruvate dehydrogenase complex; (2) defects in the coupling of mitochondrial respiration to phosphorylation, as in Luft disease and mitochondrial ATPase deficiency; and (3) deficiencies in components of mitochondrial respiratory chain, such as nonheme iron protein, cytochrome oxidase, cytochrome b deficiency, or NADH-CoQ reductase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7229653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="seeAlso" class="mim-anchor"></a>
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<strong>See Also:</strong>
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<a href="#Smeitink1999" class="mim-tip-reference" title="Smeitink, J., van den Heuvel, L. &lt;strong&gt;Human mitochondrial complex I in health and disease.&lt;/strong&gt; Am. J. Hum. Genet. 64: 1505-1510, 1999.">Smeitink and van den Heuvel (1999)</a>
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<a id="references"class="mim-anchor"></a>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
<a id="Anderson2008" class="mim-anchor"></a>
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Anderson, S. L., Chung, W. K., Frezzo, J., Papp, J. C., Ekstein, J., DiMauro, S., Rubin, B. Y.
<strong>A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family.</strong>
J. Inherit. Metab. Dis. 31: S461-S467, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19107570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19107570</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19107570" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s10545-008-1049-9" target="_blank">Full Text</a>]
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<a id="Assereto2014" class="mim-anchor"></a>
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Assereto, S., Robbiano, A., Di Rocco, M., Rossi, A., Cassandrini, D., Panicucci, C., Brigati, G., Biancheri, R., Bruno, C., Minetti, C., Trucks, H., Sander, T., Zara, F., Gazzerro, E.
<strong>Functional characterization of the c.462delA mutation in the NDUFS4 subunit gene of mitochondrial complex I. (Letter)</strong>
Clin. Genet. 86: 99-101, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24020637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24020637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24020637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/cge.12248" target="_blank">Full Text</a>]
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<a id="Barth1989" class="mim-anchor"></a>
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Barth, P. G., Bolhuis, P. A., Wijburg, F. A., Sinjorgo, K. M. C., Ruitenbeek, W., Schutgens, R. B. H.
<strong>Familial mitochondrial complex I deficiency with an abnormal mitochondrial encoded protein.</strong>
J. Inherit. Metab. Dis. 12 (suppl. 2): 355-357, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2512443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2512443</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2512443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF03335421" target="_blank">Full Text</a>]
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<a id="Benit2004" class="mim-anchor"></a>
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Benit, P., Slama, A., Cartault, F., Giurgea, I., Chretien, D., Lebon, S., Marsac, C., Munnich, A., Rotig, A., Rustin, P.
<strong>Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome.</strong>
J. Med. Genet. 41: 14-17, 2004.
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[<a href="https://doi.org/10.1136/jmg.2003.014316" target="_blank">Full Text</a>]
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Benit, P., Steffann, J., Lebon, S., Chretien, D., Kadhom, N., de Lonlay, P., Goldenberg, A., Dumez, Y., Dommergues, M., Rustin, P., Munnich, A., Rotig, A.
<strong>Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome.</strong>
Hum. Genet. 112: 563-566, 2003.
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[<a href="https://doi.org/10.1007/s00439-002-0884-2" target="_blank">Full Text</a>]
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Bentlage, H., de Coo, R., ter Laak, H., Sengers, R., Trijbels, F., Ruitenbeek, W., Schlote, W., Pfeiffer, K., Gencic, S., Von Jagow, G.
<strong>Human diseases with defects in oxidative phosphorylation. I. Decreased amounts of assembled oxidative phosphorylation complexes in mitochondrial encephalomyopathies.</strong>
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[<a href="https://doi.org/10.1111/j.1432-1033.1995.tb20218.x" target="_blank">Full Text</a>]
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Breen, G. A. M., Scheffler, I. E.
<strong>Respiration-deficient Chinese hamster cell mutants: biochemical characterization.</strong>
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[<a href="https://doi.org/10.1007/BF01538879" target="_blank">Full Text</a>]
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Budde, S. M. S., van den Heuvel, L. P. W. J., Janssen, A. J., Smeets, R. J. P., Buskens, C. A. F., DeMeirleir, L., Van Coster, R., Baethmann, M., Voit, T., Trijbels, J. M. F., Smeitink, J. A. M.
<strong>Combined enzymatic complex I and III deficiency associated with mutations in the nuclear encoded NDUFS4 gene.</strong>
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[<a href="https://doi.org/10.1006/bbrc.2000.3257" target="_blank">Full Text</a>]
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Day, C. E., Scheffler, I. E.
<strong>Mapping of the genes of some components of the electron transport chain (complex I) on the X chromosome of mammals.</strong>
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[<a href="https://doi.org/10.1007/BF01543012" target="_blank">Full Text</a>]
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<strong>A respiration-deficient Chinese hamster cell line with a defect in NADH-coenzyme Q reductase.</strong>
J. Biol. Chem. 251: 4588-4595, 1976.
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Dionisi-Vici, C., Ruitenbeek, W., Fariello, G., Bentlage, H., Wanders, R. J., Schagger, H., Bosman, C., Piantadosi, C., Sabetta, G., Bertini, E.
<strong>New familial mitochondrial encephalopathy with macrocephaly, cardiomyopathy, and complex I deficiency.</strong>
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[<a href="https://doi.org/10.1002/ana.410420419" target="_blank">Full Text</a>]
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Ditta, G., Soderberg, K., Landy, F., Scheffler, I. E.
<strong>The selection of Chinese hamster cells deficient in oxidative energy metabolism.</strong>
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[<a href="https://doi.org/10.1007/BF01538838" target="_blank">Full Text</a>]
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Gonzalez-Quintana, A., Trujillo-Tiebas, M. J., Fernandez-Perrone, A. L., Blazquez, A., Lucia, A., Moran, M., Ugalde, C., Arenas, J., Ayuso, C., Martin, M. A.
<strong>Uniparental isodisomy as a cause of mitochondrial complex I respiratory chain disorder due to a novel splicing NDUFS4 mutation.</strong>
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[<a href="https://doi.org/10.1016/j.ymgme.2020.10.008" target="_blank">Full Text</a>]
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Haack, T. B., Haberberger, B., Frisch, E.-M., Wieland, T., Iuso, A., Gorza, M., Strecker, V., Graf, E., Mayr, J. A., Herberg, U., Hennermann, J. B., Klopstock, T., and 16 others.
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[<a href="https://doi.org/10.1136/jmedgenet-2012-100846" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI113066" target="_blank">Full Text</a>]
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Kirby, D. M., Salemi, R., Sugiana, C., Ohtake, A., Parry, L., Bell, K. M., Kirk, E. P., Boneh, A., Taylor, R. W., Dahl, H.-H. M., Ryan, M. T., Thorburn, D. R.
<strong>NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency.</strong>
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[<a href="https://doi.org/10.1172/JCI20683" target="_blank">Full Text</a>]
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Land, J. M., Morgan-Hughes, J. A., Clark, J. B.
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[<a href="https://doi.org/10.1016/0022-510x(81)90038-1" target="_blank">Full Text</a>]
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Lebre, A. S., Rio, M., Faivre d'Arcier, L., Vernerey, D., Landrieu, P., Slama, A., Jardel, C., Laforet, P., Rodriguez, D., Dorison, N., Galanaud, D., Chabrol, B., and 14 others.
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Loeffen, J. L. C. M., Smeitink, J. A. M., Trijbels, J. M. F., Janssen, A. J. M., Triepels, R. H., Sengers, R. C. A., van den Heuvel, L. P.
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(200002)15:2&lt;123::AID-HUMU1&gt;3.0.CO;2-P" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF01549659" target="_blank">Full Text</a>]
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McFarland, R., Kirby, D. M., Fowler, K. J., Ohtake, A., Ryan, M. T., Amor, D. J., Fletcher, J. M., Dixon, J. W., Collins, F. A., Turnbull, D. M., Taylor, R. W., Thorburn, D. R.
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[<a href="https://doi.org/10.1002/ana.10787" target="_blank">Full Text</a>]
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Moreadith, R. W., Batshaw, M. L., Ohnishi, T., Kerr, D., Knox, B., Jackson, D., Hruban, R., Olson, J., Reynafarje, B., Lehninger, A. L.
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[<a href="https://doi.org/10.1172/JCI111484" target="_blank">Full Text</a>]
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Moreadith, R. W., Cleeter, M. W. J., Ragan, C. I., Batshaw, M. L., Lehninger, A. L.
<strong>Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I.</strong>
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[<a href="https://doi.org/10.1172/JCI112834" target="_blank">Full Text</a>]
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Morgan-Hughes, J. A., Darveniza, P., Landon, D. N., Land, J. M., Clark, J. B.
<strong>A mitochondrial myopathy with a deficiency of respiratory chain NADH-CoQ reductase activity.</strong>
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[<a href="https://doi.org/10.1016/0022-510x(79)90071-6" target="_blank">Full Text</a>]
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<strong>A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome.</strong>
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[<a href="https://doi.org/10.1093/hmg/10.5.529" target="_blank">Full Text</a>]
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<a id="26" class="mim-anchor"></a>
<a id="Pitkanen1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pitkanen, S., Feigenbaum, A., Laframboise, R., Robinson, B. H.
<strong>NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings.</strong>
J. Inherit. Metab. Dis. 19: 675-686, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8892026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8892026</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8892026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01799845" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Procaccio1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Procaccio, V., Mousson, B., Beugnot, R., Duborjal, H., Feillet, F., Putet, G., Pignot-Paintrand, I., Lombes, A., De Coo, R., Smeets, H., Lunardi, J., Issartel, J.-P.
<strong>Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts.</strong>
J. Clin. Invest. 104: 83-92, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10393702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10393702</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10393702[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=10393702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI6184" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Robinson1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Robinson, B. H.
<strong>Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect.</strong>
Biochim. Biophys. Acta 1364: 271-286, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9593934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9593934</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9593934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0005-2728(98)00033-4" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Slipetz1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Slipetz, D. M., Goodyer, P. R., Rozen, R.
<strong>Congenital deficiency of a 20-kDA subunit of mitochondrial complex I in fibroblasts.</strong>
Am. J. Hum. Genet. 48: 1121-1126, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1903590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1903590</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1903590" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Smeitink1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Smeitink, J., van den Heuvel, L.
<strong>Human mitochondrial complex I in health and disease.</strong>
Am. J. Hum. Genet. 64: 1505-1510, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10330338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10330338</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10330338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/302432" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="31" class="mim-anchor"></a>
<a id="Soderberg1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Soderberg, K., Mascarello, J. T., Bakay, B., Scheffler, I. E.
<strong>Respiration-deficient Chinese hamster cell mutants: genetic characterization.</strong>
Somat. Cell Genet. 5: 225-240, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/483122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">483122</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=483122" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01539163" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="32" class="mim-anchor"></a>
<a id="Swalwell2011" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Swalwell, H., Kirby, D. M., Blakely, E. L., Mitchell, A., Salemi, R., Sugiana, C., Compton, A. G., Tucker, E. J., Ke, B.-X., Lamont, P. J., Turnbull, D. M., McFarland, R., Taylor, R. W., Thorburn, D. R.
<strong>Respiratory chain complex I deficiency caused by mitochondrial DNA mutations.</strong>
Europ. J. Hum. Genet. 19: 769-775, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21364701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21364701</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21364701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ejhg.2011.18" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Triepels2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Triepels, R. H., van den Heuvel, L. P., Trijbels, J. M., Smeitink, J. A.
<strong>Respiratory chain complex I deficiency.</strong>
Am. J. Med. Genet. 106: 37-45, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11579423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11579423</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11579423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1397" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="van den Heuvel1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
van den Heuvel, L., Ruitenbeek, W., Smeets, R., Gelman-Kohan, Z., Elpeleg, O., Loeffen, J., Trijbels, F., Mariman, E., de Bruijn, D., Smeitink, J.
<strong>Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit.</strong>
Am. J. Hum. Genet. 62: 262-268, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463323</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/301716" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="von Kleist-Retzow1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
von Kleist-Retzow, J.-C., Cormier-Daire, V., de Lonlay, P., Parfait, B., Chretien, D., Rustin, P., Feingold, J., Rotig, A., Munnich, A.
<strong>A high rate (20%-30%) of parental consanguinity in cytochrome-oxidase deficiency.</strong>
Am. J. Hum. Genet. 63: 428-435, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/301957" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="36" class="mim-anchor"></a>
<a id="Whitfield1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Whitfield, C. D., Bostedor, P., Goodman, D., Haak, M., Chu, E. H. Y.
<strong>Increased hexose transport in Chinese hamster ovary cells resistant to 3-O-methyl-D-glucose.</strong>
J. Biol. Chem. 256: 6651-6656, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7240234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7240234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7240234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Wijburg1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wijburg, F. A., Barth, P. G., Ruitenbeek, W., Wanders, R. J. A., Vos, G. D., Ploos van Amstel, S. L. B., Schutgens, R. B. H.
<strong>Familial NADH:Q(1) oxidoreductase (complex I) deficiency: variable expression and possible treatment.</strong>
J. Inherit. Metab. Dis. 12 (suppl. 2): 349-351, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2512441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2512441</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2512441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF03335419" target="_blank">Full Text</a>]
</p>
</div>
</li>
</ol>
<div>
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<div>
<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 02/12/2021
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseContributors">
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Carol A. Bocchini - updated : 12/13/2018<br>Cassandra L. Kniffin - updated : 11/08/2017<br>Cassandra L. Kniffin - updated : 06/27/2017<br>Cassandra L. Kniffin - updated : 07/26/2016<br>Cassandra L. Kniffin - updated : 9/17/2013<br>Cassandra L. Kniffin - updated : 5/23/2013<br>Cassandra L. Kniffin - updated : 5/1/2013<br>Cassandra L. Kniffin - updated : 2/13/2013<br>Cassandra L. Kniffin - updated : 11/29/2012<br>Cassandra L. Kniffin - updated : 6/12/2012<br>Cassandra L. Kniffin - updated : 2/1/2012<br>Cassandra L. Kniffin - updated : 12/13/2011<br>George E. Tiller - updated : 10/25/2011<br>Cassandra L. Kniffin - updated : 10/12/2011<br>Cassandra L. Kniffin - updated : 11/2/2010<br>Cassandra L. Kniffin - updated : 9/27/2010<br>Cassandra L. Kniffin - updated : 1/25/2010<br>Cassandra L. Kniffin - updated : 10/19/2009<br>Cassandra L. Kniffin - updated : 7/22/2009<br>Cassandra L. Kniffin - updated : 3/23/2009<br>Cassandra L. Kniffin - updated : 10/27/2008<br>Victor A. McKusick - updated : 2/19/2008<br>Cassandra L. Kniffin - updated : 9/10/2007<br>Cassandra L. Kniffin - updated : 11/7/2006<br>Anne M. Stumpf - updated : 11/10/2005<br>Cassandra L. Kniffin - updated : 10/17/2005<br>Cassandra L. Kniffin - reorganized : 9/21/2005<br>Cassandra L. Kniffin - updated : 8/30/2005<br>Cassandra L. Kniffin - updated : 1/5/2005<br>Marla J. F. O'Neill - updated : 10/14/2004<br>Ada Hamosh - updated : 1/29/2002<br>Victor A. McKusick - updated : 7/24/2001<br>Victor A. McKusick - updated : 2/22/2000<br>Victor A. McKusick - updated : 8/12/1999<br>Victor A. McKusick - updated : 6/18/1999<br>Victor A. McKusick - updated : 5/28/1999<br>Victor A. McKusick - updated : 9/11/1998
</span>
</div>
</div>
</div>
<div>
<a id="creationDate" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 9/30/1987
</span>
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<div>
<a id="editHistory" class="mim-anchor"></a>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 12/18/2023
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<div class="row collapse" id="mimCollapseEditHistory">
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 11/23/2022<br>carol : 02/25/2022<br>carol : 06/15/2021<br>carol : 02/12/2021<br>carol : 02/09/2021<br>ckniffin : 01/28/2021<br>carol : 10/18/2020<br>carol : 09/04/2020<br>ckniffin : 09/04/2020<br>alopez : 02/19/2020<br>ckniffin : 02/15/2020<br>carol : 03/25/2019<br>carol : 03/22/2019<br>carol : 02/04/2019<br>carol : 01/09/2019<br>carol : 12/14/2018<br>carol : 12/13/2018<br>carol : 10/31/2018<br>carol : 10/11/2018<br>ckniffin : 10/11/2018<br>alopez : 07/05/2018<br>ckniffin : 06/27/2018<br>carol : 03/16/2018<br>carol : 03/15/2018<br>ckniffin : 03/15/2018<br>carol : 11/10/2017<br>alopez : 11/09/2017<br>ckniffin : 11/08/2017<br>ckniffin : 06/27/2017<br>carol : 12/05/2016<br>ckniffin : 12/01/2016<br>alopez : 08/12/2016<br>carol : 07/29/2016<br>ckniffin : 07/26/2016<br>carol : 09/24/2013<br>carol : 9/24/2013<br>ckniffin : 9/17/2013<br>carol : 6/7/2013<br>ckniffin : 5/23/2013<br>ckniffin : 5/8/2013<br>carol : 5/2/2013<br>ckniffin : 5/1/2013<br>carol : 2/26/2013<br>ckniffin : 2/13/2013<br>carol : 12/4/2012<br>ckniffin : 11/29/2012<br>ckniffin : 8/7/2012<br>alopez : 6/18/2012<br>ckniffin : 6/12/2012<br>carol : 2/3/2012<br>terry : 2/2/2012<br>ckniffin : 2/1/2012<br>carol : 12/16/2011<br>ckniffin : 12/14/2011<br>ckniffin : 12/13/2011<br>alopez : 10/25/2011<br>carol : 10/13/2011<br>ckniffin : 10/12/2011<br>wwang : 7/20/2011<br>ckniffin : 7/7/2011<br>wwang : 5/17/2011<br>ckniffin : 5/16/2011<br>alopez : 11/2/2010<br>ckniffin : 11/2/2010<br>wwang : 9/28/2010<br>ckniffin : 9/27/2010<br>ckniffin : 9/24/2010<br>wwang : 1/29/2010<br>ckniffin : 1/25/2010<br>ckniffin : 1/25/2010<br>wwang : 11/12/2009<br>ckniffin : 10/19/2009<br>wwang : 8/4/2009<br>ckniffin : 7/22/2009<br>wwang : 4/9/2009<br>ckniffin : 3/23/2009<br>wwang : 11/3/2008<br>ckniffin : 10/27/2008<br>wwang : 9/16/2008<br>ckniffin : 9/10/2008<br>alopez : 2/22/2008<br>terry : 2/19/2008<br>wwang : 9/13/2007<br>ckniffin : 9/10/2007<br>wwang : 6/26/2007<br>terry : 6/22/2007<br>wwang : 2/19/2007<br>ckniffin : 2/15/2007<br>wwang : 11/10/2006<br>ckniffin : 11/7/2006<br>alopez : 11/10/2005<br>ckniffin : 10/17/2005<br>carol : 9/21/2005<br>ckniffin : 8/30/2005<br>terry : 4/6/2005<br>alopez : 3/9/2005<br>tkritzer : 1/12/2005<br>ckniffin : 1/5/2005<br>carol : 11/2/2004<br>terry : 10/14/2004<br>mgross : 8/6/2004<br>ckniffin : 7/7/2003<br>alopez : 1/31/2002<br>terry : 1/29/2002<br>mcapotos : 8/8/2001<br>mcapotos : 7/31/2001<br>terry : 7/24/2001<br>mgross : 6/20/2001<br>terry : 6/20/2001<br>mcapotos : 7/25/2000<br>mcapotos : 7/25/2000<br>mcapotos : 3/23/2000<br>mcapotos : 3/22/2000<br>mcapotos : 3/14/2000<br>terry : 2/22/2000<br>carol : 8/17/1999<br>jlewis : 8/12/1999<br>terry : 6/18/1999<br>mgross : 6/14/1999<br>mgross : 6/8/1999<br>terry : 5/28/1999<br>terry : 9/11/1998<br>alopez : 7/28/1997<br>mimadm : 2/19/1994<br>carol : 7/1/1993<br>supermim : 3/17/1992<br>supermim : 3/20/1990<br>carol : 12/20/1989<br>carol : 12/9/1989
</span>
</div>
</div>
</div>
</div>
</div>
</div>
<div class="container visible-print-block">
<div class="row">
<div class="col-md-8 col-md-offset-1">
<div>
<div>
<h3>
<span class="mim-font">
<strong>#</strong> 252010
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 1; MC1DN1
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
MITOCHONDRIAL COMPLEX I DEFICIENCY<br />
NADH:Q(1) OXIDOREDUCTASE DEFICIENCY<br />
NADH-COENZYME Q REDUCTASE DEFICIENCY<br />
MITOCHONDRIAL NADH DEHYDROGENASE COMPONENT OF COMPLEX I, DEFICIENCY OF
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 237988006; &nbsp;
<strong>ORPHA:</strong> 2609; &nbsp;
<strong>DO:</strong> 0112074; &nbsp;
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
5q11.2
</span>
</td>
<td>
<span class="mim-font">
Mitochondrial complex I deficiency, nuclear type 1
</span>
</td>
<td>
<span class="mim-font">
252010
</span>
</td>
<td>
<span class="mim-font">
Autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
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NDUFS4
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602694
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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 I deficiency nuclear type 1 (MC1DN1) is caused by homozygous mutation in the NDUFS4 gene (602694) on chromosome 5q11.</p>
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<strong>Description</strong>
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<p>Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (see 256000), Leber hereditary optic neuropathy (535000), and some forms of Parkinson disease (see 556500) (Loeffen et al., 2000; Pitkanen et al., 1996; Robinson, 1998). </p><p><strong><em>Genetic Heterogeneity of Complex I Deficiency</em></strong></p><p>
Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible (summary by Haack et al., 2012). However, the majority of cases are caused by mutations in nuclear-encoded genes (Loeffen et al., 2000; Triepels et al., 2001). </p><p>Complex I deficiency resulting from mutation in nuclear-encoded genes include MC1DN1, caused by mutation in the NDUFS4 gene (602694); MC1DN2 (618222), caused by mutation in the NDUFS8 gene (602141); MC1DN3 (618224), caused by mutation in the NDUFS7 gene (601825); MC1DN4 (618225), caused by mutation in the NDUFV1 gene (161015); MC1DN5 (618226), caused by mutation in the NDUFS1 gene (157655); MC1DN6 (618228), caused by mutation in the NDUFS2 gene (602985); MC1DN7 (618229), caused by mutation in the NDUFV2 gene (600532); MC1DN8 (618230), caused by mutation in the NDUFS3 gene (603846); MC1DN9 (618232), caused by mutation in the NDUFS6 gene (603848); MC1DN10 (618233), caused by mutation in the NDUFAF2 gene (609653); MC1DN11 (618234), caused by mutation in the NDUFAF1 gene (606934); MC1DN12 (301020), caused by mutation in the NDUFA1 gene (300078); MC1DN13 (618235), caused by mutation in the NDUFA2 gene (602137); MC1DN14 (618236), caused by mutation in the NDUFA11 gene (612638); MC1DN15 (618237), caused by mutation in the NDUFAF4 gene (611776); MC1DN16 (618238), caused by mutation in the NDUFAF5 gene (612360); MC1DN17 (618239), caused by mutation in the NDUFAF6 gene (612392); MC1DN18 (618240), caused by mutation in the NDUFAF3 gene (612911); MC1DN19 (618241), caused by mutation in the FOXRED1 gene (613622); MC1DN20 (611126), caused by mutation in the ACAD9 gene (611103); MC1DN21 (618242), caused by mutation in the NUBPL gene (613621); MC1DN22 (618243), caused by mutation in the NDUFA10 gene (603835); MC1DN23 (618244), caused by mutation in the NDUFA12 gene (614530); MC1DN24 (618245), caused by mutation in the NDUFB9 gene (601445); MC1DN25 (618246), caused by mutation in the NDUFB3 gene (603839); MC1DN26 (618247), caused by mutation in the NDUFA9 gene (603834); MC1DN27 (618248), caused by mutation in the MTFMT gene (611766); MC1DN28 (618249), caused by mutation in the NDUFA13 gene (609435); MC1DN29 (618250), caused by mutation in the TMEM126B gene (615533); MC1DN30 (301021), caused by mutation in the NDUFB11 gene (300403); MC1DN31 (618251), caused by mutation in the TIMMDC1 gene (615534); MC1DN32 (618252), caused by mutation in the NDUFB8 gene (602140); MC1DN33 (618253), caused by mutation in the NDUFA6 gene (602138); MC1DN34 (618776), caused by mutation in the NDUFAF8 gene (618461); MC1DN35 (619003), caused by mutation in the NDUFB10 gene (603843); MC1DN36 (619170), caused by mutation in the NDUFC2 gene (603845); MC1DN37 (619272), caused by mutation in the NDUFA8 gene (603359); MC1DN38 (619382), caused by mutation in the DNAJC30 gene (618202); and MC1DN39 (620135), caused by mutation in the NDUFB7 gene (603842).</p><p>Complex I deficiency with mitochondrial inheritance has been associated with mutation in 6 mitochondrial-encoded components of complex I: MTND1 (516000), MTND2 (516001), MTND3 (516002), MTND4 (516003), MTND5 (516005), MTND6 (516006). Most of these patients have a phenotype of Leber hereditary optic neuropathy (LHON; 535000) or Leigh syndrome. Features of complex I deficiency may also be caused by mutation in other mitochondrial genes, including MTTS2 (590085).</p>
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<strong>Clinical Features</strong>
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<p>Van den Heuvel et al. (1998) reported a patient with fatal multisystemic complex I deficiency and homozygous mutation in the NDUFS4 gene. He had normal muscle morphology and a remarkably nonspecific fatally progressive course without increased lactate concentrations in body fluids. He presented at 8 months of age with severe vomiting, failure to thrive, and hypotonia. At the age of 13 months, he showed severe psychomotor retardation, convulsions, bradypnea, cyanosis, hypotonia, and depressed tendon reflexes. Cerebral MRI showed generalized brain atrophy and symmetric basal ganglia abnormalities. He died of cardiorespiratory failure at the age of 16 months. </p><p>Budde et al. (2000) reported 2 unrelated patients, born to consanguineous parents, with complex I deficiency and decreased activity of complex III. The female patient showed, within 1 week of age, hypotonia, absent eye contact, lethargy, and failure to thrive. At 3 months of age, microcephaly was present and lactic acidemia with an increased lactate/pyruvate ratio was found. CT and MRI showed bilateral basal ganglia hypodensities. The child died at 3 months of age. Except for hypospadias noted at birth, the male patient appeared normal until the age of 7 weeks at which time muscular hypotonia and lack of visual and auditive attention were observed. At the age of 3 months he was found to have elevated lactate levels in the blood. Cranial MRI showed hyperintense signals resembling those found in Leigh syndrome (see 256000). Cardiac ultrasound showed concentric hypertrophy of the left ventricle with hypercontractility. He died from cardiocirculatory insufficiency. </p><p>Petruzzella et al. (2001) reported a girl who after birth showed failure to thrive, psychomotor delay, hypotonia, seizures, lactic acidosis, cardiomyopathy, and basal ganglia lesions on ultrasound. She died at 7 months of age from respiratory failure. </p><p>Benit et al. (2003) identified 2 sisters in a consanguineous family with complex I deficiency nuclear type 1 and Leigh syndrome. </p><p>Gonzalez-Quintana et al. (2020) reported a 7-year-old girl with a history of neonatal macrocephaly who presented with hypotonia, psychomotor delay, and exotropia at 6 months of age. Brain MRI at age 9 months showed abnormal signal in the vestibular nuclei and medial lemniscus, frontal bilateral polymicrogyria, and external hydrocephaly. At age 11 months, she had myoclonus of her arms. Laboratory studies showed lactic acidosis in serum and cerebral spinal fluid. Skeletal muscle biopsy showed type II fiber atrophy and an isolated defect of mitochondrial complex I activity. </p><p><strong><em>Neuroradiologic Features in Patients with Known Nuclear or Mitochondrial Mutations</em></strong></p><p>
Lebre et al. (2011) performed a retrospective review of the neuroradiologic features of 30 patients with complex I deficiency due to either nuclear (10 patients) or mitochondrial (20 patients) mutations. All patients had MRI abnormalities in the brainstem that were hyperintense on T2-weighted images and hypointense on T1-weighted images. Brainstem lesions were associated with at least 1 striatal anomaly (putamen or caudate) in 27 of 30 patients. Ten patients had thalamic anomalies, all of whom also had striatal lesions. Caudate lesions were more common in patients with mtDNA (50%) compared to those with nuclear (10%) mutations. Stroke-like lesions predominantly affecting the gray matter were observed in 40% of patients with mtDNA mutations, but in none of patients with nuclear mutations. A diffuse supratentorial leukoencephalopathy involving the deep lobar white matter was observed in over 50% of patients with nuclear mutations, but in none of patients with mtDNA mutations. Cerebellar hyperintensities were found in 45% of patients, regardless of the mutated genome, but cerebellar atrophy was found only in those with mtDNA mutations. All 10 patients studied had increased lactate on magnetic resonance spectroscopy. </p><p><strong><em>Patients with Unknown Mutations</em></strong></p><p>
Morgan-Hughes et al. (1979) presented the first report of isolated complex I deficiency. Two sisters had a mitochondrial myopathy characterized by weakness, marked exercise intolerance, and fluctuating lactic acidemia. Increased weakness was precipitated by unaccustomed exertion, fasting, or alcohol. During exercise, blood lactate and pyruvate levels rose abruptly and markedly. Mitochondrial respiratory rates were greatly decreased with all NAD-linked substrates, but normal with succinate and with TMPD plus ascorbate. Mitochondrial cytochrome components were normal. Morgan-Hughes et al. (1979) concluded that the defect was at the level of the NADH-CoQ reductase complex. </p><p>Land et al. (1981) reported a young man with weakness, exercise intolerance, muscle wasting, and exercise-induced lactic acidosis. Biochemical studies showed deficiency of NADH-cytochrome b reductase. The defect appeared to be situated between NADH dehydrogenase and the CoQ-cytochrome b complex. Land et al. (1981) postulated a derangement of a nonheme iron-sulfur center. </p><p>Moreadith et al. (1984) reported a male infant with complex I deficiency who developed respiratory distress and hypoglycemia on the first day of life. At 6 weeks, he showed generalized hypotonia and concentric biventricular cardiac hypertrophy on echocardiography. Lactic acidemia was progressive, and the child died at 16 weeks of age. Skeletal muscle biopsy showed giant mitochondria in which both inner and outer membranes were arranged in whorls. Biochemical studies of mitochondria from 4 organs showed a moderate to profound decrease in the ability to oxidize pyruvate, malate plus glutamate, citrate and other NAD-linked respiratory substrates. Oxidation of succinate was normal. Further studies localized the defect to the inner membrane mitochondrial NADH-ubiquinone oxidoreductase. Electron paramagnetic resonance spectroscopy showed almost total loss of the iron-sulfur clusters of complex I. The most pronounced deficiency was in skeletal muscle, the least in kidney mitochondria. There was no record of a similar problem in the family and the parents were not related. Since the parents subsequently had a normal male child, Moreadith et al. (1984) excluded mitochondrial inheritance and suggested either autosomal recessive inheritance or a de novo dominant mutation. </p><p>In a study on tissue from the patient reported by Moreadith et al. (1984), Moreadith et al. (1987) found that antisera against complex I immunoprecipitated NADH-ferricyanide reductase from the control but not the patient's mitochondria. Immunoprecipitation and SDS-PAGE of complex I polypeptides demonstrated that most of the 25 polypeptides comprising complex I were present in the affected mitochondria. A more detailed analysis using subunit selective antisera against the main polypeptides of the iron-protein fragments of complex I showed a selective absence of the 75- and 13-kD polypeptides, suggesting a deficiency of at least 2 polypeptides comprising the iron-protein fragment of complex I. Moreadith et al. (1987) hypothesized that the genetic defect involved transcription or translation of the polypeptides, the transport of these polypeptides into the mitochondria, or the site of assembly of complex I. </p><p>Hoppel et al. (1987) investigated a mitochondrial defect in a male infant with fatal congenital lactic acidosis, high lactate-to-pyruvate ratio, hypotonia, and cardiomyopathy. His sister had died with a similar disorder. Resting oxygen consumption was 150% of controls. Pathologic findings included increased numbers of skeletal muscle mitochondria (many with proliferated, concentric cristae), cardiomegaly, fatty infiltration of the viscera, and spongy encephalopathy. Mitochondria from liver and muscle biopsies oxidized NADH-linked substrates at rates 20 to 50% of controls, whereas succinate oxidation by muscle mitochondria was increased. Mitochondrial NADH dehydrogenase activity (complex I) was 0 to 10% of controls, whereas activity of other electron transport complexes in related enzymes was normal. Hoppel et al. (1987) suggested a familial deficiency of a component of mitochondrial NADH dehydrogenase proximal to the rotenone-sensitive site. </p><p>Wijburg et al. (1989) reported a sibship born to healthy first-cousin Moroccan parents with 2 well-studied children with severe congenital lactic acidosis as well as 4 others with a clinical history compatible with the same defect. Treatment initially by artificial respiration and peritoneal dialysis followed later by high doses of menadione effected a remarkable recovery. Despite the parental consanguinity, Barth et al. (1989) suggested that the defect in this family involved the mitochondrial genome: they detected a possible deletion in the mitochondrial-encoded MTND3 protein in skeletal muscle. </p><p>Slipetz et al. (1991) studied 2 unrelated patients with complex I deficiency with different phenotypes. One patient had hypotonia, seizures, and hepatomegaly, and died of lactic acidosis on day 13 of life. Biochemical analysis of complex I subunits showed absence of a 20-kD protein predicted to be encoded by the nuclear genome. Complex I activity was 6% of control values. The other child had marked growth and developmental delay, and showed altered neurologic function and seizures beginning at age 8 years. Other features included ptosis, sensorineural hearing loss, hypotonia, incoordination, and hyporeflexia. Mild facial coarseness was also observed. No complex I subunit abnormalities were detected by immunoprecipitation or Western blot analysis, but complex I activity was 15% of control values. </p><p>Bentlage et al. (1995) showed deficits of specific complex I protein subunits in patients with complex I deficiency. </p><p>Dionisi-Vici et al. (1997) reported 2 infant sibs with fatal progressive macrocephaly and hypertrophic cardiomyopathy. Onset of symptoms was at the end of the first month of life with massive brain swelling. Light microscopy showed extensive small-vessel proliferation and gliosis. Complex I deficiency was detected in cultured fibroblasts, skeletal muscle, and heart muscle. </p><p>Procaccio et al. (1999) reported 2 unrelated patients with fatal infantile lactic acidosis associated with isolated complex I deficiency. Reexpression of complex I subunits and recovery of complex I activity in patients' mitochondria after transnuclear complementation by nuclei from cells without mitochondria enabled the authors to infer the nuclear DNA origin of the defects in both patients. Patient 1 showed reduced amounts of the 24- and 51-kD subunits and normal amounts of all the other investigated subunits. Patient 2 showed severely decreased amounts of all the investigated subunits. Patient 1 developed generalized hypotonia with poor gesticulation in the first 24 hours of life. By day 2, he was very floppy with poor response to painful stimuli and required ventilatory assistance. Hepatic enlargement was noticed, and chest x-rays showed slight cardiomegaly. Cranial ultrasonography showed brain edema, and severe lactic acidosis was detected. The patient went into a deep coma and died at 11 days. Patient 2 vomited frequently in the first 2 weeks of life and at 5 weeks showed deterioration of neurologic status with hypotonia, weakness, and lethargy. In the first month, the head circumference was noted to be rapidly increasing from 33 to 40 cm. Computed tomographic scan showed a very hypodense brain with increased brain volume and extensive cerebral edema. Marked metabolic acidosis with hyperlactic acidemia was demonstrated. Despite intensive care, the neurologic state worsened rapidly and brain death occurred at 6 weeks of age. Autopsy showed acute necrotizing encephalopathy, but no hypertrophic cardiomyopathy. </p><p>In a study of 157 patients with respiratory chain defects, von Kleist-Retzow et al. (1998) found complex I deficiency in 33% and combined complex I and IV deficiency in another 28%. The main clinical features in this series were truncal hypotonia (36%), antenatal (20%) and postnatal (31%) growth retardation, cardiomyopathy (24%), encephalopathy (20%), and liver failure (20%). No correlation was found between the type of respiratory chain defect and the clinical presentation, but complex I and complex I+IV deficiencies were significantly more frequent in cases of cardiomyopathy (p less than 0.01) and hepatic failure (p less than 0.05), respectively. The sex ratio was skewed toward males being affected with complex I deficiency. A high rate of parental consanguinity was observed in complex IV (20%) and complex I+IV (28%) deficiencies. </p><p>Loeffen et al. (2000) retrospectively examined clinical and biochemical characteristics of 27 patients, all of whom presented in infancy and young childhood with isolated enzymatic complex I deficiency established in cultured skin fibroblasts; common pathogenic mtDNA point mutations and major rearrangements were absent. Clinical phenotypes included Leigh syndrome in 7 patients, Leigh-like syndrome in 6, fatal infantile lactic acidosis in 3, neonatal cardiomyopathy with lactic acidosis in 3, macrocephaly with progressive leukodystrophy in 2, and a residual group of unspecified encephalomyopathy in 6, subdivided into progressive (in 4) and stable (in 2) variants. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of MC1DN1 in the patient reported by van den Heuvel et al. (1998) was consistent with autosomal recessive inheritance. </p>
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<strong>Molecular Genetics</strong>
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<p>In 1 of 20 patients with complex I deficiency nuclear type 1, van den Heuvel et al. (1998) identified a homozygous 5-bp duplication in the NDUFS4 gene (602694.0001). The parents were heterozygous for the mutation. </p><p>In 2 unrelated patients with complex I deficiency nuclear type 1 and decreased activity of complex III, Budde et al. (2000) demonstrated homozygous mutations in the NDUFS4 gene (602694.0002 and 602694.0003). The mutations segregated with the disorder in both families. </p><p>In a patient with complex I deficiency presenting as Leigh syndrome, Petruzzella et al. (2001) identified a homozygous nonsense mutation in the NDUFS4 cDNA (W15X; 602694.0004). Both parents were heterozygous for the mutation. </p><p>In 2 sisters in a consanguineous family with complex I deficiency and Leigh syndrome, Benit et al. (2003) identified a homozygous splice site mutation in the NDUFS4 locus (602694.0005). </p><p>In 3 sibs, born of Ashkenazi Jewish parents, with complex I deficiency nuclear type 1 manifesting as Leigh syndrome, Anderson et al. (2008) identified a homozygous 1-bp deletion (462delA; 602694.0006) in the NDUFS4 gene. The mutation was identified by linkage analysis followed by candidate gene sequencing. Each unaffected parent and an unaffected sib were heterozygous for the mutation. The carrier frequency of the mutation, ascertained from 5,000 controls of Ashkenazi Jewish descent, was found to be 1 in 1,000, consistent with a founder effect in this population. Based on the results, Anderson et al. (2008) used prenatal testing in this family to help the parents produce an unaffected child. </p><p>Assereto et al. (2014) identified homozygosity for the 462delA mutation in the NDUFS4 gene in 2 sibs with mitochondrial complex I deficiency who were not of Ashkenazi Jewish descent. </p><p>Gonzalez-Quintana et al. (2020) identified homozygosity for a splicing mutation (602694.0007) in the NDUFS4 gene in a 7-year-old girl with MC1DN1. The patient's father carried the mutation, but her mother did not. Short tandem repeat analysis of DNA from the patient and her parents showed that homozygosity was caused by paternal uniparental disomy. Analysis of muscle and fibroblast cDNA from the patient showed reduced expression of NDUFS4, and several abnormal NDUFS4 transcripts were identified in the patient's muscle, indicative of abnormal splicing. </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>Mutations in the nuclear-encoded genes NDUFS1, NDUFS4, NDUFS7, NDUFS8, and NDUFV1 result in neurologic diseases, mostly Leigh syndrome or Leigh-like syndrome. Mutations in NDUFS2 and NDUFV2 have been associated with hypertrophic cardiomyopathy and encephalomyopathy. Mutations in the mitochondrial-encoded genes are associated with a wide variety of clinical symptoms, ranging from organ-specific to multisystem diseases (Benit et al., 2004). </p><p>Swalwell et al. (2011) reviewed the clinical and genetic findings in a large cohort of 109 pediatric patients with isolated complex I deficiency from 101 families. Pathogenic mtDNA mutations were found in 29% of probands: 21 in MTND subunit genes and 8 in mtDNA tRNA genes. Nuclear gene defects were inferred in 38% of probands based on cell hybrid studies, mtDNA sequencing, or mutation analysis. The most common clinical presentation was Leigh or Leigh-like disease in patients with either mtDNA or nuclear genetic defects. The median age at onset was later in mtDNA patients (12 months) compared to patients with a nuclear gene defect (3 months), although there was considerable overlap. The report confirmed that pathogenic mtDNA mutations are a significant cause of complex I deficiency in children. </p>
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<strong>Animal Model</strong>
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<p>The laboratory of Scheffler (DeFrancesco et al., 1976; Ditta et al., 1976; Breen and Scheffler, 1979; Soderberg et al., 1979) described several respiration-deficient mutants of Chinese hamster cells in culture. All depended on an ample supply of glucose in the medium to sustain a high rate of glycolysis. When galactose was substituted for glucose, the mutants died. This property was used to sort about 3 dozen mutants into 7 complementation groups (Soderberg et al., 1979). Whitfield et al. (1981) and Maiti et al. (1981) also identified gal-minus mutants in Chinese hamster cells that had a defect in the electron-transport chain. Specifically, several of the complementation groups appeared to be defective in complex I of the electron transport chain. Day and Scheffler (1982) reported that some of these complementation groups were X-linked in the hamster and mouse. The gene locus (-i) was symbolized 'res.' At least one complementation group was found to be autosomal. </p>
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<strong>History</strong>
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<p>Land et al. (1981) gave a particularly good general review of what was known about the defect in the several mitochondrial myopathies: (1) defects in substrate utilization, as in carnitine deficiency, carnitine palmitoyltransferase deficiency, and defects in various components of the pyruvate dehydrogenase complex; (2) defects in the coupling of mitochondrial respiration to phosphorylation, as in Luft disease and mitochondrial ATPase deficiency; and (3) deficiencies in components of mitochondrial respiratory chain, such as nonheme iron protein, cytochrome oxidase, cytochrome b deficiency, or NADH-CoQ reductase. </p>
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<h4>
<span class="mim-font">
<strong>See Also:</strong>
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</h4>
<span class="mim-text-font">
Smeitink and van den Heuvel (1999)
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<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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</h4>
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<p />
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<div>
<ol>
<li>
<p class="mim-text-font">
Anderson, S. L., Chung, W. K., Frezzo, J., Papp, J. C., Ekstein, J., DiMauro, S., Rubin, B. Y.
<strong>A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family.</strong>
J. Inherit. Metab. Dis. 31: S461-S467, 2008.
[PubMed: 19107570]
[Full Text: https://doi.org/10.1007/s10545-008-1049-9]
</p>
</li>
<li>
<p class="mim-text-font">
Assereto, S., Robbiano, A., Di Rocco, M., Rossi, A., Cassandrini, D., Panicucci, C., Brigati, G., Biancheri, R., Bruno, C., Minetti, C., Trucks, H., Sander, T., Zara, F., Gazzerro, E.
<strong>Functional characterization of the c.462delA mutation in the NDUFS4 subunit gene of mitochondrial complex I. (Letter)</strong>
Clin. Genet. 86: 99-101, 2014.
[PubMed: 24020637]
[Full Text: https://doi.org/10.1111/cge.12248]
</p>
</li>
<li>
<p class="mim-text-font">
Barth, P. G., Bolhuis, P. A., Wijburg, F. A., Sinjorgo, K. M. C., Ruitenbeek, W., Schutgens, R. B. H.
<strong>Familial mitochondrial complex I deficiency with an abnormal mitochondrial encoded protein.</strong>
J. Inherit. Metab. Dis. 12 (suppl. 2): 355-357, 1989.
[PubMed: 2512443]
[Full Text: https://doi.org/10.1007/BF03335421]
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</li>
<li>
<p class="mim-text-font">
Benit, P., Slama, A., Cartault, F., Giurgea, I., Chretien, D., Lebon, S., Marsac, C., Munnich, A., Rotig, A., Rustin, P.
<strong>Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome.</strong>
J. Med. Genet. 41: 14-17, 2004.
[PubMed: 14729820]
[Full Text: https://doi.org/10.1136/jmg.2003.014316]
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</li>
<li>
<p class="mim-text-font">
Benit, P., Steffann, J., Lebon, S., Chretien, D., Kadhom, N., de Lonlay, P., Goldenberg, A., Dumez, Y., Dommergues, M., Rustin, P., Munnich, A., Rotig, A.
<strong>Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome.</strong>
Hum. Genet. 112: 563-566, 2003.
[PubMed: 12616398]
[Full Text: https://doi.org/10.1007/s00439-002-0884-2]
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<li>
<p class="mim-text-font">
Bentlage, H., de Coo, R., ter Laak, H., Sengers, R., Trijbels, F., Ruitenbeek, W., Schlote, W., Pfeiffer, K., Gencic, S., Von Jagow, G.
<strong>Human diseases with defects in oxidative phosphorylation. I. Decreased amounts of assembled oxidative phosphorylation complexes in mitochondrial encephalomyopathies.</strong>
Europ. J. Biochem. 227: 909-915, 1995.
[PubMed: 7867654]
[Full Text: https://doi.org/10.1111/j.1432-1033.1995.tb20218.x]
</p>
</li>
<li>
<p class="mim-text-font">
Breen, G. A. M., Scheffler, I. E.
<strong>Respiration-deficient Chinese hamster cell mutants: biochemical characterization.</strong>
Somat. Cell Genet. 5: 441-451, 1979.
[PubMed: 494059]
[Full Text: https://doi.org/10.1007/BF01538879]
</p>
</li>
<li>
<p class="mim-text-font">
Budde, S. M. S., van den Heuvel, L. P. W. J., Janssen, A. J., Smeets, R. J. P., Buskens, C. A. F., DeMeirleir, L., Van Coster, R., Baethmann, M., Voit, T., Trijbels, J. M. F., Smeitink, J. A. M.
<strong>Combined enzymatic complex I and III deficiency associated with mutations in the nuclear encoded NDUFS4 gene.</strong>
Biochem. Biophys. Res. Commun. 275: 63-68, 2000.
[PubMed: 10944442]
[Full Text: https://doi.org/10.1006/bbrc.2000.3257]
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<li>
<p class="mim-text-font">
Day, C. E., Scheffler, I. E.
<strong>Mapping of the genes of some components of the electron transport chain (complex I) on the X chromosome of mammals.</strong>
Somat. Cell Genet. 8: 691-707, 1982.
[PubMed: 6819642]
[Full Text: https://doi.org/10.1007/BF01543012]
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</li>
<li>
<p class="mim-text-font">
DeFrancesco, L., Scheffler, I. E., Bissell, M. J.
<strong>A respiration-deficient Chinese hamster cell line with a defect in NADH-coenzyme Q reductase.</strong>
J. Biol. Chem. 251: 4588-4595, 1976.
[PubMed: 947896]
</p>
</li>
<li>
<p class="mim-text-font">
Dionisi-Vici, C., Ruitenbeek, W., Fariello, G., Bentlage, H., Wanders, R. J., Schagger, H., Bosman, C., Piantadosi, C., Sabetta, G., Bertini, E.
<strong>New familial mitochondrial encephalopathy with macrocephaly, cardiomyopathy, and complex I deficiency.</strong>
Ann. Neurol. 42: 661-665, 1997.
[PubMed: 9382480]
[Full Text: https://doi.org/10.1002/ana.410420419]
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</li>
<li>
<p class="mim-text-font">
Ditta, G., Soderberg, K., Landy, F., Scheffler, I. E.
<strong>The selection of Chinese hamster cells deficient in oxidative energy metabolism.</strong>
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</p>
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Haack, T. B., Haberberger, B., Frisch, E.-M., Wieland, T., Iuso, A., Gorza, M., Strecker, V., Graf, E., Mayr, J. A., Herberg, U., Hennermann, J. B., Klopstock, T., and 16 others.
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<strong>Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport: fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy.</strong>
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[PubMed: 3110216]
[Full Text: https://doi.org/10.1172/JCI113066]
</p>
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Lebre, A. S., Rio, M., Faivre d'Arcier, L., Vernerey, D., Landrieu, P., Slama, A., Jardel, C., Laforet, P., Rodriguez, D., Dorison, N., Galanaud, D., Chabrol, B., and 14 others.
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Loeffen, J. L. C. M., Smeitink, J. A. M., Trijbels, J. M. F., Janssen, A. J. M., Triepels, R. H., Sengers, R. C. A., van den Heuvel, L. P.
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<p class="mim-text-font">
Maiti, I. B., Comlan de Souza, A., Thirion, J. P.
<strong>Biochemical and genetic characterization of respiration-deficient mutants of Chinese hamster cells with a Gal-phenotype.</strong>
Somat. Cell Genet. 7: 567-582, 1981.
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McFarland, R., Kirby, D. M., Fowler, K. J., Ohtake, A., Ryan, M. T., Amor, D. J., Fletcher, J. M., Dixon, J. W., Collins, F. A., Turnbull, D. M., Taylor, R. W., Thorburn, D. R.
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[PubMed: 14705112]
[Full Text: https://doi.org/10.1002/ana.10787]
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Moreadith, R. W., Batshaw, M. L., Ohnishi, T., Kerr, D., Knox, B., Jackson, D., Hruban, R., Olson, J., Reynafarje, B., Lehninger, A. L.
<strong>Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.</strong>
J. Clin. Invest. 74: 685-697, 1984.
[PubMed: 6432847]
[Full Text: https://doi.org/10.1172/JCI111484]
</p>
</li>
<li>
<p class="mim-text-font">
Moreadith, R. W., Cleeter, M. W. J., Ragan, C. I., Batshaw, M. L., Lehninger, A. L.
<strong>Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I.</strong>
J. Clin. Invest. 79: 463-467, 1987.
[PubMed: 3100577]
[Full Text: https://doi.org/10.1172/JCI112834]
</p>
</li>
<li>
<p class="mim-text-font">
Morgan-Hughes, J. A., Darveniza, P., Landon, D. N., Land, J. M., Clark, J. B.
<strong>A mitochondrial myopathy with a deficiency of respiratory chain NADH-CoQ reductase activity.</strong>
J. Neurol. Sci. 43: 27-46, 1979.
[PubMed: 521828]
[Full Text: https://doi.org/10.1016/0022-510x(79)90071-6]
</p>
</li>
<li>
<p class="mim-text-font">
Petruzzella, V., Vergari, R., Puzziferri, I., Boffoli, D., Lamantea, E., Zeviani, M., Papa, S.
<strong>A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome.</strong>
Hum. Molec. Genet. 10: 529-535, 2001.
[PubMed: 11181577]
[Full Text: https://doi.org/10.1093/hmg/10.5.529]
</p>
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<li>
<p class="mim-text-font">
Pitkanen, S., Feigenbaum, A., Laframboise, R., Robinson, B. H.
<strong>NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings.</strong>
J. Inherit. Metab. Dis. 19: 675-686, 1996.
[PubMed: 8892026]
[Full Text: https://doi.org/10.1007/BF01799845]
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Procaccio, V., Mousson, B., Beugnot, R., Duborjal, H., Feillet, F., Putet, G., Pignot-Paintrand, I., Lombes, A., De Coo, R., Smeets, H., Lunardi, J., Issartel, J.-P.
<strong>Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts.</strong>
J. Clin. Invest. 104: 83-92, 1999.
[PubMed: 10393702]
[Full Text: https://doi.org/10.1172/JCI6184]
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Robinson, B. H.
<strong>Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect.</strong>
Biochim. Biophys. Acta 1364: 271-286, 1998.
[PubMed: 9593934]
[Full Text: https://doi.org/10.1016/s0005-2728(98)00033-4]
</p>
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Slipetz, D. M., Goodyer, P. R., Rozen, R.
<strong>Congenital deficiency of a 20-kDA subunit of mitochondrial complex I in fibroblasts.</strong>
Am. J. Hum. Genet. 48: 1121-1126, 1991.
[PubMed: 1903590]
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Smeitink, J., van den Heuvel, L.
<strong>Human mitochondrial complex I in health and disease.</strong>
Am. J. Hum. Genet. 64: 1505-1510, 1999.
[PubMed: 10330338]
[Full Text: https://doi.org/10.1086/302432]
</p>
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Soderberg, K., Mascarello, J. T., Bakay, B., Scheffler, I. E.
<strong>Respiration-deficient Chinese hamster cell mutants: genetic characterization.</strong>
Somat. Cell Genet. 5: 225-240, 1979.
[PubMed: 483122]
[Full Text: https://doi.org/10.1007/BF01539163]
</p>
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<li>
<p class="mim-text-font">
Swalwell, H., Kirby, D. M., Blakely, E. L., Mitchell, A., Salemi, R., Sugiana, C., Compton, A. G., Tucker, E. J., Ke, B.-X., Lamont, P. J., Turnbull, D. M., McFarland, R., Taylor, R. W., Thorburn, D. R.
<strong>Respiratory chain complex I deficiency caused by mitochondrial DNA mutations.</strong>
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[PubMed: 21364701]
[Full Text: https://doi.org/10.1038/ejhg.2011.18]
</p>
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Triepels, R. H., van den Heuvel, L. P., Trijbels, J. M., Smeitink, J. A.
<strong>Respiratory chain complex I deficiency.</strong>
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[PubMed: 11579423]
[Full Text: https://doi.org/10.1002/ajmg.1397]
</p>
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van den Heuvel, L., Ruitenbeek, W., Smeets, R., Gelman-Kohan, Z., Elpeleg, O., Loeffen, J., Trijbels, F., Mariman, E., de Bruijn, D., Smeitink, J.
<strong>Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit.</strong>
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[PubMed: 9463323]
[Full Text: https://doi.org/10.1086/301716]
</p>
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von Kleist-Retzow, J.-C., Cormier-Daire, V., de Lonlay, P., Parfait, B., Chretien, D., Rustin, P., Feingold, J., Rotig, A., Munnich, A.
<strong>A high rate (20%-30%) of parental consanguinity in cytochrome-oxidase deficiency.</strong>
Am. J. Hum. Genet. 63: 428-435, 1998.
[PubMed: 9683589]
[Full Text: https://doi.org/10.1086/301957]
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Whitfield, C. D., Bostedor, P., Goodman, D., Haak, M., Chu, E. H. Y.
<strong>Increased hexose transport in Chinese hamster ovary cells resistant to 3-O-methyl-D-glucose.</strong>
J. Biol. Chem. 256: 6651-6656, 1981.
[PubMed: 7240234]
</p>
</li>
<li>
<p class="mim-text-font">
Wijburg, F. A., Barth, P. G., Ruitenbeek, W., Wanders, R. J. A., Vos, G. D., Ploos van Amstel, S. L. B., Schutgens, R. B. H.
<strong>Familial NADH:Q(1) oxidoreductase (complex I) deficiency: variable expression and possible treatment.</strong>
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[PubMed: 2512441]
[Full Text: https://doi.org/10.1007/BF03335419]
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Hilary J. Vernon - updated : 02/12/2021<br>Carol A. Bocchini - updated : 12/13/2018<br>Cassandra L. Kniffin - updated : 11/08/2017<br>Cassandra L. Kniffin - updated : 06/27/2017<br>Cassandra L. Kniffin - updated : 07/26/2016<br>Cassandra L. Kniffin - updated : 9/17/2013<br>Cassandra L. Kniffin - updated : 5/23/2013<br>Cassandra L. Kniffin - updated : 5/1/2013<br>Cassandra L. Kniffin - updated : 2/13/2013<br>Cassandra L. Kniffin - updated : 11/29/2012<br>Cassandra L. Kniffin - updated : 6/12/2012<br>Cassandra L. Kniffin - updated : 2/1/2012<br>Cassandra L. Kniffin - updated : 12/13/2011<br>George E. Tiller - updated : 10/25/2011<br>Cassandra L. Kniffin - updated : 10/12/2011<br>Cassandra L. Kniffin - updated : 11/2/2010<br>Cassandra L. Kniffin - updated : 9/27/2010<br>Cassandra L. Kniffin - updated : 1/25/2010<br>Cassandra L. Kniffin - updated : 10/19/2009<br>Cassandra L. Kniffin - updated : 7/22/2009<br>Cassandra L. Kniffin - updated : 3/23/2009<br>Cassandra L. Kniffin - updated : 10/27/2008<br>Victor A. McKusick - updated : 2/19/2008<br>Cassandra L. Kniffin - updated : 9/10/2007<br>Cassandra L. Kniffin - updated : 11/7/2006<br>Anne M. Stumpf - updated : 11/10/2005<br>Cassandra L. Kniffin - updated : 10/17/2005<br>Cassandra L. Kniffin - reorganized : 9/21/2005<br>Cassandra L. Kniffin - updated : 8/30/2005<br>Cassandra L. Kniffin - updated : 1/5/2005<br>Marla J. F. O&#x27;Neill - updated : 10/14/2004<br>Ada Hamosh - updated : 1/29/2002<br>Victor A. McKusick - updated : 7/24/2001<br>Victor A. McKusick - updated : 2/22/2000<br>Victor A. McKusick - updated : 8/12/1999<br>Victor A. McKusick - updated : 6/18/1999<br>Victor A. McKusick - updated : 5/28/1999<br>Victor A. McKusick - updated : 9/11/1998
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Victor A. McKusick : 9/30/1987
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