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- #277900 - WILSON DISEASE; WND
- OMIM
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<span class="h4">#277900</span>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/277900"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:893" 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/277900" 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://omia.org/OMIA001071/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:893" 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>
</div>
</div>
</div>
<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">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<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:277900" 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> 190823004, 88518009<br />
<strong>ICD10CM:</strong> E83.01<br />
<strong>ORPHA:</strong> 905<br />
<strong>DO:</strong> 893<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>
277900
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
WILSON DISEASE; WND
</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">
WD<br />
HEPATOLENTICULAR DEGENERATION
</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/13/192?start=-3&limit=10&highlight=192">
13q14.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Wilson disease
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/277900"> 277900 </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">
ATP7B
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606882"> 606882 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/277900" 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">
<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/277900" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/277900" 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> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Kayser-Fleischer ring <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/77103006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">77103006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H18.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H18.04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/371.14" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">371.14</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152457&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152457</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200032" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200032</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200032" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200032</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Atypical or prolonged hepatitis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848456</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200122" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200122</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200122" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200122</a>]</span><br /> -
Hepatic cirrhosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/19943007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">19943007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K74.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K74.60</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023890&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023890</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001394</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001394</a>]</span><br /> -
Hepatic coma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/72836002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">72836002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K72.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K72.91</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K76.82" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K76.82</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019147</a>]</span><br /> -
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 /> -
Liver failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59927004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59927004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K72.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K72.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001399" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001399</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001399" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001399</a>]</span><br /> -
High liver copper <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848457&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848457</a>]</span><br /> -
Hepatocellular carcinoma (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109841003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109841003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/187769009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">187769009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1186630006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1186630006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25370001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25370001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C22.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C22.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2239176&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2239176</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001402</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001402</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">
- Esophageal varices <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/28670008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">28670008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I85.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I85.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I85" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I85</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I85.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I85.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0014867&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0014867</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002040" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002040</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002040" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002040</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Renal tubular dysfunction <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95568003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95568003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N25.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N25.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N25" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N25</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151747&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151747</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000124" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000124</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000124" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000124</a>]</span><br /> -
Renal calculi <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95570007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95570007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N20.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N20.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/592.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">592.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392525</a>, <a href="https://bioportal.bioontology.org/search?q=C0022650&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022650</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000787" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000787</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000787" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000787</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Osteoporosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64859006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64859006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Z82.62" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Z82.62</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M81.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M81.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/733.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">733.0</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/V17.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">V17.81</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/733.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">733.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2911643&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2911643</a>, <a href="https://bioportal.bioontology.org/search?q=C0029456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029456</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000939" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000939</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000939" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000939</a>]</span><br /> -
Osteomalacia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4598005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4598005</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/268.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">268.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3887650&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887650</a>, <a href="https://bioportal.bioontology.org/search?q=C0029442&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029442</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002749" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002749</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002749" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002749</a>]</span><br /> -
Chondrocalcinosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/239838005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">239838005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/201637001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">201637001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/239832006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">239832006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M11.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M11.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/712.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">712.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/712.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">712.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/712.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">712.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0553730&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0553730</a>, <a href="https://bioportal.bioontology.org/search?q=C0033802&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033802</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000934" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000934</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000934" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000934</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Osteoarthritis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/225655006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">225655006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/396275006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">396275006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M15-M19" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M15-M19</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M19.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M19.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M19.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M19.90</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/715.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">715.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029408&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029408</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002758" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002758</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002758" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002758</a>]</span><br /> -
Joint hypermobility <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/788453008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">788453008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span><br />
</span>
</div>
</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">
- Tremor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26079004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26079004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R25.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R25.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span><br /> -
Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
Dysphagia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/288939007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">288939007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40739000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40739000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/787.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span><br /> -
Personality changes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/192073007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">192073007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/102943000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">102943000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240735&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240735</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000751" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000751</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000751" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000751</a>]</span><br /> -
Dementia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52448006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52448006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12348006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12348006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F03.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F03.90</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F03</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/290.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">290.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/294.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">294.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">290</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011265&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011265</a>, <a href="https://bioportal.bioontology.org/search?q=C0497327&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0497327</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000726" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000726</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000726" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000726</a>]</span><br /> -
Poor motor coordination <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848453&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848453</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002275" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002275</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002275" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002275</a>]</span><br /> -
Dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
Drooling <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62718007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62718007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013132&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013132</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002307</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0003781" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003781</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002307</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Peripheral Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Mixed demyelinating and axonal polyneuropathy (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4024907&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4024907</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007327" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007327</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007327" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007327</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ENDOCRINE FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hypoparathyroidism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/36976004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">36976004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/E20.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E20.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/252.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">252.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020626&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020626</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000829</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hemolytic anemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61261009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61261009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D55-D59" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D55-D59</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002878&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002878</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001878</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001878</a>]</span><br />
</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">
- Low serum ceruloplasmin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848458&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848458</a>]</span><br /> -
High nonceruloplasmin-bound serum copper <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848459&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848459</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010838" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010838</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010838" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010838</a>]</span><br /> -
High urinary copper <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848460&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848460</a>]</span><br /> -
Proteinuria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29738008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29738008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/231860006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">231860006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R80.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R80.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R80" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R80</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/791.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">791.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1279888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1279888</a>, <a href="https://bioportal.bioontology.org/search?q=C0033687&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033687</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000093</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000093</a>]</span><br /> -
Aminoaciduria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35912001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35912001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238621&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238621</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003355</a>]</span><br /> -
Glycosuria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45154002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45154002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/791.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">791.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0017979&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017979</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003076" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003076</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003076" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003076</a>]</span><br /> -
Uricaciduria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16813005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16813005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0268105&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0268105</a>]</span><br /> -
Hyperphosphaturia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22450000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22450000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85487008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85487008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0268079&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0268079</a>, <a href="https://bioportal.bioontology.org/search?q=C0282201&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0282201</a>, <a href="https://bioportal.bioontology.org/search?q=C0948023&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0948023</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003109" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003109</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003109" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003109</a>]</span><br /> -
Hypercalciuria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71938000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71938000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R82.994" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R82.994</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020438&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020438</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002150" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002150</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002150" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002150</a>]</span><br />
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- Incidence in United States of 1 in 55,000<br /> -
Incidence worldwide of 1 in 30,000 to 50,000<br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the ATPase, Cu++ transporting, beta polypeptide gene (ATP7B, <a href="/entry/606882#0001">606882.0001</a>)<br />
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<p>A number sign (#) is used with this entry because of evidence that Wilson disease (WND) is caused by homozygous or compound heterozygous mutation in the ATP7B gene (<a href="/entry/606882">606882</a>) on chromosome 13q14.</p>
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<strong>Description</strong>
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<p>Wilson disease (WND) is an autosomal recessive disorder characterized by dramatic build-up of intracellular hepatic copper with subsequent hepatic and neurologic abnormalities.</p><p><a href="#28" class="mim-tip-reference" title="De Bie, P., Muller, P., Wijmenga, C., Klomp, L. W. J. &lt;strong&gt;Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes.&lt;/strong&gt; J. Med. Genet. 44: 673-688, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17717039/&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;17717039&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17717039[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/10.1136/jmg.2007.052746&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="17717039">De Bie et al. (2007)</a> provided a detailed review of the molecular pathogenesis of Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17717039" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In Wilson disease, the basal ganglia and liver undergo changes that express themselves in neurologic manifestations and signs of cirrhosis, respectively. A disturbance in copper metabolism is somehow involved in the mechanism. Low ceruloplasmin (<a href="/entry/117700">117700</a>) is found in the serum. <a href="#96" class="mim-tip-reference" title="Shokeir, M. H. K., Shreffler, D. C. &lt;strong&gt;Cytochrome oxidase deficiency in Wilson&#x27;s disease: a suggested ceruloplasmin function.&lt;/strong&gt; Proc. Nat. Acad. Sci. 62: 867-872, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4308098/&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;4308098&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.62.3.867&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="4308098">Shokeir and Shreffler (1969)</a> advanced the hypothesis that ceruloplasmin functions in enzymatic transfer of copper to copper-containing enzymes such as cytochrome oxidase. Supporting the hypothesis was the finding of markedly reduced levels of activity of cytochrome oxidase in Wilson disease and moderate reductions in heterozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4308098" 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>The Kayser-Fleischer ring is a deep copper-colored ring at the periphery of the cornea which is frequently found in Wilson disease and is thought to represent copper deposits. <a href="#4" class="mim-tip-reference" title="Bearn, A. G., McKusick, V. A. &lt;strong&gt;Azure lunulae: an unusual change in the fingernails in two patients with hepatolenticular degeneration (Wilson&#x27;s disease).&lt;/strong&gt; J. Am. Med. Assoc. 166: 904-906, 1958.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13502081/&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;13502081&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/jama.1958.62990080001010&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="13502081">Bearn and McKusick (1958)</a> and <a href="#120" class="mim-tip-reference" title="Whelton, M. J., Pope, F. M. &lt;strong&gt;Azure lunules in argyria: corneal changes resembling Kayser-Fleischer rings.&lt;/strong&gt; Arch. Intern. Med. 121: 267-269, 1968.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5642746/&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;5642746&lt;/a&gt;]" pmid="5642746">Whelton and Pope (1968)</a> described azure lunulae of the fingernails in patients with Wilson disease. These are presumably of the same significance as the Kayser-Fleischer ring and possibly arise by the same mechanism. Hypercalciuria and nephrocalcinosis are not uncommon in patients with Wilson disease. Hypercalciuria associated with this disorder was first reported by <a href="#75" class="mim-tip-reference" title="Litin, R. B., Randall, R. V., Goldstein, N. P., Power, M. H., Diessner, G. R. &lt;strong&gt;Hypercalciuria in hepatolenticular degeneration (Wilson&#x27;s disease).&lt;/strong&gt; Am. J. Med. Sci. 238: 614-620, 1959.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14417517/&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;14417517&lt;/a&gt;]" pmid="14417517">Litin et al. (1959)</a>. <a href="#121" class="mim-tip-reference" title="Wiebers, D. O., Wilson, D. M., McLeod, R. A., Goldstein, N. P. &lt;strong&gt;Renal stones in Wilson&#x27;s disease.&lt;/strong&gt; Am. J. Med. 67: 249-254, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/463930/&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;463930&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9343(79)90399-1&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="463930">Wiebers et al. (1979)</a> observed renal stones in 7 of 54 patients with Wilson disease. Penicillamine therapy was accompanied by a decrease in urinary calcium excretion to normal values in 3 patients, but hypercalciuria persisted in 3. <a href="#3" class="mim-tip-reference" title="Azizi, E., Eshel, G., Aladjem, M. &lt;strong&gt;Hypercalciuria and nephrolithiasis as a presenting sign in Wilson disease.&lt;/strong&gt; Europ. J. Pediat. 148: 548-549, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2744017/&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;2744017&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00441555&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="2744017">Azizi et al. (1989)</a> described hypercalciuria and nephrolithiasis as presenting signs in Wilson disease and postulated tubular defect in calcium reabsorption. <a href="#59" class="mim-tip-reference" title="Hoppe, B., Neuhaus, T., Superti-Furga, A., Forster, I., Leumann, E. &lt;strong&gt;Hypercalciuria and nephrocalcinosis, a feature of Wilson&#x27;s disease.&lt;/strong&gt; Nephron 65: 460-462, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8290000/&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;8290000&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1159/000187530&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="8290000">Hoppe et al. (1993)</a> described a 17-year-old male with a 6-year history of hypercalciuria, nephrocalcinosis, and nephrolithiasis, in whom Wilson disease was finally diagnosed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8290000+14417517+2744017+5642746+13502081+463930" 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="Bearn, A. G. &lt;strong&gt;A genetical analysis of thirty families with Wilson&#x27;s disease (hepatolenticular degeneration).&lt;/strong&gt; Ann. Hum. Genet. 24: 33-43, 1960.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13797909/&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;13797909&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1469-1809.1959.tb01713.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="13797909">Bearn (1960)</a> suggested that Jewish WND patients from eastern Europe are different from other groups of patients in that the age at onset is later, the disease is generally milder, and the serum copper and serum ceruloplasmin levels are 'particularly liable to be of normal concentration.' <a href="#9" class="mim-tip-reference" title="Bonne-Tamir, B., Frydman, M., Agger, M. S., Bekeer, R., Bowcock, A. M., Hebert, J. M., Cavalli-Sforza, L. L., Farrer, L. A. &lt;strong&gt;Wilson&#x27;s disease in Israel: a genetic and epidemiological study.&lt;/strong&gt; Ann. Hum. Genet. 54: 155-168, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2382969/&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;2382969&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1469-1809.1990.tb00372.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="2382969">Bonne-Tamir et al. (1990)</a> provided a full analysis of Wilson disease in Israel. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13797909+2382969" 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>From a study of 28 Canadian families, <a href="#23" class="mim-tip-reference" title="Cox, D. W., Fraser, F. C., Sass-Kortsak, A. &lt;strong&gt;A genetic study of Wilson&#x27;s disease: evidence for heterogeneity.&lt;/strong&gt; Am. J. Hum. Genet. 24: 646-666, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5082916/&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;5082916&lt;/a&gt;]" pmid="5082916">Cox et al. (1972)</a> suggested that there are at least 3 forms of Wilson disease. In a rare 'atypical form,' the heterozygotes show about 50% of the normal level of ceruloplasmin. This gene may have been of German-Mennonite derivation. In the 2 typical forms heterozygotes have normal ceruloplasmin levels, although they can be identified by decreased reappearance of radioactive copper into serum and ceruloplasmin. The authors referred to the 2 'typical forms' as the Slavic and the juvenile type. The Slavic type has a late age of onset and is predominantly a neurologic disease. The juvenile type, which occurs in western Europeans and several other ethnic groups, has onset before age 16 years and is frequently a hepatic disease. <a href="#25" class="mim-tip-reference" title="Czaja, M. J., Weiner, F. R., Schwarzenberg, S. J., Sternlieb, I., Scheinberg, I. H., Van Thiel, D. H., LaRusso, N. F., Giambrone, M.-A., Kirschner, R., Koschinsky, M. L., MacGillivray, R. T. A., Zern, M. A. &lt;strong&gt;Molecular studies of ceruloplasmin deficiency in Wilson&#x27;s disease.&lt;/strong&gt; J. Clin. Invest. 80: 1200-1204, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3654978/&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;3654978&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI113180&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="3654978">Czaja et al. (1987)</a> demonstrated reduced ceruloplasmin gene transcription in 4 patients with Wilson disease (44% of controls). Low levels of ceruloplasmin are a normal finding in the newborn (<a href="#97" class="mim-tip-reference" title="Shokeir, M. H. K. &lt;strong&gt;Investigations on the nature of ceruloplasmin deficiency in the newborn.&lt;/strong&gt; Clin. Genet. 2: 223-227, 1971.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5004412/&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;5004412&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1971.tb00281.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="5004412">Shokeir, 1971</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5082916+3654978+5004412" 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 Israel, <a href="#88" class="mim-tip-reference" title="Passwell, J., Adam, A., Garfinkel, D., Streiffler, M., Cohen, B. E. &lt;strong&gt;Heterogeneity of Wilson&#x27;s disease in Israel.&lt;/strong&gt; Isr. J. Med. Sci. 13: 15-19, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/838566/&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;838566&lt;/a&gt;]" pmid="838566">Passwell et al. (1977)</a> observed that Arab patients show an earlier age of onset and more severe course than Jewish patients. Within families of both ethnic groups, age of onset and type of disease show a close correlation. Thus, the authors concluded that the interethnic differences may reflect different mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=838566" 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="#38" class="mim-tip-reference" title="Fitzgerald, M. A., Gross, J. B., Goldstein, N. P., Wahner, H. W., McCall, J. T. &lt;strong&gt;Wilson&#x27;s disease (hepatolenticular degeneration) of late adult onset: report of a case.&lt;/strong&gt; Mayo Clin. Proc. 50: 438-442, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1152537/&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;1152537&lt;/a&gt;]" pmid="1152537">Fitzgerald et al. (1975)</a> described a 57-year-old man with liver disease that they concluded represented Wilson disease. <a href="#91" class="mim-tip-reference" title="Ross, M. E., Jacobson, I. M., Dienstag, J. L., Martin, J. B. &lt;strong&gt;Late-onset Wilson&#x27;s disease with neurological involvement in the absence of Kayser-Fleischer rings.&lt;/strong&gt; Ann. Neurol. 17: 411-413, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4004163/&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;4004163&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410170421&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="4004163">Ross et al. (1985)</a> described a patient who was found to have hepatosplenomegaly at age 51, developed hand tremor at 52, and was having difficulty with hand dexterity at 55. The diagnosis of Wilson disease was made at age 58 on the basis of urinary, serum, and hepatic copper studies and liver histology, and despite the absence of Kayser-Fleischer rings. Wilson disease is not generally considered in patients over 30 years of age who present with liver disease and without neurologic signs. <a href="#27" class="mim-tip-reference" title="Danks, D. M., Metz, G., Sewell, R., Prewett, E. J. &lt;strong&gt;Wilson&#x27;s disease in adults with cirrhosis but no neurological abnormalities.&lt;/strong&gt; Brit. Med. J. 301: 331-332, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2393743/&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;2393743&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/bmj.301.6747.331&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="2393743">Danks et al. (1990)</a> reported 4 such cases: 2 men, aged 43 and 48, and 2 women, aged 44 and 58. The 58-year-old woman had been ill for only 1 week and died in 36 hours of acute hepatorenal failure. Her sister had died of cirrhosis and liver failure at age 28. Alcohol intake was minimal or completely avoided in all. None of the known hepatitis viruses could be identified and no autoantibodies were detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1152537+2393743+4004163" 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="#66" class="mim-tip-reference" title="Kuan, P. &lt;strong&gt;Cardiac Wilson&#x27;s disease.&lt;/strong&gt; Chest 91: 579-583, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3829752/&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;3829752&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1378/chest.91.4.579&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="3829752">Kuan (1987)</a> demonstrated manifestations of myocardial involvement in Wilson disease. The occurrence of chondrocalcinosis and osteoarthritis in Wilson disease may be due to copper accumulation similar to the arthropathy of hemochromatosis (HFE; <a href="/entry/235200">235200</a>) (<a href="#82" class="mim-tip-reference" title="Menerey, K. A., Eider, W., Brewer, G. J., Braunstein, E. M., Schumacher, H. R., Fox, I. H. &lt;strong&gt;The arthropathy of Wilson&#x27;s disease: clinical and pathologic features.&lt;/strong&gt; J. Rheum. 15: 331-337, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3361541/&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;3361541&lt;/a&gt;]" pmid="3361541">Menerey et al., 1988</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3361541+3829752" 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="#100" class="mim-tip-reference" title="Starosta-Rubinstein, S., Young, A. B., Kluin, K., Hill, G., Aisen, A. M., Gabrielsen, T., Brewer, G. J. &lt;strong&gt;Clinical assessment of 31 patients with Wilson&#x27;s disease: correlations with structural changes on magnetic resonance imaging.&lt;/strong&gt; Arch. Neurol. 44: 365-370, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3827691/&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;3827691&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1987.00520160007005&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="3827691">Starosta-Rubinstein et al. (1987)</a> correlated clinical manifestations with the findings of magnetic resonance imaging (MRI) of the brain. <a href="#112" class="mim-tip-reference" title="van Wassenaer-van Hall, H. N., van den Heuvel, A. G., Jansen, G. H., Hoogenraad, T. U., Mali, W. P. T. M. &lt;strong&gt;Cranial MR in Wilson disease: abnormal white matter in extrapyramidal and pyramidal tracts.&lt;/strong&gt; Am. J. Neuroradiol. 16: 2021-2027, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8585490/&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;8585490&lt;/a&gt;]" pmid="8585490">Van Wassenaer-van Hall et al. (1995)</a> also used cranial MRI to study WND patients. Although the most striking findings on their MRI scan were abnormalities of the basal ganglia in generalized cerebral atrophy, they also noted subtle white matter abnormalities in some WND patients, particularly at the dentatorubrothalamic, pontocerebellar, and corticospinal tracts. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8585490+3827691" 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>From Slovenia, <a href="#34" class="mim-tip-reference" title="Ferlan-Marolt, V., Stepec, S. &lt;strong&gt;Fulminant Wilsonian hepatitis unmasked by disease progression: report of a case and review of the literature.&lt;/strong&gt; Dig. Dis. Sci. 44: 1054-1058, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10235618/&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;10235618&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1026637403894&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="10235618">Ferlan-Marolt and Stepec (1999)</a> reported a 24-year-old woman with fulminant Wilsonian hepatitis accompanied by hemolytic anemia and leading to death in a few weeks. Kayser-Fleischer rings were said to have been absent, and there were no neurologic abnormalities until the development of the flapping tremor of hepatic failure in the last days of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10235618" 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="#49" class="mim-tip-reference" title="Gu, M., Cooper, J. M., Butler, P., Walker, A. P., Mistry, P. K., Dooley, J. S., Schapira, A. H. V. &lt;strong&gt;Oxidative-phosphorylation defects in liver of patients with Wilson&#x27;s disease.&lt;/strong&gt; Lancet 356: 469-474, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10981891/&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;10981891&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(00)02556-3&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="10981891">Gu et al. (2000)</a> studied mitochondrial function and aconitase activity in Wilson disease liver tissue and compared the results with those in a series of healthy controls and patients without Wilson disease. There was evidence of severe mitochondrial dysfunction in the livers of patients with Wilson disease. Enzyme activities were decreased as follows: complex I by 62%, complex II+III by 52%, complex IV by 33%, and aconitase by 71%. These defects did not seem to be secondary to penicillamine use, cholestasis, or poor hepatocellular synthetic function. <a href="#49" class="mim-tip-reference" title="Gu, M., Cooper, J. M., Butler, P., Walker, A. P., Mistry, P. K., Dooley, J. S., Schapira, A. H. V. &lt;strong&gt;Oxidative-phosphorylation defects in liver of patients with Wilson&#x27;s disease.&lt;/strong&gt; Lancet 356: 469-474, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10981891/&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;10981891&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(00)02556-3&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="10981891">Gu et al. (2000)</a> stated that the pattern of enzyme defects suggests that free radical formation and oxidative damage, probably mediated via mitochondrial copper accumulation, are important in Wilson disease pathogenesis, and that their results provide a rationale for a study of the use of antioxidants in Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10981891" 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>Both Wilson disease and hemochromatosis (<a href="/entry/235200">235200</a>), characterized by excess hepatic deposition of iron and copper, respectively, produce oxidative stress and increase the risk of liver cancer. Because the frequency of p53 mutated alleles (<a href="/entry/191170">191170</a>) in nontumorous human tissue may be a biomarker of oxyradical damage and identify individuals at increased cancer risk, <a href="#62" class="mim-tip-reference" title="Hussain, S. P., Raja, K., Amstad, P. A., Sawyer, M., Trudel, L. J., Wogan, G. N., Hofseth, L. J., Shields, P. G., Billiar, T. R., Trautwein, C., Hohler, T., Galle, P. R., Phillips, D. H., Markin, R., Marrogi, A. J., Harris, C. C. &lt;strong&gt;Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: oxyradical overload diseases.&lt;/strong&gt; Proc. Nat. Acad. Sci. 97: 12770-12775, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11050162/&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;11050162&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11050162[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/10.1073/pnas.220416097&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="11050162">Hussain et al. (2000)</a> determined the frequency of p53 mutated alleles in nontumorous liver tissue from WND and hemochromatosis patients. When compared with the liver samples from normal controls, higher frequencies of G:C to T:A transversions at codon 249, and C:G to A:T transversions and C:G to T:A transitions at codon 250 were found in liver tissue from WND cases, and a higher frequency of G:C to T:A transversions at codon 249 was also found in liver tissue from hemochromatosis cases. Sixty percent of WND and 28% of hemochromatosis cases also showed a higher expression of inducible nitric oxide synthase in the liver, which suggested nitric oxide as a source of increased oxidative stress. The results were consistent with the hypothesis that the generation of oxygen/nitrogen species and unsaturated aldehydes from iron and copper overload in hemochromatosis and WND causes mutation in the p53 tumor suppressor gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11050162" 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="#54" class="mim-tip-reference" title="Hedera, P., Brewer, G. J., Fink, J. K. &lt;strong&gt;White matter changes in Wilson disease. (Letter)&lt;/strong&gt; Arch. Neurol. 59: 866-867, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12020274/&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;12020274&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.59.5.866&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="12020274">Hedera et al. (2002)</a> reported a 13-year-old male with Wilson disease who exhibited leukoencephalopathy early in the disease course. MRI showed increased signal intensities in the basal ganglia and throughout the subcortical white matter in the frontal lobes, which later extended to the parietal and occipital lobes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12020274" 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="#103" class="mim-tip-reference" title="Takeshita, Y., Shimizu, N., Yamaguchi, Y., Nakazono, H., Saitou, M., Fujikawa, Y., Aoki, T. &lt;strong&gt;Two families with Wilson disease in which siblings showed different phenotypes.&lt;/strong&gt; J. Hum. Genet. 47: 543-547, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12376745/&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;12376745&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s100380200082&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="12376745">Takeshita et al. (2002)</a> investigated 2 families with Wilson disease in which sibs showed different clinical phenotypes and different ages at onset. In the first family, the second and fourth male children demonstrated onset of the neurologic type of Wilson disease at 16 and 28 years of age, respectively, and the first female child developed the hepatic type at 38 years of age. In family 2, the second male child showed neurologic symptoms at 32 years of age and was diagnosed as having the hepatoneurologic type of Wilson disease; the 35-year-old first female child was found to have the hepatic type in familial screening. In both families, affected individuals were compound heterozygotes for mutations in the ATP7B gene. In the first family, the mutations were R778L (<a href="/entry/606882#0009">606882.0009</a>) and R919G (<a href="/entry/606882#0014">606882.0014</a>). In the second family, the mutations were 2511delA (<a href="/entry/606882#0015">606882.0015</a>) and A874V (<a href="/entry/606882#0016">606882.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376745" 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="#55" class="mim-tip-reference" title="Hlubocka, Z., Marecek, Z., Linhart, A., Kejrova, E., Pospisilova, L., Martasek, P., Aschermann, M. &lt;strong&gt;Cardiac involvement in Wilson disease.&lt;/strong&gt; J. Inherit. Metab. Dis. 25: 269-277, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12227457/&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;12227457&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1016546223327&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="12227457">Hlubocka et al. (2002)</a> studied 42 patients with Wilson disease (19 men and 23 women, mean age 34 +/- 10 years) and 42 age- and sex-matched healthy volunteers. All subjects underwent complete echocardiographic examination; 24-hour Holter monitoring was performed in 23 Wilson disease patients. In comparison with healthy subjects, patients with Wilson disease had increased thickness of the interventricular septum and left ventricular (LV) posterior wall. While the 2 groups did not differ in LV mass index, relative LV wall thickness was significantly increased in the Wilson disease patients compared to control subjects. Concentric LV remodeling was present in 9 patients (21%) and LV hypertrophy in 1 patient. Diastolic filling and the frequency of valvular abnormalities were comparable in both groups. Twenty-four-hour Holter monitoring detected ECG abnormalities in 10 patients (42%), the most frequent findings being runs of supraventricular tachycardias and frequent supraventricular ectopic beats. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12227457" 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="#63" class="mim-tip-reference" title="Jung, K.-H., Ahn, T.-B., Jeon, B. S. &lt;strong&gt;Wilson disease with an initial manifestation of polyneuropathy.&lt;/strong&gt; Arch. Neurol. 62: 1628-1631, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16216950/&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;16216950&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.62.10.1628&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="16216950">Jung et al. (2005)</a> reported a 17-year-old Korean man with Wilson disease who presented with polyneuropathy at least 6 months before developing more typical symptoms. Initial symptoms included intermittent paresthesia and weakness in both hands and feet with normal sensory examination. Nerve conduction studies and sural nerve biopsy were consistent with a mixed demyelinating and axonal neuropathy. Treatment with penicillamine, zinc sulfate, and vitamin B6 resulted in clinical improvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16216950" 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="diagnosis" class="mim-anchor"></a>
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<strong>Diagnosis</strong>
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<p><a href="#21" class="mim-tip-reference" title="Chowrimootoo, G. F. E., Scowcroft, H., Seymour, C. A. &lt;strong&gt;Caeruloplasmin isoforms in Wilson&#x27;s disease in neonates.&lt;/strong&gt; Arch. Dis. Child. Fetal Neonatal Ed. 79: F198-F201, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10194991/&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;10194991&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/fn.79.3.f198&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="10194991">Chowrimootoo et al. (1998)</a> investigated the neonatal diagnosis of Wilson disease by measuring ceruloplasmin isoforms in neonatal cord blood samples and venous blood from both healthy adults and patients with Wilson disease. Total ceruloplasmin levels were reduced in all neonatal specimens. The plasma isoform, however, was significantly reduced or absent only in patients with Wilson disease, whereas the biliary isoform was reduced both in healthy neonates and patients with Wilson disease. The authors commented that measurement of ceruloplasmin isoforms in cord blood or dried blood spots may permit neonatal diagnosis of this condition, before substantial tissue damage has occurred. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10194991" 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="#47" class="mim-tip-reference" title="Gow, P. J., Smallwood, R. A., Angus, P. W., Smith, A. L., Wall, A. J., Sewell, R. B. &lt;strong&gt;Diagnosis of Wilson&#x27;s disease: an experience over three decades.&lt;/strong&gt; Gut 46: 415-419, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10673307/&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;10673307&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/gut.46.3.415&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="10673307">Gow et al. (2000)</a> reported their detailed experience of 30 patients with a diagnosis of Wilson disease seen in 2 Australian centers between 1971 and 1998. Twenty-two patients presented with chronic disease; age at diagnosis ranged from 7 to 58 years. Only 14 of these patients (64%) had Kayser-Fleischer rings; 5 of these had low serum ceruloplasmin concentrations and normal urinary copper excretion, 2 had normal ceruloplasmin levels and high urinary copper excretion, and 7 had the classic combination of low serum ceruloplasmin and high urinary copper. Eight patients presented with fulminant hepatic failure, with age at diagnosis ranging from 11 to 54 years; only 6 of these had Kayser-Fleischer rings, 7 had low serum ceruloplasmin, and 4 of them had raised urinary copper excretion. The others were anuric. Examination of the livers of these 8 patients, either at autopsy or posttransplantation, showed cirrhosis and elevated copper content. <a href="#47" class="mim-tip-reference" title="Gow, P. J., Smallwood, R. A., Angus, P. W., Smith, A. L., Wall, A. J., Sewell, R. B. &lt;strong&gt;Diagnosis of Wilson&#x27;s disease: an experience over three decades.&lt;/strong&gt; Gut 46: 415-419, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10673307/&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;10673307&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/gut.46.3.415&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="10673307">Gow et al. (2000)</a> commented that the diagnosis of Wilson disease depended on the evaluation of clinical and laboratory evidence of abnormal copper metabolism, but that no single feature was reliable in isolation. Further, the authors suggested that Wilson disease should be considered in any patient at any age presenting with unusual liver or neurologic abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10673307" 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="Firneisz, G., Woller, J., Ferenci, P., Szalay, F. &lt;strong&gt;Postcremation diagnosis from an electric shaver.&lt;/strong&gt; Lancet 358: 34 only, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11454376/&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;11454376&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(00)05254-5&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="11454376">Firneisz et al. (2001)</a> described postmortem (postcremation) diagnosis of Wilson disease on the basis of skin cells left on the deceased's electric shaver. <a href="#40" class="mim-tip-reference" title="Foye, P. M. &lt;strong&gt;Postcremation diagnosis. (Letter)&lt;/strong&gt; Lancet 358: 1554 only, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11705608/&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;11705608&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(01)06609-0&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="11705608">Foye (2001)</a> and <a href="#68" class="mim-tip-reference" title="Kuruvilla, A. &lt;strong&gt;Postcremation diagnosis. (Letter)&lt;/strong&gt; Lancet 358: 1554 only, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11705607/&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;11705607&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(01)06610-7&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="11705607">Kuruvilla (2001)</a> took these authors to task, noting that the man's DNA added no new information since the same mutation was identified in the man's father and 2 children. <a href="#40" class="mim-tip-reference" title="Foye, P. M. &lt;strong&gt;Postcremation diagnosis. (Letter)&lt;/strong&gt; Lancet 358: 1554 only, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11705608/&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;11705608&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(01)06609-0&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="11705608">Foye (2001)</a> commented that with the growing array of available tests, 'we must always remember in each individual case to stop first and ask not just whether a particular test could be done, but whether it should be done.' <a href="#68" class="mim-tip-reference" title="Kuruvilla, A. &lt;strong&gt;Postcremation diagnosis. (Letter)&lt;/strong&gt; Lancet 358: 1554 only, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11705607/&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;11705607&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(01)06610-7&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="11705607">Kuruvilla (2001)</a> noted that the man had movement disorder for at least 10 years before his death and presented to his physician with parkinsonian symptoms and florid manifestations of cirrhosis. Because Kayser-Fleischer ring is present in 100% of patients with CNS manifestations of Wilson disease, neuroophthalmologic slit-lamp assessment is mandatory and cost effective in all patients suspected of having this disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11705608+11454376+11705607" 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="#33" class="mim-tip-reference" title="Ferenci, P. &lt;strong&gt;Regional distribution of mutations in the ATP7B gene in patients with Wilson disease: impact on genetic testing.&lt;/strong&gt; Hum. Genet. 120: 151-159, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16791614/&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;16791614&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-006-0202-5&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="16791614">Ferenci (2006)</a> reviewed the geographic distribution of mutations in the ATP7B gene in Wilson disease patients to improve genetic diagnosis of Wilson disease. The most common mutation in patients from Europe is H1069Q (<a href="/entry/606882#0006">606882.0006</a>). A unique 15-bp deletion in the 5-prime region (<a href="/entry/606882#0010">606882.0010</a>) is frequent in Sardinia. M645R (<a href="/entry/606882#0020">606882.0020</a>) is common in Spain, and R778L (<a href="/entry/606882#0009">606882.0009</a>) is often found in patients from eastern Asia. <a href="#33" class="mim-tip-reference" title="Ferenci, P. &lt;strong&gt;Regional distribution of mutations in the ATP7B gene in patients with Wilson disease: impact on genetic testing.&lt;/strong&gt; Hum. Genet. 120: 151-159, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16791614/&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;16791614&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-006-0202-5&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="16791614">Ferenci (2006)</a> also presented a clinical algorithm for the diagnosis of Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16791614" 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>Prenatal Diagnosis</em></strong></p><p>
<a href="#22" class="mim-tip-reference" title="Cossu, P., Pirastu, M., Nucaro, A., Figus, A., Balestrieri, A., Borrone, C., Giacchino, R., Devoto, M., Monni, G., Cao, A. &lt;strong&gt;Prenatal diagnosis of Wilson&#x27;s disease by analysis of DNA polymorphism. (Letter)&lt;/strong&gt; New Eng. J. Med. 327: 57, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1350853/&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;1350853&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199207023270116&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="1350853">Cossu et al. (1992)</a> demonstrated how one can use flanking markers to do prenatal diagnosis by the linkage principle in this disorder. The probability of the fetus being affected was estimated to be only 0.007 in the example given. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1350853" 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="clinicalManagement" class="mim-anchor"></a>
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<strong>Clinical Management</strong>
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<p><a href="#99" class="mim-tip-reference" title="Sokol, R. J., Francis, P. D., Gold, S. H., Ford, D. M., Lum, G. M., Ambruso, D. R. &lt;strong&gt;Orthotopic liver transplantation for acute fulminant Wilson disease.&lt;/strong&gt; J. Pediat. 107: 549-552, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3900322/&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;3900322&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(85)80016-0&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="3900322">Sokol et al. (1985)</a> successfully treated a 13-year-old girl with fulminant Wilson disease with orthotopic liver transplant. <a href="#90" class="mim-tip-reference" title="Polson, R. J., Rolles, K., Calne, R. Y., Williams, R., Marsden, D. &lt;strong&gt;Reversal of severe neurological manifestations of Wilson&#x27;s disease following orthotopic liver transplantation.&lt;/strong&gt; Quart. J. Med. 64: 685-691, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3328213/&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;3328213&lt;/a&gt;]" pmid="3328213">Polson et al. (1987)</a> reported dramatic improvement in neurologic function over a period of 3 or 4 months after orthotopic liver transplantation. However, <a href="#50" class="mim-tip-reference" title="Guarino, M., Stracciari, A., D&#x27;Alessandro, R., Pazzaglia, P. &lt;strong&gt;No neurological improvement after liver transplantation for Wilson&#x27;s disease.&lt;/strong&gt; Acta Neurol. Scand. 92: 405-408, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8610495/&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;8610495&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1600-0404.1995.tb00155.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="8610495">Guarino et al. (1995)</a> published a case of a man treated with orthotopic liver transplantation who developed postoperative central pontine and extrapontine myelinolysis and then went on to develop new extrapyramidal symptoms 19 months after the liver transplant. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8610495+3328213+3900322" 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="#74" class="mim-tip-reference" title="Lingam, S., Wilson, J., Nazer, H., Mowat, A. P. &lt;strong&gt;Neurological abnormalities in Wilson&#x27;s disease are reversible.&lt;/strong&gt; Neuropediatrics 18: 11-12, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3561699/&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;3561699&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1055/s-2008-1052427&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="3561699">Lingam et al. (1987)</a> showed that neurologic abnormalities can be reversed to some extent in children with Wilson disease. In some patients it was necessary to substitute triethylene tetramine (TETA) for penicillamine because of adverse effects of the latter agent. Wilson disease is effectively treated by any 1 of 3 drugs, D-penicillamine, trien, or zinc acetate (<a href="#15" class="mim-tip-reference" title="Brewer, G. J., Yuzbasiyan-Gurkan, V., Young, A. B. &lt;strong&gt;The treatment of Wilson&#x27;s disease.&lt;/strong&gt; Semin. Neurol. 7: 209-220, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3332455/&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;3332455&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1055/s-2008-1041420&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="3332455">Brewer et al., 1987</a>). <a href="#13" class="mim-tip-reference" title="Brewer, G. J., Dick, R. D., Yuzbasiyan-Gurkan, V., Johnson, V., Wang, Y. &lt;strong&gt;Treatment of Wilson&#x27;s disease with zinc XIII: therapy with zinc in presymptomatic patients from the time of diagnosis.&lt;/strong&gt; J. Lab. Clin. Med. 123: 849-858, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8201263/&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;8201263&lt;/a&gt;]" pmid="8201263">Brewer et al. (1994)</a> described the successful treatment with zinc acetate of 13 presymptomatic patients identified through screening of sibs. The levels of hepatic copper in response to several years of zinc therapy may remain the same, go down, or go up temporarily. This is a reflection of zinc induction of hepatic metallothionein, which sequesters copper in a nontoxic pool. Hepatic copper levels should not be used to manage therapy. Liver function is well preserved by zinc therapy, and <a href="#13" class="mim-tip-reference" title="Brewer, G. J., Dick, R. D., Yuzbasiyan-Gurkan, V., Johnson, V., Wang, Y. &lt;strong&gt;Treatment of Wilson&#x27;s disease with zinc XIII: therapy with zinc in presymptomatic patients from the time of diagnosis.&lt;/strong&gt; J. Lab. Clin. Med. 123: 849-858, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8201263/&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;8201263&lt;/a&gt;]" pmid="8201263">Brewer et al. (1994)</a> observed no zinc toxicity in these 13 patients. <a href="#13" class="mim-tip-reference" title="Brewer, G. J., Dick, R. D., Yuzbasiyan-Gurkan, V., Johnson, V., Wang, Y. &lt;strong&gt;Treatment of Wilson&#x27;s disease with zinc XIII: therapy with zinc in presymptomatic patients from the time of diagnosis.&lt;/strong&gt; J. Lab. Clin. Med. 123: 849-858, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8201263/&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;8201263&lt;/a&gt;]" pmid="8201263">Brewer et al. (1994)</a> reported that no patient developed symptoms related to Wilson disease. However, <a href="#69" class="mim-tip-reference" title="Lang, C. J. G., Rabas-Kolominsky, P., Engelhardt, A., Kobras, G., Konig, H. J. &lt;strong&gt;Fatal deterioration of Wilson&#x27;s disease after institution of oral zinc therapy. (Letter)&lt;/strong&gt; Arch. Neurol. 50: 1007-1008, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8280286/&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;8280286&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1993.00540100008005&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="8280286">Lang et al. (1993)</a> reported a 30-year-old patient who deteriorated at the end of the first month of zinc therapy and died in hepatic coma. <a href="#58" class="mim-tip-reference" title="Hoogenraad, T. U. &lt;strong&gt;Dangers of interrupting decoppering treatment in Wilson&#x27;s disease. (Letter)&lt;/strong&gt; Arch. Neurol. 51: 972-973, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7945006/&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;7945006&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1994.00540220018005&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="7945006">Hoogenraad (1994)</a> expressed doubt that zinc played a causal role in the worsening condition of the patient reported by <a href="#69" class="mim-tip-reference" title="Lang, C. J. G., Rabas-Kolominsky, P., Engelhardt, A., Kobras, G., Konig, H. J. &lt;strong&gt;Fatal deterioration of Wilson&#x27;s disease after institution of oral zinc therapy. (Letter)&lt;/strong&gt; Arch. Neurol. 50: 1007-1008, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8280286/&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;8280286&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1993.00540100008005&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="8280286">Lang et al. (1993)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3561699+3332455+8280286+8201263+7945006" 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="Devesa, R., Alvarez, A., de las Heras, G., de Miguel, J. R. &lt;strong&gt;Wilson&#x27;s disease treated with trientine during pregnancy.&lt;/strong&gt; J. Pediat. Gastroent. Nutr. 20: 102-103, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7884606/&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;7884606&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00005176-199501000-00018&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="7884606">Devesa et al. (1995)</a> described an uneventful pregnancy with delivery of a healthy newborn in a woman with Wilson disease who had been on the oral copper-chelating agent trientine (triethylenetetramine dihydrochloride) because of the development of nephrosis when D-penicillamine was used. <a href="#53" class="mim-tip-reference" title="Hartard, C., Kunze, K. &lt;strong&gt;Pregnancy in a patient with Wilson&#x27;s disease treated with D-penicillamine and zinc sulfate: a case report and review of the literature.&lt;/strong&gt; Europ. Neurol. 34: 337-340, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7851456/&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;7851456&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1159/000117074&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="7851456">Hartard and Kunze (1994)</a> reported a successful pregnancy in a patient with Wilson disease treated with D-penicillamine and zinc sulfate 3 years prior to and during the pregnancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7884606+7851456" 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="#12" class="mim-tip-reference" title="Brewer, G. J., Dick, R. D., Johnson, V. D., Brunberg, J. A., Kluin, K. J., Fink, J. K. &lt;strong&gt;Treatment of Wilson&#x27;s disease with zinc. XV. Long-term follow-up studies.&lt;/strong&gt; J. Lab. Clin. Med. 132: 264-278, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9794697/&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;9794697&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-2143(98)90039-7&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="9794697">Brewer et al. (1998)</a> presented data on the long-term follow-up of maintenance zinc treatment of 141 symptomatic and presymptomatic patients with Wilson disease. From these data, they concluded that zinc is effective as a sole therapy and that it has low toxicity. The authors also presented limited data on zinc treatment of children and pregnant women with Wilson disease which were also suggestive of efficacy and low toxicity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9794697" 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="#72" class="mim-tip-reference" title="LeWitt, P. A. &lt;strong&gt;Penicillamine as a controversial treatment for Wilson&#x27;s disease. (Editorial)&lt;/strong&gt; Mov. Disord. 14: 555-556, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10435491/&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;10435491&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/1531-8257(199907)14:4&lt;555::aid-mds1003&gt;3.0.co;2-l&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="10435491">LeWitt (1999)</a> observed that 'Whereas management of Wilson's disease follows some of the most logical treatment strategies in all of clinical neurology, the optimal means for removing copper from the brain (and elsewhere) have not achieved consensus.' Articles by <a href="#118" class="mim-tip-reference" title="Walshe, J. M. &lt;strong&gt;Penicillamine: the treatment of first choice for patients with Wilson&#x27;s disease.&lt;/strong&gt; Mov. Disord. 14: 545-550, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10435489/&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;10435489&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/1531-8257(199907)14:4&lt;545::aid-mds1001&gt;3.0.co;2-u&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="10435489">Walshe (1999)</a>, who defended the use of penicillamine, and by <a href="#16" class="mim-tip-reference" title="Brewer, G. J. &lt;strong&gt;Penicillamine should not be used as initial therapy in Wilson&#x27;s disease.&lt;/strong&gt; Mov. Disord. 14: 551-554, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10435490/&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;10435490&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/1531-8257(199907)14:4&lt;551::aid-mds1002&gt;3.0.co;2-s&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="10435490">Brewer (1999)</a> indicated that the role of penicillamine, now in its fifth decade of use, is still a matter of great controversy. <a href="#16" class="mim-tip-reference" title="Brewer, G. J. &lt;strong&gt;Penicillamine should not be used as initial therapy in Wilson&#x27;s disease.&lt;/strong&gt; Mov. Disord. 14: 551-554, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10435490/&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;10435490&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/1531-8257(199907)14:4&lt;551::aid-mds1002&gt;3.0.co;2-s&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="10435490">Brewer (1999)</a> suggested that penicillamine should not be used as initial therapy in Wilson disease. He cited a number of instances of penicillamine-induced worsening. He favored the use of zinc acetate for maintenance therapy of Wilson disease and mentioned other alternative therapies. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10435490+10435491+10435489" 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>By genetic analysis, <a href="#125" class="mim-tip-reference" title="Wu, Z.-Y., Lin, M.-T., Murong, S.-X., Wang, N. &lt;strong&gt;Molecular diagnosis and prophylactic therapy for presymptomatic Chinese patients with Wilson disease.&lt;/strong&gt; Arch. Neurol. 60: 737-741, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12756138/&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;12756138&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.60.5.737&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="12756138">Wu et al. (2003)</a> identified 17 presymptomatic patients with Wilson disease. Prophylactic treatment of 14 patients with zinc over 3 to 5 years resulted in decreased levels of urinary copper, which indicated effective control of copper metabolism. None of the patients developed clinical symptoms of Wilson disease or adverse effects of zinc therapy by the end of the study period. In contrast, 3 patients who refused treatment had symptomatic progression of the disease. <a href="#125" class="mim-tip-reference" title="Wu, Z.-Y., Lin, M.-T., Murong, S.-X., Wang, N. &lt;strong&gt;Molecular diagnosis and prophylactic therapy for presymptomatic Chinese patients with Wilson disease.&lt;/strong&gt; Arch. Neurol. 60: 737-741, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12756138/&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;12756138&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.60.5.737&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="12756138">Wu et al. (2003)</a> concluded that presymptomatic DNA diagnosis of individuals at risk and zinc therapy are effective treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12756138" 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>Treatment for patients with Wilson disease who present with neurologic manifestations is difficult because penicillamine often makes them neurologically worse and zinc is slow acting. <a href="#14" class="mim-tip-reference" title="Brewer, G. J., Hedera, P., Kluin, K. J., Carlson, M., Askari, F., Dick, R. B., Sitterly, J., Fink, J. K. &lt;strong&gt;Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy.&lt;/strong&gt; Arch. Neurol. 60: 379-385, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12633149/&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;12633149&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.60.3.379&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="12633149">Brewer et al. (2003)</a> performed an open-label study of 55 untreated patients presenting with neurologic Wilson disease and treated them with tetrathiomolybdate varying from 120 to 410 mg/day for 8 weeks and then followed up for 3 years. Only 2 patients treated with tetrathiomolybdate (4%) showed neurologic deterioration, compared with an estimated 50% of penicillamine-treated patients. Five of the 22 new patients exhibited bone marrow suppression and 3 had aminotransferase elevations. These numbers were higher than in the original 33 patients and appeared to be due primarily to a more rapid dose escalation. <a href="#14" class="mim-tip-reference" title="Brewer, G. J., Hedera, P., Kluin, K. J., Carlson, M., Askari, F., Dick, R. B., Sitterly, J., Fink, J. K. &lt;strong&gt;Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy.&lt;/strong&gt; Arch. Neurol. 60: 379-385, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12633149/&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;12633149&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.60.3.379&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="12633149">Brewer et al. (2003)</a> concluded that tetrathiomolybdate shows excellent efficacy in patients with Wilson disease who present with neurologic manifestations. With rapid escalation of dose, adverse effects from bone marrow suppression or aminotransferase elevations can occur. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12633149" 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 randomized controlled double-blind study of 48 patients with neurologic presentation of Wilson disease, <a href="#11" class="mim-tip-reference" title="Brewer, G. J., Askari, F., Lorincz, M. T., Carlson, M., Schilsky, M., Kluin, K. J., Hedera, P., Moretti, P., Fink, J. K., Tankanow, R., Dick, R. B., Sitterly, J. &lt;strong&gt;Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease.&lt;/strong&gt; Arch. Neurol. 63: 521-527, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16606763/&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;16606763&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.63.4.521&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="16606763">Brewer et al. (2006)</a> concluded that tetrathiomolybdate was a better choice than trientine for preserving neurologic function. Six (26%) of 23 patients treated with trientine showed neurologic deterioration during the 8-week study compared to 1 (4%) of 25 patients treated with tetrathiomolybdate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16606763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Alvarez, H. M., Xue, Y., Robinson, C. D., Canalizo-Hernandez, M. A., Marvin, R. G., Kelly, R. A., Mondragon, A., Penner-Hahn, J. E., O&#x27;Halloran, T. V. &lt;strong&gt;Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation.&lt;/strong&gt; Science 327: 331-334, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19965379/&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;19965379&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19965379[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/10.1126/science.1179907&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="19965379">Alvarez et al. (2010)</a> described how tetrathiomolybdate (TM) inhibits proteins that regulate copper physiology. Crystallographic results revealed that the surprising stability of the drug complex with the metallochaperone Atx1 (<a href="/entry/602270">602270</a>) arises from formation of a sulfur-bridged copper-molybdenum cluster reminiscent of those found in molybdenum and iron sulfur proteins. Spectroscopic studies indicated that this cluster is stable in solution and corresponds to physiologic clusters isolated from TM-treated Wilson disease animal models. Finally, mechanistic studies showed that the drug-metallochaperone inhibits metal transfer functions between copper-trafficking proteins. <a href="#1" class="mim-tip-reference" title="Alvarez, H. M., Xue, Y., Robinson, C. D., Canalizo-Hernandez, M. A., Marvin, R. G., Kelly, R. A., Mondragon, A., Penner-Hahn, J. E., O&#x27;Halloran, T. V. &lt;strong&gt;Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation.&lt;/strong&gt; Science 327: 331-334, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19965379/&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;19965379&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19965379[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/10.1126/science.1179907&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="19965379">Alvarez et al. (2010)</a> concluded that their results are consistent with a model wherein TM can directly and reversibly downregulate copper delivery to secreted metalloenzymes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19965379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a large inbred kindred with affected persons in 2 generations, <a href="#42" class="mim-tip-reference" title="Frydman, M., Bonne-Tamir, B., Farrer, L. A., Conneally, P. M., Magazanik, A., Ashbel, S., Goldwitch, Z. &lt;strong&gt;Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase D locus.&lt;/strong&gt; Proc. Nat. Acad. Sci. 82: 1819-1821, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3856863/&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;3856863&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.82.6.1819&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="3856863">Frydman et al. (1985)</a> investigated linkage of WND with 27 autosomal markers. A lod score of 3.21 was found at theta = 0.06 for linkage of WND and esterase D (ESD; <a href="/entry/133280">133280</a>) on chromosome 13. In a note added in proof, they indicated that they had typed a second unrelated 10-member sibship with WND; the maximum lod score was 1.48 at theta = 0, giving a combined maximum lod score of 4.55 at theta = 0.04. Bonne-Tamir et al. (<a href="#8" class="mim-tip-reference" title="Bonne-Tamir, B., Farrer, L. A., Frydman, M., Kanani, C. &lt;strong&gt;The locus for Wilson disease linked to esterase D in two Druze kindreds. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 37: A47, 1985."None>1985</a>, <a href="#7" class="mim-tip-reference" title="Bonne-Tamir, B., Farrer, L. A., Frydman, M., Kanaaneh, H. &lt;strong&gt;Evidence for linkage between Wilson disease and esterase D in three kindreds: detection of linkage for an autosomal recessive disorder by the family study method.&lt;/strong&gt; Genet. Epidemiol. 3: 201-209, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3459695/&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;3459695&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/gepi.1370030307&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="3459695">1986</a>) corroborated the linkage of WND and esterase D by studies of another inbred group, 2 unrelated Druze kindreds. The combined lod score was 5.49 at theta = 0.03. <a href="#7" class="mim-tip-reference" title="Bonne-Tamir, B., Farrer, L. A., Frydman, M., Kanaaneh, H. &lt;strong&gt;Evidence for linkage between Wilson disease and esterase D in three kindreds: detection of linkage for an autosomal recessive disorder by the family study method.&lt;/strong&gt; Genet. Epidemiol. 3: 201-209, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3459695/&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;3459695&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/gepi.1370030307&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="3459695">Bonne-Tamir et al. (1986)</a> confirmed the localization of Wilson disease by demonstration of linkage to DNA markers on chromosome 13; their studies indicated that the WND locus is distal to the ESD locus. <a href="#126" class="mim-tip-reference" title="Yuzbasiyan-Gurkan, V., Brewer, G. J., Boerwinkle, E., Venta, P. J. &lt;strong&gt;Linkage of the Wilson disease gene to chromosome 13 in North-American pedigrees.&lt;/strong&gt; Am. J. Hum. Genet. 42: 825-829, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3163469/&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;3163469&lt;/a&gt;]" pmid="3163469">Yuzbasiyan-Gurkan et al. (1988)</a> confirmed the linkage to markers on chromosome 13, with a maximum lod score of 2.189 at theta = 0.06 for linkage of Wilson disease to D13S1. One very informative pedigree was Hispanic. One pedigree in which affected persons had normal or low normal levels of serum ceruloplasmin (a finding in only about 15% of WND patients) showed a negative lod score. The proband was not on oral contraceptives, and there was no known ceruloplasmin-inducing factor present. The family was of Russian-Jewish background. By genetic linkage studies, <a href="#10" class="mim-tip-reference" title="Bowcock, A. M., Farrer, L. A., Hebert, J. M., Agger, M., Sternlieb, I., Scheinberg, I. H., Buys, C. H. C. M., Scheffer, H., Frydman, M., Chajek-Saul, T., Bonne-Tamir, B., Cavalli-Sforza, L. L. &lt;strong&gt;Eight closely linked loci place the Wilson disease locus within 13q14-q21.&lt;/strong&gt; Am. J. Hum. Genet. 43: 664-674, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3189332/&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;3189332&lt;/a&gt;]" pmid="3189332">Bowcock et al. (1988)</a> narrowed the assignment of the WND locus to 13q14-q21. <a href="#32" class="mim-tip-reference" title="Farrer, L. A., Bonne-Tamir, B., Frydman, M., Magazanik, A., Kidd, K. K., Bowcock, A. M., Cavalli-Sforza, L. L. &lt;strong&gt;Predicting genotypes at loci for autosomal recessive disorders using linked genetic markers: application to Wilson&#x27;s disease.&lt;/strong&gt; Hum. Genet. 79: 109-117, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3164701/&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;3164701&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00280547&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="3164701">Farrer et al. (1988)</a> explored the use of linked genetic markers to identify carriers, normals, and presymptomatic affected persons. A significant decrease on the average was found in serum copper concentrations in heterozygotes, but other sources of variation in serum copper concentration were much greater and precluded use of serum copper for carrier detection. A familial component, independent of WND genotype, appeared to be a major factor accounting for variation in ceruloplasmin levels among unaffected persons. <a href="#36" class="mim-tip-reference" title="Figus, A., Lampis, R., Devoto, M., Ristaldi, M. S., Ideo, A., De Virgiliis, S., Nurchi, A. M., Corrias, A., Corda, R., Lai, M. E., Tocco, A., Deplano, A., Solinas, A., Zancan, L., Lee, W.-H., Cao, A., Pirastu, M., Balestrieri, A. &lt;strong&gt;Carrier detection and early diagnosis of Wilson&#x27;s disease by restriction fragment length polymorphism analysis.&lt;/strong&gt; J. Med. Genet. 26: 78-82, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2563776/&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;2563776&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.26.2.78&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="2563776">Figus et al. (1989)</a> found no recombination with ESD and found linkage to several RFLPs. With ESD and 1 closely linked RFLP, they could either define the carrier status or exclude homozygosity in most unaffected sibs. The linkage of the WND locus to ESD at 13q14 was first shown by studies using the isozymic polymorphism of esterase D in families of Middle Eastern origin. Using RFLPs detected by the ESD cDNA, <a href="#60" class="mim-tip-reference" title="Houwen, R. H. J., Scheffer, H., te Meerman, G. J., van der Vlies, P., Buys, C. H. C. M. &lt;strong&gt;Close linkage of the Wilson&#x27;s disease locus to D13S12 in the chromosomal region 13q21 and not to ESD in 13q14.&lt;/strong&gt; Hum. Genet. 85: 560-562, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2227943/&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;2227943&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00194238&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="2227943">Houwen et al. (1990)</a> could not confirm this reported close linkage in an analysis of 17 families of northwestern European origin. However, no crossovers were detected in 63 meioses informative for linkage with marker D13S12, located more distally at 13q21. The data confirmed the assignment of WND to 13q14-q21. Its localization, however, seemed to be more distal to ESD than previously reported. In a study of 20 families, <a href="#95" class="mim-tip-reference" title="Scheffer, H., Houwen, R. H. J., Te Meerman, G. J., Loessner, J., Bachmann, B., Kunert, E., Verlind, E., Buys, C. H. C. M. &lt;strong&gt;Identification of crossovers in Wilson disease families as reference points for a genetic localization of the gene.&lt;/strong&gt; Hum. Genet. 89: 607-611, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1511977/&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;1511977&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00221947&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="1511977">Scheffer et al. (1992)</a> found that D13S31 was the closest proximal marker and D13S55 and D13S26 the closest distal markers. They identified a crossover between WND and D13S31 in 1 family and a crossover between WND and D13S55 in another. These crossover sites could be used as reference points for new chromosome 13q14-q21 markers for a more accurate mapping of the WND locus. Using D13S31 and D13S59 (the closest proximal and distal markers, respectively, for the WND locus) in fluorescence in situ hybridization studies of chromosomal aberrations, <a href="#65" class="mim-tip-reference" title="Kooy, R. F., Van der Veen, A. Y., Verlind, E., Houwen, R. H. J., Scheffer, H., Buys, C. H. C. M. &lt;strong&gt;Physical localisation of the chromosomal marker D13S31 places the Wilson disease locus at the junction of bands q14.3 and q21.1 of chromosome 13.&lt;/strong&gt; Hum. Genet. 91: 504-506, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8314565/&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;8314565&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00217780&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="8314565">Kooy et al. (1993)</a> determined that the Wilson disease locus is located at the junction of bands q14.3 and q21.1. In 51 families with Wilson disease, <a href="#107" class="mim-tip-reference" title="Thomas, G. R., Bull, P. C., Roberts, E. A., Walshe, J. M., Cox, D. W. &lt;strong&gt;Haplotype studies in Wilson disease.&lt;/strong&gt; Am. J. Hum. Genet. 54: 71-78, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8279472/&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;8279472&lt;/a&gt;]" pmid="8279472">Thomas et al. (1994)</a> studied DNA haplotypes of CA dinucleotide repeat polymorphisms in the 13q14.3 region. They found that 3 markers (D13S314, D13S133, and D13S316) showed nonrandom distribution on chromosomes carrying the WND mutation. They also found that haplotypes of these 3 markers had highly significant differences between WND and normal haplotypes in northern European families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3459695+3189332+2227943+8279472+3164701+3163469+8314565+1511977+3856863+2563776" 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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<strong>Inheritance</strong>
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<p>The transmission pattern of Wilson disease in the patients reported by <a href="#18" class="mim-tip-reference" title="Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. &lt;strong&gt;The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.&lt;/strong&gt; Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8298639/&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;8298639&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1293-327&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="8298639">Bull et al. (1993)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298639" 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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<strong>Molecular Genetics</strong>
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<p><a href="#18" class="mim-tip-reference" title="Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. &lt;strong&gt;The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.&lt;/strong&gt; Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8298639/&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;8298639&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1293-327&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="8298639">Bull et al. (1993)</a> identified 2 patients with Wilson disease who were homozygous for a 7-bp deletion within the coding region of the ATP7B gene (<a href="/entry/606882#0001">606882.0001</a>). <a href="#104" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. &lt;strong&gt;The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.&lt;/strong&gt; Nature Genet. 5: 344-350, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8298641/&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;8298641&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1293-344&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="8298641">Tanzi et al. (1993)</a> identified 4 mutations in the ATP7B gene in unrelated persons with Wilson disease: 2 missense mutations (<a href="/entry/606882#0002">606882.0002</a>-<a href="/entry/606882#0003">606882.0003</a>) and 2 frameshift mutations resulting in a truncated gene product (<a href="/entry/606882#0004">606882.0004</a>-<a href="/entry/606882#0005">606882.0005</a>). The mutations were found among 50 unrelated families derived predominantly from the United States, 18 unrelated families from Russia, and 5 presumably unrelated families from Sicily. Clearly, <a href="#18" class="mim-tip-reference" title="Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W. &lt;strong&gt;The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.&lt;/strong&gt; Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8298639/&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;8298639&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1293-327&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="8298639">Bull et al. (1993)</a> and <a href="#104" class="mim-tip-reference" title="Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C. &lt;strong&gt;The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.&lt;/strong&gt; Nature Genet. 5: 344-350, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8298641/&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;8298641&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1293-344&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="8298641">Tanzi et al. (1993)</a> had independently isolated the same gene which was convincingly the one mutant in Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8298639+8298641" 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="#108" class="mim-tip-reference" title="Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W. &lt;strong&gt;The Wilson disease gene: spectrum of mutations and their consequences.&lt;/strong&gt; Nature Genet. 9: 210-217, 1995. Note: Erratum:. Nature Genet. 9: 451 only, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7626145/&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;7626145&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0295-210&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="7626145">Thomas et al. (1995)</a> reviewed the mutations found in the ATP7B gene. Their findings suggest a wide span in the age of onset of Wilson disease, perhaps wider than previously considered typical. Mutations that completely disrupt the gene can produce liver disease in early childhood at a time when Wilson disease may not be considered in the differential diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7626145" 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="#89" class="mim-tip-reference" title="Petrukhin, K., Fischer, S. G., Pirastu, M., Tanzi, R. E., Chernov, I., Devoto, M., Brzustowicz, L. M., Cayanis, E., Vitale, E., Russo, J. J., Matseoane, D., Boukhgalter, B., Wasco, W., Figus, A. L., Loudianos, J., Cao, A., Sternlieb, I., Evgrafov, O., Parano, E., Pavone, L., Warburton, D., Ott, J., Penchaszadeh, G. K., Scheinberg, I. H., Gilliam, T. C. &lt;strong&gt;Mapping, cloning and genetic characterization of the region containing the Wilson disease gene.&lt;/strong&gt; Nature Genet. 5: 338-343, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8298640/&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;8298640&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1293-338&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="8298640">Petrukhin et al. (1993)</a> identified YACs spanning the Wilson disease region and derived cosmid contigs therefrom. Thirteen microsatellite markers were generated from cosmids and used for study of genetic equilibrium (linkage disequilibrium; LD). Strong LD was detected between these markers and the WND locus in 28 families from rural Russia, 43 families from Sardinia, and 67 families of predominantly North American and European descent. From their haplotype and mutation analyses, <a href="#89" class="mim-tip-reference" title="Petrukhin, K., Fischer, S. G., Pirastu, M., Tanzi, R. E., Chernov, I., Devoto, M., Brzustowicz, L. M., Cayanis, E., Vitale, E., Russo, J. J., Matseoane, D., Boukhgalter, B., Wasco, W., Figus, A. L., Loudianos, J., Cao, A., Sternlieb, I., Evgrafov, O., Parano, E., Pavone, L., Warburton, D., Ott, J., Penchaszadeh, G. K., Scheinberg, I. H., Gilliam, T. C. &lt;strong&gt;Mapping, cloning and genetic characterization of the region containing the Wilson disease gene.&lt;/strong&gt; Nature Genet. 5: 338-343, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8298640/&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;8298640&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1293-338&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="8298640">Petrukhin et al. (1993)</a> predicted that approximately half of all Wilson disease mutations will be rare in the American and Russian populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298640" 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>Given the difficulties of searching for mutations in a gene spanning more than 80 kb of genomic DNA, haplotype data are important as a guide to mutation detection. <a href="#110" class="mim-tip-reference" title="Thomas, G. R., Roberts, E. A., Walshe, J. M., Cox, D. W. &lt;strong&gt;Haplotypes and mutations in Wilson disease.&lt;/strong&gt; Am. J. Hum. Genet. 56: 1315-1319, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7762553/&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;7762553&lt;/a&gt;]" pmid="7762553">Thomas et al. (1995)</a> did haplotyping of the Wilson disease gene region in 58 families. These haplotypes, combining 3 markers (D13S314, D13S316, and D13S301), were usually specific for each different mutation. The haplotype data suggested that as many as 20 mutations might still be unidentified; a total of 25 disease-causing mutations had been identified at that time. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762553" 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="genotypePhenotypeCorrelations" class="mim-anchor"></a>
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<p><a href="#48" class="mim-tip-reference" title="Gromadzka, G., Schmidt, H. H.-J., Genschel, J., Bochow, B., Rodo, M., Tarnacka, B., Litwin, T., Chabik, G., Czlonkowska, A. &lt;strong&gt;Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson&#x27;s disease.&lt;/strong&gt; Clin. Genet. 68: 524-532, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16283883/&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;16283883&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2005.00528.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="16283883">Gromadzka et al. (2005)</a> studied 142 Polish patients with Wilson disease and identified 26 mutations in the ATP7B gene: 11 truncating, 14 missense, and 1 splice site mutation. Patients with 1 or 2 truncating mutations on their alleles had lower serum copper and ceruloplasmin levels and were younger when the first symptoms of the disease appeared compared with individuals with 2 missense mutations, and the effect of truncating mutations on phenotype was dose-dependent. <a href="#48" class="mim-tip-reference" title="Gromadzka, G., Schmidt, H. H.-J., Genschel, J., Bochow, B., Rodo, M., Tarnacka, B., Litwin, T., Chabik, G., Czlonkowska, A. &lt;strong&gt;Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson&#x27;s disease.&lt;/strong&gt; Clin. Genet. 68: 524-532, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16283883/&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;16283883&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2005.00528.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="16283883">Gromadzka et al. (2005)</a> found no association between type of ATP7B mutation and mode of initial disease presentation (neurologic, hepatic, or mixed). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16283883" 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="populationGenetics" class="mim-anchor"></a>
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<strong>Population Genetics</strong>
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<p><a href="#35" class="mim-tip-reference" title="Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others. &lt;strong&gt;Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.&lt;/strong&gt; Am. J. Hum. Genet. 57: 1318-1324, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8533760/&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;8533760&lt;/a&gt;]" pmid="8533760">Figus et al. (1995)</a> stated that the worldwide prevalence of Wilson disease is estimated to be on the order of 30 per 1 million, with a gene frequency of 0.56% and a carrier frequency of 1 in 90. They noted that a higher prevalence seems to exist in Sardinia, where approximately 10-12 new cases per year are identified. <a href="#35" class="mim-tip-reference" title="Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others. &lt;strong&gt;Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.&lt;/strong&gt; Am. J. Hum. Genet. 57: 1318-1324, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8533760/&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;8533760&lt;/a&gt;]" pmid="8533760">Figus et al. (1995)</a> analyzed mutations and defined the chromosomal haplotype in 127 patients of Mediterranean descent affected by Wilson disease: 39 Sardinians, 49 Italians, 33 Turks, and 6 Albanians. There were 5 common haplotypes in Sardinians, 3 in Italians, and 2 in Turks, which accounted for 85%, 32%, and 30% of the Wilson disease chromosomes, respectively. They identified 16 novel mutations: 8 frameshifts, 7 missense mutations, and 1 splicing defect. In addition, they detected 5 previously described mutations, e.g., his1070-to-gln (<a href="/entry/606882#0006">606882.0006</a>), which accounted for 13% of the mutations in WND chromosomes in non-Sardinian Mediterranean populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533760" 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 the Sardinian population, one haplotype accounts for 55% of WND chromosomes (<a href="#35" class="mim-tip-reference" title="Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others. &lt;strong&gt;Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.&lt;/strong&gt; Am. J. Hum. Genet. 57: 1318-1324, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8533760/&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;8533760&lt;/a&gt;]" pmid="8533760">Figus et al., 1995</a>). <a href="#76" class="mim-tip-reference" title="Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Figus, A., Lilliu, F., De Virgiliis, S., Nurchi, A. M., Deplano, A., Moi, P., Pirastu, M., Cao, A. &lt;strong&gt;Molecular characterization of Wilson disease in the Sardinian population--evidence of a founder effect.&lt;/strong&gt; Hum. Mutat. 14: 294-303, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10502776/&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;10502776&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(199910)14:4&lt;294::AID-HUMU4&gt;3.0.CO;2-9&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="10502776">Loudianos et al. (1999)</a> characterized the putative promoter and 5-prime untranslated region of the WND gene and carried out mutation analysis in this region in Sardinian patients with WND with the most common haplotype. They detected a single mutation resulting from a 15-nucleotide deletion (<a href="/entry/606882#0010">606882.0010</a>) in all chromosomes with this common haplotype. With the addition of this mutation, the molecular defect has been found in 92% of the WD chromosomes in Sardinians. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8533760+10502776" 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="#77" class="mim-tip-reference" title="Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Nurchi, A., Sturniolo, G. C., Marcellini, M., Zancan, L., Bragetti, P., Akar, N., Yagci, R., Vegnente, A., Cao, A., Pirastu, M. &lt;strong&gt;Further delineation of the molecular pathology of Wilson disease in the Mediterranean population.&lt;/strong&gt; Hum. Mutat. 12: 89-94, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9671269/&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;9671269&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1998)12:2&lt;89::AID-HUMU3&gt;3.0.CO;2-G&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="9671269">Loudianos et al. (1998)</a> performed a mutation screen on the WND gene in 59 patients of Mediterranean origin: 26 Continental Italians, 22 Sardinians, 9 Turkish, and 2 Albanians. They found 31 novel and 3 known mutations. Most of the patients were compound heterozygotes. Because there are so many causative mutations, the preclinical and prenatal diagnosis of Wilson disease should be carried out by a combination of mutation and linkage analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9671269" 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="#52" class="mim-tip-reference" title="Ha-Hao, D., Hefter, H., Stremmel, W., Castaneda-Guillot, C., Hernandez, A. H., Cox, D. W., Auburger, G. &lt;strong&gt;His1069-to-gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.&lt;/strong&gt; Europ. J. Hum. Genet. 6: 616-623, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9887381/&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;9887381&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/sj.ejhg.5200237&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="9887381">Ha-Hao et al. (1998)</a> performed mutation analysis in 33 German and 10 Cuban unrelated Wilson disease patients. The common his1069-to-gln (<a href="/entry/606882#0006">606882.0006</a>) mutation accounted for 42% of all WND chromosomes in the German series and haplotype C was found to be highly predictive for this mutation. Six previously undescribed WND gene mutations were identified. In 15 German WND index patients and 3 sibs, both WND mutations could be determined and a genotype-phenotype correlation was attempted. Patients homozygous for the his1069-to-gln mutation showed almost a complete range of clinical presentations; thus, in this study, the his1069-to-gln mutation was not associated with a late neurologic presentation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887381" 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="#64" class="mim-tip-reference" title="Kim, E. K., Yoo, O. J., Song, K. Y., Yoo, H. W., Choi, S. Y., Cho, S. W., Hahn, S. H. &lt;strong&gt;Identification of three novel mutations and a high frequency of the arg778-to-leu mutation in Korean patients with Wilson disease.&lt;/strong&gt; Hum. Mutat. 11: 275-278, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9554743/&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;9554743&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1998)11:4&lt;275::AID-HUMU4&gt;3.0.CO;2-L&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="9554743">Kim et al. (1998)</a> identified 3 novel mutations in the ATP7B gene in Korean patients with Wilson disease. One of these, arg778 to leu (R778L; <a href="/entry/606882#0009">606882.0009</a>), was found in 6 of 8 unrelated patients, giving an allele frequency of 37.5%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554743" 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 120 unrelated Korean patients with Wilson disease, <a href="#87" class="mim-tip-reference" title="Park, S., Park, J.-Y., Kim, G.-H., Choi, J.-H., Kim, K.-M., Kim, J.-B., Yoo, H.-W. &lt;strong&gt;Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease.&lt;/strong&gt; Hum. Mutat. 28: 1108-1113, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17587212/&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;17587212&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.20574&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="17587212">Park et al. (2007)</a> identified 28 different mutations, including 6 novel mutations, in the ATP7B gene. They identified R778L as the most common mutation, occurring in 39.2% of mutant alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17587212" 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 the Korean population, <a href="#86" class="mim-tip-reference" title="Park, H.-D., Ki, C.-S., Lee, S.-Y., Kim, J.-W. &lt;strong&gt;Carrier frequency of the R778L, A874V, and N1270S mutations in the ATP7B gene in a Korean population. (Letter)&lt;/strong&gt; Clin. Genet. 75: 405-407, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19419418/&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;19419418&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2008.01132.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="19419418">Park et al. (2009)</a> found that the combined carrier frequency of 3 common ATP7B mutations, R778L, A874V (<a href="/entry/606882#0016">606882.0016</a>), and N1270S (<a href="/entry/606882#0017">606882.0017</a>), was 1 in 50 (2%). Extrapolating from this figure, the authors estimated that the carrier frequency of Wilson disease is about 1 in 27 in the Korean population, suggesting that the disorder is more common than in U.S. Caucasian populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19419418" 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="#83" class="mim-tip-reference" title="Okada, T., Shiono, Y., Hayashi, H., Satoh, H., Sawada, T., Suzuki, A., Takeda, Y., Yano, M., Michitaka, K., Onji, M., Mabuchi, H. &lt;strong&gt;Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson&#x27;s disease.&lt;/strong&gt; Hum. Mutat. 15: 454-462, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10790207/&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;10790207&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(200005)15:5&lt;454::AID-HUMU7&gt;3.0.CO;2-J&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="10790207">Okada et al. (2000)</a> analyzed the ATP7B gene in 41 unrelated Japanese Wilson disease families, including 47 patients. They identified 21 mutations, 9 of which were novel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790207" 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="#44" class="mim-tip-reference" title="Garcia-Villarreal, L., Daniels, S., Shaw, S. H., Cotton, D., Galvin, M., Geskes, J., Bauer, P., Sierra-Hernandez, A., Buckler, A., Tugores, A. &lt;strong&gt;High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.&lt;/strong&gt; Hepatology 32: 1329-1336, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11093740/&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;11093740&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1053/jhep.2000.20152&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="11093740">Garcia-Villarreal et al. (2000)</a> identified a founder mutation in the ATP7B gene (L708P; <a href="/entry/606882#0023">606882.0023</a>) in 18 individuals with Wilson disease from the Canary Islands of Spain. Twelve patients were homozygous for the mutation. Homozygous patients tended to have a neurologic presentation at an average age of 16 years. The L708P mutation was estimated to have arisen in Gran Canaria over 56 generations ago, in pre-Hispanic times. <a href="#44" class="mim-tip-reference" title="Garcia-Villarreal, L., Daniels, S., Shaw, S. H., Cotton, D., Galvin, M., Geskes, J., Bauer, P., Sierra-Hernandez, A., Buckler, A., Tugores, A. &lt;strong&gt;High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.&lt;/strong&gt; Hepatology 32: 1329-1336, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11093740/&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;11093740&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1053/jhep.2000.20152&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="11093740">Garcia-Villarreal et al. (2000)</a> estimated a prevalence for Wilson disease of 1 in 2,600 individuals in the Canary Islands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11093740" 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="#79" class="mim-tip-reference" title="Margarit, E., Bach, V., Gomez, D., Bruguera, M., Jara, P., Queralt, R., Ballesta, F. &lt;strong&gt;Mutation analysis of Wilson disease in the Spanish population--identification of a prevalent substitution and eight novel mutations in the ATP7B gene.&lt;/strong&gt; Clin. Genet. 68: 61-68, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15952988/&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;15952988&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2005.00439.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="15952988">Margarit et al. (2005)</a> analyzed 40 unrelated Spanish patients with Wilson disease and identified 21 different mutations in the ATP7B gene in 35 (87%) patients. The M645R (<a href="/entry/606882#0020">606882.0020</a>) mutation was particularly prevalent and found in 22 patients (55%), who were all compound heterozygotes for mutation in the ATP7B gene. In 6 patients in whom M645R was combined with a nonsense mutation, there was early onset of the disease, occurring between 5 and 14 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15952988" 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="#84" class="mim-tip-reference" title="Olivarez, L., Caggana, M., Pass, K. A., Ferguson, P., Brewer, G. J. &lt;strong&gt;Estimate of the frequency of Wilson&#x27;s disease in the US Caucasian population: a mutation analysis approach.&lt;/strong&gt; Ann. Hum. Genet. 65: 459-463, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11806854/&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;11806854&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1017/S0003480001008764&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="11806854">Olivarez et al. (2001)</a> undertook to estimate the frequency of Wilson disease in the U.S. Caucasian population. They used data from 4 studies to determine that approximately one-third of Wilson disease mutations in U.S. Caucasian Wilson disease patients are his1069-to-gln (H1069Q; <a href="/entry/606882#0006">606882.0006</a>). They then determined the frequency of this mutation in random DNA samples from 2,601 U.S. Caucasian newborns to be 0.285%. Multiplying by 3 gave an estimated Wilson disease heterozygote frequency of 0.855% and an allele frequency of 0.428%, or 0.00428. These data gave a Wilson disease frequency of about 1 in 55,000 births. The 95% confidence interval was rather broad, ranging from about 1 in 18,000 to 1 in 700,000 births. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11806854" 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="#51" class="mim-tip-reference" title="Gupta, A., Aikath, D., Neogi, R., Datta, S., Basu, K., Maity, B., Trivedi, R., Ray, J., Das, S. K., Gangopadhyay, P. K., Ray, K. &lt;strong&gt;Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype-phenotype correlation in Indian patients.&lt;/strong&gt; Hum. Genet. 118: 49-57, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16133174/&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;16133174&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-005-0007-y&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="16133174">Gupta et al. (2005)</a> analyzed Indian patients with Wilson disease from 62 unrelated families and their first-degree relatives and identified a total of 9 mutations, 5 novel, in the ATP7B gene. The authors noted that homozygotes for different mutations that would be expected to produce similar defective proteins showed significant disparity in terms of organ involvement and severity of disease; in 1 family, 2 sibs with the same pair of mutant chromosomes had remarkably different phenotypes. <a href="#51" class="mim-tip-reference" title="Gupta, A., Aikath, D., Neogi, R., Datta, S., Basu, K., Maity, B., Trivedi, R., Ray, J., Das, S. K., Gangopadhyay, P. K., Ray, K. &lt;strong&gt;Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype-phenotype correlation in Indian patients.&lt;/strong&gt; Hum. Genet. 118: 49-57, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16133174/&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;16133174&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-005-0007-y&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="16133174">Gupta et al. (2005)</a> suggested that there may be as yet unidentified modifying loci that account for the observed phenotypic heterogeneity among patients with Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16133174" 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="#78" class="mim-tip-reference" title="Mak, C. M., Lam, C.-W., Tam, S., Lai, C.-L., Chan, L.-Y., Fan, S.-T., Lau, Y.-L., Lai, S.-T., Yuen, P., Hui, J., Fu, C.-C., Wong, K.-S., and 13 others. &lt;strong&gt;Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: identification of 17 novel mutations and its genetic heterogeneity.&lt;/strong&gt; J. Hum. Genet. 53: 55-63, 2008. Note: Erratum: J. Hum. Genet. 53: 375 only, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18034201/&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;18034201&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10038-007-0218-2&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="18034201">Mak et al. (2008)</a> sequenced the ATP7B gene in 65 unrelated Han Chinese patients with Wilson disease and identified 126 disease alleles in 129 chromosomes (97.6% detection rate); the most prevalent mutation, R778L (<a href="/entry/606882#0009">606882.0009</a>), was found in 22 chromosomes. The authors screened 660 healthy Hong Kong Han Chinese for R778L and a 2310C-G SNP in perfect linkage disequilibrium with R778L, and identified 3 carriers of both; neither variant was found in the remaining 657 individuals. <a href="#78" class="mim-tip-reference" title="Mak, C. M., Lam, C.-W., Tam, S., Lai, C.-L., Chan, L.-Y., Fan, S.-T., Lau, Y.-L., Lai, S.-T., Yuen, P., Hui, J., Fu, C.-C., Wong, K.-S., and 13 others. &lt;strong&gt;Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: identification of 17 novel mutations and its genetic heterogeneity.&lt;/strong&gt; J. Hum. Genet. 53: 55-63, 2008. Note: Erratum: J. Hum. Genet. 53: 375 only, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18034201/&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;18034201&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10038-007-0218-2&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="18034201">Mak et al. (2008)</a> calculated the prevalence of Wilson disease to be 1 in 5,400 in Hong Kong Han Chinese, and the East Asian-specific R778L mutation was estimated to have arisen 5,500 years earlier from a single ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18034201" 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="#119" class="mim-tip-reference" title="Wang, L.-H., Huang, Y.-Q., Shang, X., Su, Q.-X., Xiong, F., Yu, Q.-Y., Lin, H.-P., Wei, Z.-S., Hong, M.-F., Xu, X.-M. &lt;strong&gt;Mutation analysis of 73 southern Chinese Wilson&#x27;s disease patients: identification of 10 novel mutations and its clinical correlation.&lt;/strong&gt; J. Hum. Genet. 56: 660-665, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21796144/&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;21796144&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/jhg.2011.76&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="21796144">Wang et al. (2011)</a> identified 38 different pathogenic ATP7B mutations in 69 (69.86%) of 73 Chinese patients with Wilson disease. The most common mutation was R778L, which accounted for 23.29% mutant alleles, and the second most common mutation was I1148T (<a href="/entry/606882#0025">606882.0025</a>), which accounted for 9.59% of mutant alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21796144" 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="#113" class="mim-tip-reference" title="Wallace, D. F., Dooley, J. S. &lt;strong&gt;ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.&lt;/strong&gt; Hum. Genet. 139: 1065-1075, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/32248359/&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;32248359&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-020-02161-3&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="32248359">Wallace and Dooley (2020)</a> found that of the 732 Wilson disease-associated ATP7B mutations cataloged in the Wilson Disease Mutation Database (2010) and reported in the literature (2010-2017), 231 were present in the gnomAD database, resulting in an ATP7B pathogenic allele frequency of 2.055% and a heterozygous carrier rate of 1 in 25. The subpopulation in gnomAD with highest pathogenic allele frequency was the Ashkenazi Jewish population (3.005%), and the subpopulation with lowest pathogenic allele frequency was the African population (1.245%). <a href="#113" class="mim-tip-reference" title="Wallace, D. F., Dooley, J. S. &lt;strong&gt;ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.&lt;/strong&gt; Hum. Genet. 139: 1065-1075, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/32248359/&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;32248359&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-020-02161-3&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="32248359">Wallace and Dooley (2020)</a> assessed the penetrance/pathogenicity of ATP7B mutations by comparing gnomAD allele frequencies with the number of reports of each mutation and then using a variant effect prediction algorithm. After excluding variants with predicted low penetrance, <a href="#113" class="mim-tip-reference" title="Wallace, D. F., Dooley, J. S. &lt;strong&gt;ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.&lt;/strong&gt; Hum. Genet. 139: 1065-1075, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/32248359/&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;32248359&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-020-02161-3&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="32248359">Wallace and Dooley (2020)</a> calculated Wilson disease prevalence to be 1 in 20,000 individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32248359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#73" class="mim-tip-reference" title="Li, Y., Togashi, Y., Sato, S., Emoto, T., Kang, J.-H., Takeichi, N., Kobayashi, H., Kojima, Y., Une, Y., Uchino, J. &lt;strong&gt;Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis: a model of Wilson&#x27;s disease.&lt;/strong&gt; J. Clin. Invest. 87: 1858-1861, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2022751/&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;2022751&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI115208&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="2022751">Li et al. (1991)</a> found biochemical and morphologic evidence to suggest that the Long-Evans Cinnamon (LEC) rat is an authentic model of Wilson disease. Canine copper toxicosis, an autosomal recessive disorder, is thought to be an authentic model of Wilson disease. <a href="#127" class="mim-tip-reference" title="Yuzbasiyan-Gurkan, V., Wagnitz, S., Blanton, S. H., Brewer, G. J. &lt;strong&gt;Linkage studies of the esterase D and retinoblastoma genes to canine copper toxicosis: a model for Wilson disease.&lt;/strong&gt; Genomics 15: 86-90, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8432554/&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;8432554&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1993.1013&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="8432554">Yuzbasiyan-Gurkan et al. (1993)</a> found, however, that in the dog the disorder is not linked (within 13% recombination) to the RB1 locus (<a href="/entry/614041">614041</a>) or (within 5% recombination) to the ESD locus (<a href="/entry/133280">133280</a>). Furthermore, ESD and RB1, tightly linked in both the mouse and human genomes, were not found to be closely linked in the canine genome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2022751+8432554" 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 the LEC rat, acute hepatitis develops spontaneously about 4 months after birth, with clinical features similar to those seen in human fulminant hepatitis, sometimes a feature of Wilson disease. Survivors of this often-fatal attack continue to suffer from chronic hepatitis and usually develop hepatocellular carcinoma at age 12 months or older. Copper is abnormally high in the liver of LEC rats, and hepatitis can be prevented by treatment with copper-chelating agents such as D-penicillamine. <a href="#124" class="mim-tip-reference" title="Wu, J., Forbes, J. R., Chen, H. S., Cox, D. W. &lt;strong&gt;The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene.&lt;/strong&gt; Nature Genet. 7: 541-545, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7951327/&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;7951327&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0894-541&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="7951327">Wu et al. (1994)</a> cloned cDNAs for the rat gene (Atp7b; <a href="/entry/606882">606882</a>) homologous to the human Wilson disease gene and used them to identify a partial deletion in the gene in the LEC rat. The deletion removed at least 900 basepairs of the coding region at the 3-prime end, including the crucial ATP-binding domain, and extended downstream of the gene. The usefulness of the model for studying liver pathophysiology, for developing therapy for Wilson disease, and for studying the pathway of copper transport and its possible interaction with other heavy metals was noted. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951327" 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="#106" class="mim-tip-reference" title="Theophilos, M. B., Cox, D. W., Mercer, J. F. B. &lt;strong&gt;The toxic milk mouse is a murine model of Wilson disease.&lt;/strong&gt; Hum. Molec. Genet. 5: 1619-1624, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8894697/&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;8894697&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/5.10.1619&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="8894697">Theophilos et al. (1996)</a> cloned and sequenced the murine homolog of the ATP7B gene. They demonstrated a point mutation in the 'toxic milk' (tx) mouse Atp7b gene. The coding sequence from the tx Atp7b gene was identical to the sequence from the DL mouse except for a single base change (A4066G) in the mutant sequence. <a href="#106" class="mim-tip-reference" title="Theophilos, M. B., Cox, D. W., Mercer, J. F. B. &lt;strong&gt;The toxic milk mouse is a murine model of Wilson disease.&lt;/strong&gt; Hum. Molec. Genet. 5: 1619-1624, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8894697/&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;8894697&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/5.10.1619&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="8894697">Theophilos et al. (1996)</a> reported that this base change led to a met1356-to-val amino acid substitution within the proposed eighth transmembrane domain of the Atp7b protein. <a href="#106" class="mim-tip-reference" title="Theophilos, M. B., Cox, D. W., Mercer, J. F. B. &lt;strong&gt;The toxic milk mouse is a murine model of Wilson disease.&lt;/strong&gt; Hum. Molec. Genet. 5: 1619-1624, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8894697/&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;8894697&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/5.10.1619&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="8894697">Theophilos et al. (1996)</a> reviewed the pathophysiology of the disorder in the tx mouse. They noted that tx is an autosomal recessive mutation which leads to hepatic accumulation of copper from the third postnatal week. The pups are born with an apparent copper deficiency and the milk of the mutant mothers is deficient in copper, leading to continued copper deficiency in the pups. The authors noted that the pathology observed in the livers of the deficient mice shows significant differences from the liver pathology observed in Wilson disease. <a href="#61" class="mim-tip-reference" title="Huang, L., Gitschier, J. &lt;strong&gt;A novel gene involved in zinc transport is deficient in the lethal milk mouse.&lt;/strong&gt; Nature Genet. 17: 292-297, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9354792/&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;9354792&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1197-292&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="9354792">Huang and Gitschier (1997)</a> pointed out that tx, in which the milk of mutant dams is fatally deficient in copper, has a parallel in 'lethal milk' (lm) in which the milk of mutant dams is fatally deficient in zinc. Copper deficiency in human milk in Wilson disease has, it seems, not been investigated. The gene that is mutant in 'lethal milk' of the mouse is zinc transporter-4 (<a href="/entry/602095">602095</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9354792+8894697" 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>The mouse homologs for the Menkes (<a href="/entry/309400">309400</a>) and Wilson disease genes are the mottled (Atp7a; <a href="/entry/300011">300011</a>) and toxic milk (Atp7b) genes, respectively. These genes encode similar copper-transporting P-type ATPases. They are expressed in different adult tissues in patterns reflecting disease manifestations. Using RNA in situ hybridization, <a href="#67" class="mim-tip-reference" title="Kuo, Y.-M., Gitschier, J., Packman, S. &lt;strong&gt;Developmental expression of the mouse mottled and toxic milk genes suggests distinct functions for the Menkes and Wilson disease copper transporters.&lt;/strong&gt; Hum. Molec. Genet. 6: 1043-1049, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9215673/&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;9215673&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.7.1043&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="9215673">Kuo et al. (1997)</a> determined the distribution of mottled and toxic milk transcripts during mouse embryonic development. The mottled gene was expressed in all tissues throughout embryogenesis and was particularly strong in the choroid plexuses of the brain. Contrary to the previous observation of absent or very low expression in adult liver, mottled was expressed in embryonic liver. Expression of the toxic milk gene was significantly more delimited, with early expression in the central nervous system, heart, and liver. Later in gestation, toxic milk transcript was clearly seen in liver, intestine, thymus, and respiratory epithelium, including nasopharynx, trachea, and bronchi. In lung, toxic milk expression was restricted to bronchi, while mottled expression was diffuse. Hepatic expression of both toxic milk and mottled was in the parenchyma, as opposed to blood cells. These results suggested that the mottled gene product functions primarily in the homeostatic maintenance of cell copper levels, while the toxic milk gene product may be specifically involved in the biosynthesis of distinct cuproproteins in different tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215673" 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>Using homologous recombination to disrupt the normal translation of the Atp7b gene, <a href="#17" class="mim-tip-reference" title="Buiakova, O. I., Xu, J., Lutsenko, S., Zeitlin, S., Das, K., Das, S., Ross, B. M., Mekios, C., Scheinberg, I. H., Gilliam, T. C. &lt;strong&gt;Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation.&lt;/strong&gt; Hum. Molec. Genet. 8: 1665-1671, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10441329/&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;10441329&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/8.9.1665&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="10441329">Buiakova et al. (1999)</a> generated a strain of mice that were homozygous null mutants for the Wilson disease gene. The Atp7b-null mice displayed a gradual accumulation of hepatic copper that increased to a level 60-fold greater than normal by 5 months of age. An increase in copper concentration was also observed in the kidney, brain, placenta, and lactating mammary glands of homozygous mutants, although milk from the mutant glands was copper deficient. Morphologic abnormalities resembling cirrhosis developed in most animals older than 7 months of age. Progeny of the homozygous mutant females developed neurologic abnormalities and growth retardation characteristic of copper deficiency. Copper concentrations in the livers of the newborn homozygous null mutants were decreased dramatically. Thus, the authors concluded that inactivation of the murine Atp7b gene produces a form of cirrhotic liver disease that resembles Wilson disease in humans and the 'toxic milk' phenotype in mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441329" 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="#105" class="mim-tip-reference" title="Terada, K., Nakako, T., Yang, X.-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., Sugiyama, T. &lt;strong&gt;Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.&lt;/strong&gt; J. Biol. Chem. 273: 1815-1820, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9430732/&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;9430732&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1074/jbc.273.3.1815&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="9430732">Terada et al. (1998)</a> introduced human ATP7B cDNA into the LEC rat using recombinant adenovirus-mediated gene delivery. An immunofluorescence study and a subcellular fractionation study revealed the transgene expression in liver and its localization to the Golgi apparatus. Moreover, since the synthesis of holoceruloplasmin is disturbed in the LEC rat, the plasma level of holoceruloplasmin, oxidase-active and copper-bound form, was examined to evaluate the function of ATP7B protein with respect to copper transport. Holoceruloplasmin was found in plasma of LEC rats who received ATP7B cDNA. <a href="#105" class="mim-tip-reference" title="Terada, K., Nakako, T., Yang, X.-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., Sugiyama, T. &lt;strong&gt;Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.&lt;/strong&gt; J. Biol. Chem. 273: 1815-1820, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9430732/&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;9430732&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1074/jbc.273.3.1815&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="9430732">Terada et al. (1998)</a> concluded that introduced ATP7B protein may function in the copper transport coupled with the synthesis of ceruloplasmin and that the Golgi apparatus is the likely site for ATP7B protein to manifest its function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9430732" 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>By investigating the common autosomal recessive copper toxicosis in Bedlington terriers, <a href="#111" class="mim-tip-reference" title="van de Sluis, B. J. A., Breen, M., Nanji, M., van Wolferen, M., de Jong, P., Binns, M. M., Pearson, P. L., Kuipers, J., Rothuizen, J., Cox, D. W., Wijmenga, C., van Oost, B. A. &lt;strong&gt;Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13-p16.&lt;/strong&gt; Hum. Molec. Genet. 8: 501-507, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9949209/&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;9949209&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/8.3.501&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="9949209">van de Sluis et al. (1999)</a> identified a new locus involved in progressive liver disease. Whereas the ATP7B gene mapped to canine chromosome 22q11, CO4107, a microsatellite marker showing close linkage to copper toxicosis, mapped to canine chromosome 10q26. A transcribed sequence identified from a CO4107-containing BAC was found to be homologous to a gene expressed from human chromosome 2p16-p13, a region devoid of any positional candidate genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9949209" 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 mouse hepatocytes, <a href="#70" class="mim-tip-reference" title="Lang, P. A., Schenck, M., Nicolay, J. P., Becker, J. U., Kempe, D. S., Lupescu, A., Koka, S., Eisele, K., Klarl, B. A., Rubben, H., Schmid, K. W., Mann, K., Hildenbrand, S., Hefter, H., Huber, S. M., Wieder, T., Erhardt, A., Haussinger, D., Gulbins, E., Lang, F. &lt;strong&gt;Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide.&lt;/strong&gt; Nature Med. 13: 164-170, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17259995/&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;17259995&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nm1539&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="17259995">Lang et al. (2007)</a> demonstrated that Cu(2+) induced the secretion of activated acid sphingomyelinase (SMPD1; <a href="/entry/607608">607608</a>) from leukocytes, leading to ceramide release in and phosphatidylserine exposure on erythrocytes, which are events prevented by inhibition of Smpd1. In LEC rats, deficiency in or pharmacologic inhibition of Smpd1 prevented Cu(2+)-induced hepatocyte apoptosis and protected the rats from acute hepatocyte death, liver failure, and early death. Patients with Wilson disease showed elevated plasma levels of SMPD1 and displayed a constitutive increase of ceramide- and phosphatidylserine-positive erythrocytes. <a href="#70" class="mim-tip-reference" title="Lang, P. A., Schenck, M., Nicolay, J. P., Becker, J. U., Kempe, D. S., Lupescu, A., Koka, S., Eisele, K., Klarl, B. A., Rubben, H., Schmid, K. W., Mann, K., Hildenbrand, S., Hefter, H., Huber, S. M., Wieder, T., Erhardt, A., Haussinger, D., Gulbins, E., Lang, F. &lt;strong&gt;Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide.&lt;/strong&gt; Nature Med. 13: 164-170, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17259995/&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;17259995&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nm1539&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="17259995">Lang et al. (2007)</a> concluded that Cu(2+) triggers hepatocyte apoptosis through activation of acid sphingomyelinase and release of ceramide, suggesting a previously unidentified mechanism for liver cirrhosis and anemia in Wilson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17259995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>A tribute to Dr. S. A. Kinnier Wilson and a comprehensive review of Wilson disease were published in 1988; see <a href="#80" class="mim-tip-reference" title="Marsden, C. D., Fahn, S. &lt;strong&gt;Dr. S. A. Kinnier Wilson (1878-1937). (Editorial)&lt;/strong&gt; Mov. Disord. 3: 1 only, 1988."None>Marsden and Fahn (1988)</a>, <a href="#24" class="mim-tip-reference" title="Critchley, M. &lt;strong&gt;Remembering Kinnier Wilson.&lt;/strong&gt; Movement Disorders 3: 2-6, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3050469/&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;3050469&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/mds.870030102&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="3050469">Critchley (1988)</a>, <a href="#122" class="mim-tip-reference" title="Wilson, J. V. &lt;strong&gt;Memories of my father.&lt;/strong&gt; Movement Disorders 3: 7-9, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3050473/&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;3050473&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/mds.870030103&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="3050473">Wilson (1988)</a>, and <a href="#116" class="mim-tip-reference" title="Walshe, J. M. &lt;strong&gt;Wilson&#x27;s disease: yesterday, today, and tomorrow.&lt;/strong&gt; Movement Disorders 3: 10-29, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3050468/&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;3050468&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/mds.870030104&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="3050468">Walshe (1988)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3050469+3050468+3050473" 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="#117" class="mim-tip-reference" title="Walshe, J. M. &lt;strong&gt;Treatment of Wilson&#x27;s disease: the historical background.&lt;/strong&gt; Quart. J. Med. 89: 553-555, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8759497/&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;8759497&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/qjmed/89.7.553&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="8759497">Walshe (1996)</a> provided a review of the historical background of the treatment of Wilson disease, beginning with BAL, which had practical problems, and continuing with the chelating agent EDTA, which proved disappointing, and ending up with penicillamine (<a href="#115" class="mim-tip-reference" title="Walshe, J. M. &lt;strong&gt;Penicillamine, a new oral therapy for Wilson&#x27;s disease.&lt;/strong&gt; Am. J. Med. 21: 487-495, 1956.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13362281/&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;13362281&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9343(56)90066-3&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="13362281">Walshe, 1956</a>). Almost overnight, Wilson disease became one of the few inherited metabolic disorders for which there was effective therapy. So successful did this prove that the fact that zinc salts could block copper from the gut and could be of therapeutic value passed virtually unnoticed. <a href="#57" class="mim-tip-reference" title="Hoogenraad, T. U., van den Hamer, C. J. A. &lt;strong&gt;3 years of continuous oral zinc therapy in 4 patients with Wilson&#x27;s disease.&lt;/strong&gt; Acta Neurol. Scand. 67: 356-364, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6613522/&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;6613522&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1600-0404.1983.tb03153.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="6613522">Hoogenraad and van den Hamer (1983)</a> described its use. The third 'decoppering agent,' developed in the 1970s, was triethylene tetramine, as the dihydrochloride (Trientine). <a href="#117" class="mim-tip-reference" title="Walshe, J. M. &lt;strong&gt;Treatment of Wilson&#x27;s disease: the historical background.&lt;/strong&gt; Quart. J. Med. 89: 553-555, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8759497/&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;8759497&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/qjmed/89.7.553&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="8759497">Walshe (1996)</a> stated that a major and perhaps unexpected problem when initiating treatment is giving a 'reasonably accurate prognosis.' This may be related to the large number of different mutations and possible compound heterozygotes resulting in the varying clinical syndrome and different responses to treatment. He raised the question that initial deterioration seen in some patients after starting treatment may be due to free radical release in excess of the body's ability to remove them. He stated that the simultaneous administration of a free radical scavenger, such as alpha-tocopherol, might help eliminate the problem. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8759497+13362281+6613522" 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>See Also:</strong>
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<span class="mim-text-font">
<a href="#Anderson1960" class="mim-tip-reference" title="Anderson, P. J., Popper, H. &lt;strong&gt;Changes in hepatic structure in Wilson&#x27;s disease.&lt;/strong&gt; Am. J. Path. 36: 483-497, 1960.">Anderson and Popper (1960)</a>; <a href="#Bearn1972">Bearn (1972)</a>; <a href="#Carpenter1983" class="mim-tip-reference" title="Carpenter, T. O., Carnes, D. L., Anast, C. S. &lt;strong&gt;Hypoparathyroidism in Wilson&#x27;s disease.&lt;/strong&gt; New Eng. J. Med. 309: 873-877, 1983.">Carpenter et al. (1983)</a>; <a href="#Cartwright1978" class="mim-tip-reference" title="Cartwright, G. E. &lt;strong&gt;Diagnosis of treatable Wilson&#x27;s disease.&lt;/strong&gt; New Eng. J. Med. 298: 1347-1350, 1978.">Cartwright (1978)</a>; <a href="#Czlonkowska1981" class="mim-tip-reference" title="Czlonkowska, A., Rodo, M. &lt;strong&gt;Late onset of Wilson&#x27;s disease: report of a family.&lt;/strong&gt; Arch. Neurol. 38: 729-730, 1981.">Czlonkowska and Rodo (1981)</a>; <a href="#Dobyns1979" class="mim-tip-reference" title="Dobyns, W. B., Goldstein, N. P., Gordon, H. &lt;strong&gt;Clinical spectrum of Wilson&#x27;s disease (hepatolenticular degeneration).&lt;/strong&gt; Mayo Clin. Proc. 54: 35-42, 1979.">Dobyns et al. (1979)</a>; <a href="#Factor1982" class="mim-tip-reference" title="Factor, S. M., Cho, S., Sternlieb, I., Scheinberg, I. H., Goldfischer, S. &lt;strong&gt;The cardiomyopathy of Wilson&#x27;s disease: myocardial alterations in nine cases.&lt;/strong&gt; Virchows Arch. A Path. Anat. Histol. 397: 301-311, 1982.">Factor et al. (1982)</a>; <a href="#Forbes2000" class="mim-tip-reference" title="Forbes, J. R., Cox, D. W. &lt;strong&gt;Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.&lt;/strong&gt; Hum. Molec. Genet. 9: 1927-1935, 2000.">Forbes and Cox (2000)</a>; <a href="#Frommer1977" class="mim-tip-reference" title="Frommer, D., Morris, J., Sherlock, S., Abrams, J., Newman, S. &lt;strong&gt;Kayser-Fleischer-like rings in patients without Wilson&#x27;s disease.&lt;/strong&gt; Gastroenterology 72: 1331-1335, 1977.">Frommer et al. (1977)</a>; <a href="#Gadoth1980" class="mim-tip-reference" title="Gadoth, N., Liel, Y. &lt;strong&gt;Transient external ophthalmoplegia in Wilson&#x27;s disease.&lt;/strong&gt; Metab. Pediat. Ophthal. 4: 71-72, 1980.">Gadoth and Liel (1980)</a>; <a href="#Gibbs1979" class="mim-tip-reference" title="Gibbs, K., Walshe, J. M. &lt;strong&gt;A study of the ceruloplasmin concentrations found in 75 patients with Wilson&#x27;s disease, their kinships and various control groups.&lt;/strong&gt; Quart. J. Med. 48: 447-463, 1979.">Gibbs and Walshe (1979)</a>; <a href="#Goldstein1971" class="mim-tip-reference" title="Goldstein, N. P., Tauxe, W. N., McCall, J. T., Randall, R. V., Gross, J. B. &lt;strong&gt;Wilson&#x27;s disease (hepatolenticular degeneration): treatment with penicillamine and changes in hepatic trappings of radioactive copper.&lt;/strong&gt; Arch. Neurol. 24: 391-400, 1971.">Goldstein et al.
(1971)</a>; <a href="#Holtzman1967" class="mim-tip-reference" title="Holtzman, N. A., Naughton, M. A., Iber, F. L., Gaumnitz, B. M. &lt;strong&gt;Ceruloplasmin in Wilson&#x27;s disease.&lt;/strong&gt; J. Clin. Invest. 46: 993-1002, 1967.">Holtzman et al. (1967)</a>; <a href="#Levi1967" class="mim-tip-reference" title="Levi, A. J., Sherlock, S., Scheuer, P. J., Cumings, J. N. &lt;strong&gt;Presymptomatic Wilson&#x27;s disease.&lt;/strong&gt; Lancet 290: 575-579, 1967. Note: Originally Volume II.">Levi et al. (1967)</a>; <a href="#McAlpine1993" class="mim-tip-reference" title="McAlpine, P. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Winnipeg, Manitoba, Canada 11/12/1993.">McAlpine (1993)</a>; <a href="#Owen1982" class="mim-tip-reference" title="Owen, C. A., Jr., Ludwig, J. &lt;strong&gt;Inherited copper toxicosis in Bedlington terriers: Wilson&#x27;s disease (hepatolenticular degeneration).&lt;/strong&gt; Am. J. Path. 106: 432-434, 1982.">Owen and Ludwig (1982)</a>; <a href="#Saito1983" class="mim-tip-reference" title="Saito, T. &lt;strong&gt;Evaluation of segregation ratio in Wilson&#x27;s disease.&lt;/strong&gt; J. Med. Genet. 20: 271-275, 1983.">Saito (1983)</a>; <a href="#Saito1985" class="mim-tip-reference" title="Saito, T. &lt;strong&gt;An expected decrease in incidence of Wilson&#x27;s disease due to decrease in consanguinity.&lt;/strong&gt; Jpn. J. Hum. Genet. 30: 249-253, 1985.">Saito (1985)</a>; <a href="#Sasaki1994" class="mim-tip-reference" title="Sasaki, N., Hayashizaki, Y., Muramatsu, M., Matsuda, Y., Ando, Y., Kuramoto, T., Serikawa, T., Azuma, T., Naito, A., Agui, T., Yamashita, T., Miyoshi, I., Takeichi, N., Kasai, N. &lt;strong&gt;The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 202: 512-518, 1994.">Sasaki et al.
(1994)</a>; <a href="#Slovis1971" class="mim-tip-reference" title="Slovis, T. L., Dubois, R. S., Rodgerson, D. O., Silverman, A. &lt;strong&gt;The varied manifestations of Wilson&#x27;s disease.&lt;/strong&gt; J. Pediat. 78: 578-584, 1971.">Slovis et al. (1971)</a>; <a href="#Sternlieb1972" class="mim-tip-reference" title="Sternlieb, I., Scheinberg, I. H. &lt;strong&gt;Chronic hepatitis as a first manifestation of Wilson&#x27;s disease.&lt;/strong&gt; Ann. Intern. Med. 76: 59-64, 1972.">Sternlieb and Scheinberg (1972)</a>; <a href="#Strickland1973" class="mim-tip-reference" title="Strickland, G. T., Frommer, D., Leu, M. L., Pollard, R., Sherlock, S., Cumings, J. N. &lt;strong&gt;Wilson&#x27;s disease in the United Kingdom and Taiwan. I. General characteristics of 142 cases and prognosis. II. A genetic analysis of 88 cases.&lt;/strong&gt; Quart. J. Med. 42: 619-638, 1973.">Strickland et al. (1973)</a>; <a href="#Thomas1995" class="mim-tip-reference" title="Thomas, G. R., Roberts, E. A., Walshe, J. M., Cox, D. W. &lt;strong&gt;Haplotypes and mutations in Wilson disease.&lt;/strong&gt; Am. J. Hum. Genet. 56: 1315-1319, 1995.">Thomas et al. (1995)</a>; <a href="#Walshe1961" class="mim-tip-reference" title="Walshe, J. M., Cumings, J. N. &lt;strong&gt;Wilson&#x27;s Disease: Some Current Concepts.&lt;/strong&gt; Oxford: Blackwell (pub.) 1961. Pp. 1-292.">Walshe and Cumings
(1961)</a>; <a href="#Wilson1912" class="mim-tip-reference" title="Wilson, S. A. K. &lt;strong&gt;Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver.&lt;/strong&gt; Brain 34: 295-507, 1912.">Wilson (1912)</a>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
<a id="Alvarez2010" class="mim-anchor"></a>
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Alvarez, H. M., Xue, Y., Robinson, C. D., Canalizo-Hernandez, M. A., Marvin, R. G., Kelly, R. A., Mondragon, A., Penner-Hahn, J. E., O'Halloran, T. V.
<strong>Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation.</strong>
Science 327: 331-334, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19965379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19965379</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19965379[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=19965379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.1179907" target="_blank">Full Text</a>]
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<a id="Anderson1960" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Anderson, P. J., Popper, H.
<strong>Changes in hepatic structure in Wilson's disease.</strong>
Am. J. Path. 36: 483-497, 1960.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13793439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13793439</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13793439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="Azizi1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Azizi, E., Eshel, G., Aladjem, M.
<strong>Hypercalciuria and nephrolithiasis as a presenting sign in Wilson disease.</strong>
Europ. J. Pediat. 148: 548-549, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2744017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2744017</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2744017" 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/BF00441555" target="_blank">Full Text</a>]
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<a id="Bearn1958" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bearn, A. G., McKusick, V. A.
<strong>Azure lunulae: an unusual change in the fingernails in two patients with hepatolenticular degeneration (Wilson's disease).</strong>
J. Am. Med. Assoc. 166: 904-906, 1958.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13502081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13502081</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13502081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/jama.1958.62990080001010" target="_blank">Full Text</a>]
</p>
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<a id="Bearn1960" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bearn, A. G.
<strong>A genetical analysis of thirty families with Wilson's disease (hepatolenticular degeneration).</strong>
Ann. Hum. Genet. 24: 33-43, 1960.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13797909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13797909</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13797909" 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/j.1469-1809.1959.tb01713.x" target="_blank">Full Text</a>]
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<a id="Bearn1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bearn, A. G.
<strong>Wilson's disease.In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S. (eds.) : The Metabolic Basis of Inherited Disease. (3rd ed.)</strong>
New York: McGraw-Hill (pub.) 1972. Pp. 1033-1050.
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<a id="Bonne-Tamir1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bonne-Tamir, B., Farrer, L. A., Frydman, M., Kanaaneh, H.
<strong>Evidence for linkage between Wilson disease and esterase D in three kindreds: detection of linkage for an autosomal recessive disorder by the family study method.</strong>
Genet. Epidemiol. 3: 201-209, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3459695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3459695</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3459695" 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/gepi.1370030307" target="_blank">Full Text</a>]
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<a id="Bonne-Tamir1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bonne-Tamir, B., Farrer, L. A., Frydman, M., Kanani, C.
<strong>The locus for Wilson disease linked to esterase D in two Druze kindreds. (Abstract)</strong>
Am. J. Hum. Genet. 37: A47, 1985.
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Bonne-Tamir1990" class="mim-anchor"></a>
<div class="">
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Bonne-Tamir, B., Frydman, M., Agger, M. S., Bekeer, R., Bowcock, A. M., Hebert, J. M., Cavalli-Sforza, L. L., Farrer, L. A.
<strong>Wilson's disease in Israel: a genetic and epidemiological study.</strong>
Ann. Hum. Genet. 54: 155-168, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2382969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2382969</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2382969" 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/j.1469-1809.1990.tb00372.x" target="_blank">Full Text</a>]
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<a id="Bowcock1988" class="mim-anchor"></a>
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Bowcock, A. M., Farrer, L. A., Hebert, J. M., Agger, M., Sternlieb, I., Scheinberg, I. H., Buys, C. H. C. M., Scheffer, H., Frydman, M., Chajek-Saul, T., Bonne-Tamir, B., Cavalli-Sforza, L. L.
<strong>Eight closely linked loci place the Wilson disease locus within 13q14-q21.</strong>
Am. J. Hum. Genet. 43: 664-674, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3189332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3189332</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3189332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
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<a id="Brewer2006" class="mim-anchor"></a>
<div class="">
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Brewer, G. J., Askari, F., Lorincz, M. T., Carlson, M., Schilsky, M., Kluin, K. J., Hedera, P., Moretti, P., Fink, J. K., Tankanow, R., Dick, R. B., Sitterly, J.
<strong>Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease.</strong>
Arch. Neurol. 63: 521-527, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606763</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16606763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.63.4.521" target="_blank">Full Text</a>]
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<a id="Brewer1998" class="mim-anchor"></a>
<div class="">
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Brewer, G. J., Dick, R. D., Johnson, V. D., Brunberg, J. A., Kluin, K. J., Fink, J. K.
<strong>Treatment of Wilson's disease with zinc. XV. Long-term follow-up studies.</strong>
J. Lab. Clin. Med. 132: 264-278, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9794697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9794697</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9794697" 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/s0022-2143(98)90039-7" target="_blank">Full Text</a>]
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<a id="Brewer1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brewer, G. J., Dick, R. D., Yuzbasiyan-Gurkan, V., Johnson, V., Wang, Y.
<strong>Treatment of Wilson's disease with zinc XIII: therapy with zinc in presymptomatic patients from the time of diagnosis.</strong>
J. Lab. Clin. Med. 123: 849-858, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8201263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8201263</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8201263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="Brewer2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brewer, G. J., Hedera, P., Kluin, K. J., Carlson, M., Askari, F., Dick, R. B., Sitterly, J., Fink, J. K.
<strong>Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy.</strong>
Arch. Neurol. 60: 379-385, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12633149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12633149</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12633149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.60.3.379" target="_blank">Full Text</a>]
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<a id="Brewer1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brewer, G. J., Yuzbasiyan-Gurkan, V., Young, A. B.
<strong>The treatment of Wilson's disease.</strong>
Semin. Neurol. 7: 209-220, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3332455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3332455</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3332455" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1055/s-2008-1041420" target="_blank">Full Text</a>]
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<a id="Brewer1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brewer, G. J.
<strong>Penicillamine should not be used as initial therapy in Wilson's disease.</strong>
Mov. Disord. 14: 551-554, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10435490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10435490</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10435490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/1531-8257(199907)14:4&lt;551::aid-mds1002&gt;3.0.co;2-s" target="_blank">Full Text</a>]
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<a id="Buiakova1999" class="mim-anchor"></a>
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<p class="mim-text-font">
Buiakova, O. I., Xu, J., Lutsenko, S., Zeitlin, S., Das, K., Das, S., Ross, B. M., Mekios, C., Scheinberg, I. H., Gilliam, T. C.
<strong>Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation.</strong>
Hum. Molec. Genet. 8: 1665-1671, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441329</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/8.9.1665" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Bull1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W.
<strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong>
Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298639</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298639" 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/ng1293-327" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Carpenter1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Carpenter, T. O., Carnes, D. L., Anast, C. S.
<strong>Hypoparathyroidism in Wilson's disease.</strong>
New Eng. J. Med. 309: 873-877, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6888480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6888480</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6888480" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198310133091501" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Cartwright1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cartwright, G. E.
<strong>Diagnosis of treatable Wilson's disease.</strong>
New Eng. J. Med. 298: 1347-1350, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/349384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">349384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=349384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM197806152982406" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Chowrimootoo1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chowrimootoo, G. F. E., Scowcroft, H., Seymour, C. A.
<strong>Caeruloplasmin isoforms in Wilson's disease in neonates.</strong>
Arch. Dis. Child. Fetal Neonatal Ed. 79: F198-F201, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10194991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10194991</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10194991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/fn.79.3.f198" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Cossu1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cossu, P., Pirastu, M., Nucaro, A., Figus, A., Balestrieri, A., Borrone, C., Giacchino, R., Devoto, M., Monni, G., Cao, A.
<strong>Prenatal diagnosis of Wilson's disease by analysis of DNA polymorphism. (Letter)</strong>
New Eng. J. Med. 327: 57, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1350853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1350853</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1350853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM199207023270116" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Cox1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cox, D. W., Fraser, F. C., Sass-Kortsak, A.
<strong>A genetic study of Wilson's disease: evidence for heterogeneity.</strong>
Am. J. Hum. Genet. 24: 646-666, 1972.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5082916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5082916</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5082916" 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="24" class="mim-anchor"></a>
<a id="Critchley1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Critchley, M.
<strong>Remembering Kinnier Wilson.</strong>
Movement Disorders 3: 2-6, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3050469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3050469</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3050469" 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/mds.870030102" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="Czaja1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Czaja, M. J., Weiner, F. R., Schwarzenberg, S. J., Sternlieb, I., Scheinberg, I. H., Van Thiel, D. H., LaRusso, N. F., Giambrone, M.-A., Kirschner, R., Koschinsky, M. L., MacGillivray, R. T. A., Zern, M. A.
<strong>Molecular studies of ceruloplasmin deficiency in Wilson's disease.</strong>
J. Clin. Invest. 80: 1200-1204, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3654978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3654978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3654978" 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/JCI113180" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Czlonkowska1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Czlonkowska, A., Rodo, M.
<strong>Late onset of Wilson's disease: report of a family.</strong>
Arch. Neurol. 38: 729-730, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7305707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7305707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7305707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1981.00510110089019" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Danks1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Danks, D. M., Metz, G., Sewell, R., Prewett, E. J.
<strong>Wilson's disease in adults with cirrhosis but no neurological abnormalities.</strong>
Brit. Med. J. 301: 331-332, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2393743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2393743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2393743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/bmj.301.6747.331" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="De Bie2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
De Bie, P., Muller, P., Wijmenga, C., Klomp, L. W. J.
<strong>Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes.</strong>
J. Med. Genet. 44: 673-688, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17717039/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17717039</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17717039[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=17717039" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.2007.052746" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Devesa1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Devesa, R., Alvarez, A., de las Heras, G., de Miguel, J. R.
<strong>Wilson's disease treated with trientine during pregnancy.</strong>
J. Pediat. Gastroent. Nutr. 20: 102-103, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7884606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7884606</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7884606" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00005176-199501000-00018" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Dobyns1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dobyns, W. B., Goldstein, N. P., Gordon, H.
<strong>Clinical spectrum of Wilson's disease (hepatolenticular degeneration).</strong>
Mayo Clin. Proc. 54: 35-42, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/759736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">759736</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=759736" 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="31" class="mim-anchor"></a>
<a id="Factor1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Factor, S. M., Cho, S., Sternlieb, I., Scheinberg, I. H., Goldfischer, S.
<strong>The cardiomyopathy of Wilson's disease: myocardial alterations in nine cases.</strong>
Virchows Arch. A Path. Anat. Histol. 397: 301-311, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7157667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7157667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7157667" 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/BF00496571" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="32" class="mim-anchor"></a>
<a id="Farrer1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Farrer, L. A., Bonne-Tamir, B., Frydman, M., Magazanik, A., Kidd, K. K., Bowcock, A. M., Cavalli-Sforza, L. L.
<strong>Predicting genotypes at loci for autosomal recessive disorders using linked genetic markers: application to Wilson's disease.</strong>
Hum. Genet. 79: 109-117, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3164701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3164701</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3164701" 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/BF00280547" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Ferenci2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ferenci, P.
<strong>Regional distribution of mutations in the ATP7B gene in patients with Wilson disease: impact on genetic testing.</strong>
Hum. Genet. 120: 151-159, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16791614/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16791614</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16791614" 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/s00439-006-0202-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="Ferlan-Marolt1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ferlan-Marolt, V., Stepec, S.
<strong>Fulminant Wilsonian hepatitis unmasked by disease progression: report of a case and review of the literature.</strong>
Dig. Dis. Sci. 44: 1054-1058, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10235618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10235618</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10235618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1023/a:1026637403894" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="Figus1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others.
<strong>Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.</strong>
Am. J. Hum. Genet. 57: 1318-1324, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8533760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8533760</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8533760" 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="36" class="mim-anchor"></a>
<a id="Figus1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Figus, A., Lampis, R., Devoto, M., Ristaldi, M. S., Ideo, A., De Virgiliis, S., Nurchi, A. M., Corrias, A., Corda, R., Lai, M. E., Tocco, A., Deplano, A., Solinas, A., Zancan, L., Lee, W.-H., Cao, A., Pirastu, M., Balestrieri, A.
<strong>Carrier detection and early diagnosis of Wilson's disease by restriction fragment length polymorphism analysis.</strong>
J. Med. Genet. 26: 78-82, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2563776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2563776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2563776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.26.2.78" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Firneisz2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Firneisz, G., Woller, J., Ferenci, P., Szalay, F.
<strong>Postcremation diagnosis from an electric shaver.</strong>
Lancet 358: 34 only, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11454376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11454376</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11454376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="38" class="mim-anchor"></a>
<a id="Fitzgerald1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fitzgerald, M. A., Gross, J. B., Goldstein, N. P., Wahner, H. W., McCall, J. T.
<strong>Wilson's disease (hepatolenticular degeneration) of late adult onset: report of a case.</strong>
Mayo Clin. Proc. 50: 438-442, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1152537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1152537</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1152537" 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="39" class="mim-anchor"></a>
<a id="Forbes2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Forbes, J. R., Cox, D. W.
<strong>Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.</strong>
Hum. Molec. Genet. 9: 1927-1935, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/9.13.1927" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="40" class="mim-anchor"></a>
<a id="Foye2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Foye, P. M.
<strong>Postcremation diagnosis. (Letter)</strong>
Lancet 358: 1554 only, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11705608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11705608</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11705608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="41" class="mim-anchor"></a>
<a id="Frommer1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Frommer, D., Morris, J., Sherlock, S., Abrams, J., Newman, S.
<strong>Kayser-Fleischer-like rings in patients without Wilson's disease.</strong>
Gastroenterology 72: 1331-1335, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/558126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">558126</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=558126" 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="42" class="mim-anchor"></a>
<a id="Frydman1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Frydman, M., Bonne-Tamir, B., Farrer, L. A., Conneally, P. M., Magazanik, A., Ashbel, S., Goldwitch, Z.
<strong>Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase D locus.</strong>
Proc. Nat. Acad. Sci. 82: 1819-1821, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3856863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3856863</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3856863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.82.6.1819" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="43" class="mim-anchor"></a>
<a id="Gadoth1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gadoth, N., Liel, Y.
<strong>Transient external ophthalmoplegia in Wilson's disease.</strong>
Metab. Pediat. Ophthal. 4: 71-72, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7442347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7442347</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7442347" 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="44" class="mim-anchor"></a>
<a id="Garcia-Villarreal2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Garcia-Villarreal, L., Daniels, S., Shaw, S. H., Cotton, D., Galvin, M., Geskes, J., Bauer, P., Sierra-Hernandez, A., Buckler, A., Tugores, A.
<strong>High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.</strong>
Hepatology 32: 1329-1336, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11093740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11093740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11093740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1053/jhep.2000.20152" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="45" class="mim-anchor"></a>
<a id="Gibbs1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibbs, K., Walshe, J. M.
<strong>A study of the ceruloplasmin concentrations found in 75 patients with Wilson's disease, their kinships and various control groups.</strong>
Quart. J. Med. 48: 447-463, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/396544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">396544</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=396544" 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="46" class="mim-anchor"></a>
<a id="Goldstein1971" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goldstein, N. P., Tauxe, W. N., McCall, J. T., Randall, R. V., Gross, J. B.
<strong>Wilson's disease (hepatolenticular degeneration): treatment with penicillamine and changes in hepatic trappings of radioactive copper.</strong>
Arch. Neurol. 24: 391-400, 1971.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5554863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5554863</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5554863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1971.00480350025002" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="47" class="mim-anchor"></a>
<a id="Gow2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gow, P. J., Smallwood, R. A., Angus, P. W., Smith, A. L., Wall, A. J., Sewell, R. B.
<strong>Diagnosis of Wilson's disease: an experience over three decades.</strong>
Gut 46: 415-419, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10673307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10673307</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10673307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/gut.46.3.415" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="48" class="mim-anchor"></a>
<a id="Gromadzka2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gromadzka, G., Schmidt, H. H.-J., Genschel, J., Bochow, B., Rodo, M., Tarnacka, B., Litwin, T., Chabik, G., Czlonkowska, A.
<strong>Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.</strong>
Clin. Genet. 68: 524-532, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16283883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16283883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16283883" 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/j.1399-0004.2005.00528.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="49" class="mim-anchor"></a>
<a id="Gu2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gu, M., Cooper, J. M., Butler, P., Walker, A. P., Mistry, P. K., Dooley, J. S., Schapira, A. H. V.
<strong>Oxidative-phosphorylation defects in liver of patients with Wilson's disease.</strong>
Lancet 356: 469-474, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10981891/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10981891</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10981891" 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/s0140-6736(00)02556-3" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="50" class="mim-anchor"></a>
<a id="Guarino1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Guarino, M., Stracciari, A., D'Alessandro, R., Pazzaglia, P.
<strong>No neurological improvement after liver transplantation for Wilson's disease.</strong>
Acta Neurol. Scand. 92: 405-408, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8610495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8610495</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8610495" 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/j.1600-0404.1995.tb00155.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="51" class="mim-anchor"></a>
<a id="Gupta2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gupta, A., Aikath, D., Neogi, R., Datta, S., Basu, K., Maity, B., Trivedi, R., Ray, J., Das, S. K., Gangopadhyay, P. K., Ray, K.
<strong>Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype-phenotype correlation in Indian patients.</strong>
Hum. Genet. 118: 49-57, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16133174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16133174</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16133174" 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/s00439-005-0007-y" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="52" class="mim-anchor"></a>
<a id="Ha-Hao1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ha-Hao, D., Hefter, H., Stremmel, W., Castaneda-Guillot, C., Hernandez, A. H., Cox, D. W., Auburger, G.
<strong>His1069-to-gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.</strong>
Europ. J. Hum. Genet. 6: 616-623, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887381</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887381" 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/sj.ejhg.5200237" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="53" class="mim-anchor"></a>
<a id="Hartard1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hartard, C., Kunze, K.
<strong>Pregnancy in a patient with Wilson's disease treated with D-penicillamine and zinc sulfate: a case report and review of the literature.</strong>
Europ. Neurol. 34: 337-340, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7851456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7851456</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7851456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1159/000117074" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="54" class="mim-anchor"></a>
<a id="Hedera2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hedera, P., Brewer, G. J., Fink, J. K.
<strong>White matter changes in Wilson disease. (Letter)</strong>
Arch. Neurol. 59: 866-867, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12020274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12020274</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12020274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.59.5.866" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="55" class="mim-anchor"></a>
<a id="Hlubocka2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hlubocka, Z., Marecek, Z., Linhart, A., Kejrova, E., Pospisilova, L., Martasek, P., Aschermann, M.
<strong>Cardiac involvement in Wilson disease.</strong>
J. Inherit. Metab. Dis. 25: 269-277, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12227457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12227457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12227457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1023/a:1016546223327" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="56" class="mim-anchor"></a>
<a id="Holtzman1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Holtzman, N. A., Naughton, M. A., Iber, F. L., Gaumnitz, B. M.
<strong>Ceruloplasmin in Wilson's disease.</strong>
J. Clin. Invest. 46: 993-1002, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6026104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6026104</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6026104" 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/JCI105606" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="57" class="mim-anchor"></a>
<a id="Hoogenraad1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hoogenraad, T. U., van den Hamer, C. J. A.
<strong>3 years of continuous oral zinc therapy in 4 patients with Wilson's disease.</strong>
Acta Neurol. Scand. 67: 356-364, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6613522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6613522</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6613522" 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/j.1600-0404.1983.tb03153.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="58" class="mim-anchor"></a>
<a id="Hoogenraad1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hoogenraad, T. U.
<strong>Dangers of interrupting decoppering treatment in Wilson's disease. (Letter)</strong>
Arch. Neurol. 51: 972-973, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7945006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7945006</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7945006" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1994.00540220018005" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="59" class="mim-anchor"></a>
<a id="Hoppe1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hoppe, B., Neuhaus, T., Superti-Furga, A., Forster, I., Leumann, E.
<strong>Hypercalciuria and nephrocalcinosis, a feature of Wilson's disease.</strong>
Nephron 65: 460-462, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8290000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8290000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8290000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1159/000187530" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="60" class="mim-anchor"></a>
<a id="Houwen1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Houwen, R. H. J., Scheffer, H., te Meerman, G. J., van der Vlies, P., Buys, C. H. C. M.
<strong>Close linkage of the Wilson's disease locus to D13S12 in the chromosomal region 13q21 and not to ESD in 13q14.</strong>
Hum. Genet. 85: 560-562, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2227943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2227943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2227943" 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/BF00194238" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="61" class="mim-anchor"></a>
<a id="Huang1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Huang, L., Gitschier, J.
<strong>A novel gene involved in zinc transport is deficient in the lethal milk mouse.</strong>
Nature Genet. 17: 292-297, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354792</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9354792" 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/ng1197-292" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="62" class="mim-anchor"></a>
<a id="Hussain2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hussain, S. P., Raja, K., Amstad, P. A., Sawyer, M., Trudel, L. J., Wogan, G. N., Hofseth, L. J., Shields, P. G., Billiar, T. R., Trautwein, C., Hohler, T., Galle, P. R., Phillips, D. H., Markin, R., Marrogi, A. J., Harris, C. C.
<strong>Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: oxyradical overload diseases.</strong>
Proc. Nat. Acad. Sci. 97: 12770-12775, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11050162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11050162</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11050162[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=11050162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.220416097" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="63" class="mim-anchor"></a>
<a id="Jung2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jung, K.-H., Ahn, T.-B., Jeon, B. S.
<strong>Wilson disease with an initial manifestation of polyneuropathy.</strong>
Arch. Neurol. 62: 1628-1631, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16216950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16216950</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16216950" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.62.10.1628" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="64" class="mim-anchor"></a>
<a id="Kim1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kim, E. K., Yoo, O. J., Song, K. Y., Yoo, H. W., Choi, S. Y., Cho, S. W., Hahn, S. H.
<strong>Identification of three novel mutations and a high frequency of the arg778-to-leu mutation in Korean patients with Wilson disease.</strong>
Hum. Mutat. 11: 275-278, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554743" 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/(SICI)1098-1004(1998)11:4&lt;275::AID-HUMU4&gt;3.0.CO;2-L" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="65" class="mim-anchor"></a>
<a id="Kooy1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kooy, R. F., Van der Veen, A. Y., Verlind, E., Houwen, R. H. J., Scheffer, H., Buys, C. H. C. M.
<strong>Physical localisation of the chromosomal marker D13S31 places the Wilson disease locus at the junction of bands q14.3 and q21.1 of chromosome 13.</strong>
Hum. Genet. 91: 504-506, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8314565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8314565</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8314565" 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/BF00217780" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="66" class="mim-anchor"></a>
<a id="Kuan1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kuan, P.
<strong>Cardiac Wilson's disease.</strong>
Chest 91: 579-583, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3829752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3829752</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3829752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1378/chest.91.4.579" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="67" class="mim-anchor"></a>
<a id="Kuo1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kuo, Y.-M., Gitschier, J., Packman, S.
<strong>Developmental expression of the mouse mottled and toxic milk genes suggests distinct functions for the Menkes and Wilson disease copper transporters.</strong>
Hum. Molec. Genet. 6: 1043-1049, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9215673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9215673</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9215673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/6.7.1043" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="68" class="mim-anchor"></a>
<a id="Kuruvilla2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kuruvilla, A.
<strong>Postcremation diagnosis. (Letter)</strong>
Lancet 358: 1554 only, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11705607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11705607</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11705607" 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/S0140-6736(01)06610-7" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="69" class="mim-anchor"></a>
<a id="Lang1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lang, C. J. G., Rabas-Kolominsky, P., Engelhardt, A., Kobras, G., Konig, H. J.
<strong>Fatal deterioration of Wilson's disease after institution of oral zinc therapy. (Letter)</strong>
Arch. Neurol. 50: 1007-1008, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8280286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8280286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8280286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1993.00540100008005" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="70" class="mim-anchor"></a>
<a id="Lang2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lang, P. A., Schenck, M., Nicolay, J. P., Becker, J. U., Kempe, D. S., Lupescu, A., Koka, S., Eisele, K., Klarl, B. A., Rubben, H., Schmid, K. W., Mann, K., Hildenbrand, S., Hefter, H., Huber, S. M., Wieder, T., Erhardt, A., Haussinger, D., Gulbins, E., Lang, F.
<strong>Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide.</strong>
Nature Med. 13: 164-170, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17259995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17259995</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17259995" 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/nm1539" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="71" class="mim-anchor"></a>
<a id="Levi1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Levi, A. J., Sherlock, S., Scheuer, P. J., Cumings, J. N.
<strong>Presymptomatic Wilson's disease.</strong>
Lancet 290: 575-579, 1967. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4166824/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4166824</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4166824" 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/s0140-6736(67)90735-0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="72" class="mim-anchor"></a>
<a id="LeWitt1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
LeWitt, P. A.
<strong>Penicillamine as a controversial treatment for Wilson's disease. (Editorial)</strong>
Mov. Disord. 14: 555-556, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10435491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10435491</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10435491" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/1531-8257(199907)14:4&lt;555::aid-mds1003&gt;3.0.co;2-l" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="73" class="mim-anchor"></a>
<a id="Li1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Li, Y., Togashi, Y., Sato, S., Emoto, T., Kang, J.-H., Takeichi, N., Kobayashi, H., Kojima, Y., Une, Y., Uchino, J.
<strong>Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis: a model of Wilson's disease.</strong>
J. Clin. Invest. 87: 1858-1861, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022751</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2022751" 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/JCI115208" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="74" class="mim-anchor"></a>
<a id="Lingam1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lingam, S., Wilson, J., Nazer, H., Mowat, A. P.
<strong>Neurological abnormalities in Wilson's disease are reversible.</strong>
Neuropediatrics 18: 11-12, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3561699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3561699</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3561699" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1055/s-2008-1052427" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="75" class="mim-anchor"></a>
<a id="Litin1959" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Litin, R. B., Randall, R. V., Goldstein, N. P., Power, M. H., Diessner, G. R.
<strong>Hypercalciuria in hepatolenticular degeneration (Wilson's disease).</strong>
Am. J. Med. Sci. 238: 614-620, 1959.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14417517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14417517</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14417517" 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="76" class="mim-anchor"></a>
<a id="Loudianos1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Figus, A., Lilliu, F., De Virgiliis, S., Nurchi, A. M., Deplano, A., Moi, P., Pirastu, M., Cao, A.
<strong>Molecular characterization of Wilson disease in the Sardinian population--evidence of a founder effect.</strong>
Hum. Mutat. 14: 294-303, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502776" 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/(SICI)1098-1004(199910)14:4&lt;294::AID-HUMU4&gt;3.0.CO;2-9" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="77" class="mim-anchor"></a>
<a id="Loudianos1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Nurchi, A., Sturniolo, G. C., Marcellini, M., Zancan, L., Bragetti, P., Akar, N., Yagci, R., Vegnente, A., Cao, A., Pirastu, M.
<strong>Further delineation of the molecular pathology of Wilson disease in the Mediterranean population.</strong>
Hum. Mutat. 12: 89-94, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9671269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9671269</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9671269" 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/(SICI)1098-1004(1998)12:2&lt;89::AID-HUMU3&gt;3.0.CO;2-G" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="78" class="mim-anchor"></a>
<a id="Mak2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Mak, C. M., Lam, C.-W., Tam, S., Lai, C.-L., Chan, L.-Y., Fan, S.-T., Lau, Y.-L., Lai, S.-T., Yuen, P., Hui, J., Fu, C.-C., Wong, K.-S., and 13 others.
<strong>Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: identification of 17 novel mutations and its genetic heterogeneity.</strong>
J. Hum. Genet. 53: 55-63, 2008. Note: Erratum: J. Hum. Genet. 53: 375 only, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18034201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18034201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18034201" 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/s10038-007-0218-2" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="79" class="mim-anchor"></a>
<a id="Margarit2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Margarit, E., Bach, V., Gomez, D., Bruguera, M., Jara, P., Queralt, R., Ballesta, F.
<strong>Mutation analysis of Wilson disease in the Spanish population--identification of a prevalent substitution and eight novel mutations in the ATP7B gene.</strong>
Clin. Genet. 68: 61-68, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15952988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15952988</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15952988" 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/j.1399-0004.2005.00439.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="80" class="mim-anchor"></a>
<a id="Marsden1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Marsden, C. D., Fahn, S.
<strong>Dr. S. A. Kinnier Wilson (1878-1937). (Editorial)</strong>
Mov. Disord. 3: 1 only, 1988.
</p>
</div>
</li>
<li>
<a id="81" class="mim-anchor"></a>
<a id="McAlpine1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McAlpine, P.
<strong>Personal Communication.</strong>
Winnipeg, Manitoba, Canada 11/12/1993.
</p>
</div>
</li>
<li>
<a id="82" class="mim-anchor"></a>
<a id="Menerey1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Menerey, K. A., Eider, W., Brewer, G. J., Braunstein, E. M., Schumacher, H. R., Fox, I. H.
<strong>The arthropathy of Wilson's disease: clinical and pathologic features.</strong>
J. Rheum. 15: 331-337, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3361541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3361541</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3361541" 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="83" class="mim-anchor"></a>
<a id="Okada2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Okada, T., Shiono, Y., Hayashi, H., Satoh, H., Sawada, T., Suzuki, A., Takeda, Y., Yano, M., Michitaka, K., Onji, M., Mabuchi, H.
<strong>Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.</strong>
Hum. Mutat. 15: 454-462, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790207" 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/(SICI)1098-1004(200005)15:5&lt;454::AID-HUMU7&gt;3.0.CO;2-J" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="84" class="mim-anchor"></a>
<a id="Olivarez2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Olivarez, L., Caggana, M., Pass, K. A., Ferguson, P., Brewer, G. J.
<strong>Estimate of the frequency of Wilson's disease in the US Caucasian population: a mutation analysis approach.</strong>
Ann. Hum. Genet. 65: 459-463, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11806854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11806854</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11806854" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1017/S0003480001008764" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="85" class="mim-anchor"></a>
<a id="Owen1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Owen, C. A., Jr., Ludwig, J.
<strong>Inherited copper toxicosis in Bedlington terriers: Wilson's disease (hepatolenticular degeneration).</strong>
Am. J. Path. 106: 432-434, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7065120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7065120</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7065120" 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="86" class="mim-anchor"></a>
<a id="Park2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Park, H.-D., Ki, C.-S., Lee, S.-Y., Kim, J.-W.
<strong>Carrier frequency of the R778L, A874V, and N1270S mutations in the ATP7B gene in a Korean population. (Letter)</strong>
Clin. Genet. 75: 405-407, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19419418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19419418</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19419418" 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/j.1399-0004.2008.01132.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="87" class="mim-anchor"></a>
<a id="Park2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Park, S., Park, J.-Y., Kim, G.-H., Choi, J.-H., Kim, K.-M., Kim, J.-B., Yoo, H.-W.
<strong>Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease.</strong>
Hum. Mutat. 28: 1108-1113, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17587212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17587212</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17587212" 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/humu.20574" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="88" class="mim-anchor"></a>
<a id="Passwell1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Passwell, J., Adam, A., Garfinkel, D., Streiffler, M., Cohen, B. E.
<strong>Heterogeneity of Wilson's disease in Israel.</strong>
Isr. J. Med. Sci. 13: 15-19, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/838566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">838566</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=838566" 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="89" class="mim-anchor"></a>
<a id="Petrukhin1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Petrukhin, K., Fischer, S. G., Pirastu, M., Tanzi, R. E., Chernov, I., Devoto, M., Brzustowicz, L. M., Cayanis, E., Vitale, E., Russo, J. J., Matseoane, D., Boukhgalter, B., Wasco, W., Figus, A. L., Loudianos, J., Cao, A., Sternlieb, I., Evgrafov, O., Parano, E., Pavone, L., Warburton, D., Ott, J., Penchaszadeh, G. K., Scheinberg, I. H., Gilliam, T. C.
<strong>Mapping, cloning and genetic characterization of the region containing the Wilson disease gene.</strong>
Nature Genet. 5: 338-343, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298640</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298640" 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/ng1293-338" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="90" class="mim-anchor"></a>
<a id="Polson1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Polson, R. J., Rolles, K., Calne, R. Y., Williams, R., Marsden, D.
<strong>Reversal of severe neurological manifestations of Wilson's disease following orthotopic liver transplantation.</strong>
Quart. J. Med. 64: 685-691, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3328213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3328213</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3328213" 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="91" class="mim-anchor"></a>
<a id="Ross1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ross, M. E., Jacobson, I. M., Dienstag, J. L., Martin, J. B.
<strong>Late-onset Wilson's disease with neurological involvement in the absence of Kayser-Fleischer rings.</strong>
Ann. Neurol. 17: 411-413, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4004163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4004163</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4004163" 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/ana.410170421" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="92" class="mim-anchor"></a>
<a id="Saito1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Saito, T.
<strong>Evaluation of segregation ratio in Wilson's disease.</strong>
J. Med. Genet. 20: 271-275, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6620327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6620327</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6620327" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.20.4.271" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="93" class="mim-anchor"></a>
<a id="Saito1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Saito, T.
<strong>An expected decrease in incidence of Wilson's disease due to decrease in consanguinity.</strong>
Jpn. J. Hum. Genet. 30: 249-253, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3834206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3834206</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3834206" 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/BF01876476" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="94" class="mim-anchor"></a>
<a id="Sasaki1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sasaki, N., Hayashizaki, Y., Muramatsu, M., Matsuda, Y., Ando, Y., Kuramoto, T., Serikawa, T., Azuma, T., Naito, A., Agui, T., Yamashita, T., Miyoshi, I., Takeichi, N., Kasai, N.
<strong>The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene.</strong>
Biochem. Biophys. Res. Commun. 202: 512-518, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8037756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8037756</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8037756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1006/bbrc.1994.1958" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="95" class="mim-anchor"></a>
<a id="Scheffer1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Scheffer, H., Houwen, R. H. J., Te Meerman, G. J., Loessner, J., Bachmann, B., Kunert, E., Verlind, E., Buys, C. H. C. M.
<strong>Identification of crossovers in Wilson disease families as reference points for a genetic localization of the gene.</strong>
Hum. Genet. 89: 607-611, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1511977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1511977</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1511977" 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/BF00221947" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="96" class="mim-anchor"></a>
<a id="Shokeir1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shokeir, M. H. K., Shreffler, D. C.
<strong>Cytochrome oxidase deficiency in Wilson's disease: a suggested ceruloplasmin function.</strong>
Proc. Nat. Acad. Sci. 62: 867-872, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4308098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4308098</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4308098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.62.3.867" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="97" class="mim-anchor"></a>
<a id="Shokeir1971" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shokeir, M. H. K.
<strong>Investigations on the nature of ceruloplasmin deficiency in the newborn.</strong>
Clin. Genet. 2: 223-227, 1971.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5004412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5004412</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5004412" 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/j.1399-0004.1971.tb00281.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="98" class="mim-anchor"></a>
<a id="Slovis1971" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Slovis, T. L., Dubois, R. S., Rodgerson, D. O., Silverman, A.
<strong>The varied manifestations of Wilson's disease.</strong>
J. Pediat. 78: 578-584, 1971.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5547815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5547815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5547815" 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/s0022-3476(71)80458-4" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="99" class="mim-anchor"></a>
<a id="Sokol1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sokol, R. J., Francis, P. D., Gold, S. H., Ford, D. M., Lum, G. M., Ambruso, D. R.
<strong>Orthotopic liver transplantation for acute fulminant Wilson disease.</strong>
J. Pediat. 107: 549-552, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3900322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3900322</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3900322" 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/s0022-3476(85)80016-0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="100" class="mim-anchor"></a>
<a id="Starosta-Rubinstein1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Starosta-Rubinstein, S., Young, A. B., Kluin, K., Hill, G., Aisen, A. M., Gabrielsen, T., Brewer, G. J.
<strong>Clinical assessment of 31 patients with Wilson's disease: correlations with structural changes on magnetic resonance imaging.</strong>
Arch. Neurol. 44: 365-370, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3827691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3827691</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3827691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1987.00520160007005" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="101" class="mim-anchor"></a>
<a id="Sternlieb1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sternlieb, I., Scheinberg, I. H.
<strong>Chronic hepatitis as a first manifestation of Wilson's disease.</strong>
Ann. Intern. Med. 76: 59-64, 1972.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5021554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5021554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5021554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.7326/0003-4819-76-1-59" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="102" class="mim-anchor"></a>
<a id="Strickland1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Strickland, G. T., Frommer, D., Leu, M. L., Pollard, R., Sherlock, S., Cumings, J. N.
<strong>Wilson's disease in the United Kingdom and Taiwan. I. General characteristics of 142 cases and prognosis. II. A genetic analysis of 88 cases.</strong>
Quart. J. Med. 42: 619-638, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4199472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4199472</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4199472" 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="103" class="mim-anchor"></a>
<a id="Takeshita2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Takeshita, Y., Shimizu, N., Yamaguchi, Y., Nakazono, H., Saitou, M., Fujikawa, Y., Aoki, T.
<strong>Two families with Wilson disease in which siblings showed different phenotypes.</strong>
J. Hum. Genet. 47: 543-547, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376745" 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/s100380200082" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="104" class="mim-anchor"></a>
<a id="Tanzi1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C.
<strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong>
Nature Genet. 5: 344-350, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8298641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8298641</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8298641" 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/ng1293-344" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="105" class="mim-anchor"></a>
<a id="Terada1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Terada, K., Nakako, T., Yang, X.-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., Sugiyama, T.
<strong>Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.</strong>
J. Biol. Chem. 273: 1815-1820, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9430732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9430732</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9430732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1074/jbc.273.3.1815" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="106" class="mim-anchor"></a>
<a id="Theophilos1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Theophilos, M. B., Cox, D. W., Mercer, J. F. B.
<strong>The toxic milk mouse is a murine model of Wilson disease.</strong>
Hum. Molec. Genet. 5: 1619-1624, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8894697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8894697</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8894697" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/5.10.1619" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="107" class="mim-anchor"></a>
<a id="Thomas1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Thomas, G. R., Bull, P. C., Roberts, E. A., Walshe, J. M., Cox, D. W.
<strong>Haplotype studies in Wilson disease.</strong>
Am. J. Hum. Genet. 54: 71-78, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8279472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8279472</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8279472" 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="108" class="mim-anchor"></a>
<a id="Thomas1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W.
<strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong>
Nature Genet. 9: 210-217, 1995. Note: Erratum:. Nature Genet. 9: 451 only, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7626145" 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/ng0295-210" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="109" class="mim-anchor"></a>
<a id="Thomas1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Thomas, G. R., Jensson, O., Gudmundsson, G., Thorsteinsson, L., Cox, D. W.
<strong>Wilson disease in Iceland: a clinical and genetic study.</strong>
Am. J. Hum. Genet. 56: 1140-1146, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726170" 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="110" class="mim-anchor"></a>
<a id="Thomas1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Thomas, G. R., Roberts, E. A., Walshe, J. M., Cox, D. W.
<strong>Haplotypes and mutations in Wilson disease.</strong>
Am. J. Hum. Genet. 56: 1315-1319, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762553</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762553" 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="111" class="mim-anchor"></a>
<a id="van de Sluis1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
van de Sluis, B. J. A., Breen, M., Nanji, M., van Wolferen, M., de Jong, P., Binns, M. M., Pearson, P. L., Kuipers, J., Rothuizen, J., Cox, D. W., Wijmenga, C., van Oost, B. A.
<strong>Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13-p16.</strong>
Hum. Molec. Genet. 8: 501-507, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9949209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9949209</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9949209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/8.3.501" target="_blank">Full Text</a>]
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<a id="112" class="mim-anchor"></a>
<a id="van Wassenaer-van Hall1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
van Wassenaer-van Hall, H. N., van den Heuvel, A. G., Jansen, G. H., Hoogenraad, T. U., Mali, W. P. T. M.
<strong>Cranial MR in Wilson disease: abnormal white matter in extrapyramidal and pyramidal tracts.</strong>
Am. J. Neuroradiol. 16: 2021-2027, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8585490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8585490</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8585490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="113" class="mim-anchor"></a>
<a id="Wallace2020" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wallace, D. F., Dooley, J. S.
<strong>ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.</strong>
Hum. Genet. 139: 1065-1075, 2020.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32248359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32248359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32248359" 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/s00439-020-02161-3" target="_blank">Full Text</a>]
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<a id="114" class="mim-anchor"></a>
<a id="Walshe1961" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Walshe, J. M., Cumings, J. N.
<strong>Wilson's Disease: Some Current Concepts.</strong>
Oxford: Blackwell (pub.) 1961. Pp. 1-292.
</p>
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</li>
<li>
<a id="115" class="mim-anchor"></a>
<a id="Walshe1956" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Walshe, J. M.
<strong>Penicillamine, a new oral therapy for Wilson's disease.</strong>
Am. J. Med. 21: 487-495, 1956.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13362281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13362281</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13362281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0002-9343(56)90066-3" target="_blank">Full Text</a>]
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<a id="116" class="mim-anchor"></a>
<a id="Walshe1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Walshe, J. M.
<strong>Wilson's disease: yesterday, today, and tomorrow.</strong>
Movement Disorders 3: 10-29, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3050468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3050468</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3050468" 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/mds.870030104" target="_blank">Full Text</a>]
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<a id="117" class="mim-anchor"></a>
<a id="Walshe1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Walshe, J. M.
<strong>Treatment of Wilson's disease: the historical background.</strong>
Quart. J. Med. 89: 553-555, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8759497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8759497</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8759497" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/qjmed/89.7.553" target="_blank">Full Text</a>]
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<a id="118" class="mim-anchor"></a>
<a id="Walshe1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Walshe, J. M.
<strong>Penicillamine: the treatment of first choice for patients with Wilson's disease.</strong>
Mov. Disord. 14: 545-550, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10435489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10435489</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10435489" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/1531-8257(199907)14:4&lt;545::aid-mds1001&gt;3.0.co;2-u" target="_blank">Full Text</a>]
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<a id="Wang2011" class="mim-anchor"></a>
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Wang, L.-H., Huang, Y.-Q., Shang, X., Su, Q.-X., Xiong, F., Yu, Q.-Y., Lin, H.-P., Wei, Z.-S., Hong, M.-F., Xu, X.-M.
<strong>Mutation analysis of 73 southern Chinese Wilson's disease patients: identification of 10 novel mutations and its clinical correlation.</strong>
J. Hum. Genet. 56: 660-665, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21796144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21796144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21796144" 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/jhg.2011.76" target="_blank">Full Text</a>]
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<a id="120" class="mim-anchor"></a>
<a id="Whelton1968" class="mim-anchor"></a>
<div class="">
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Whelton, M. J., Pope, F. M.
<strong>Azure lunules in argyria: corneal changes resembling Kayser-Fleischer rings.</strong>
Arch. Intern. Med. 121: 267-269, 1968.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5642746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5642746</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5642746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="121" class="mim-anchor"></a>
<a id="Wiebers1979" class="mim-anchor"></a>
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Wiebers, D. O., Wilson, D. M., McLeod, R. A., Goldstein, N. P.
<strong>Renal stones in Wilson's disease.</strong>
Am. J. Med. 67: 249-254, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/463930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">463930</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=463930" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0002-9343(79)90399-1" target="_blank">Full Text</a>]
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<a id="122" class="mim-anchor"></a>
<a id="Wilson1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wilson, J. V.
<strong>Memories of my father.</strong>
Movement Disorders 3: 7-9, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3050473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3050473</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3050473" 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/mds.870030103" target="_blank">Full Text</a>]
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<a id="123" class="mim-anchor"></a>
<a id="Wilson1912" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wilson, S. A. K.
<strong>Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver.</strong>
Brain 34: 295-507, 1912.
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<a id="124" class="mim-anchor"></a>
<a id="Wu1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wu, J., Forbes, J. R., Chen, H. S., Cox, D. W.
<strong>The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene.</strong>
Nature Genet. 7: 541-545, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951327</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951327" 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/ng0894-541" target="_blank">Full Text</a>]
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<a id="Wu2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wu, Z.-Y., Lin, M.-T., Murong, S.-X., Wang, N.
<strong>Molecular diagnosis and prophylactic therapy for presymptomatic Chinese patients with Wilson disease.</strong>
Arch. Neurol. 60: 737-741, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12756138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12756138</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12756138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.60.5.737" target="_blank">Full Text</a>]
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<a id="126" class="mim-anchor"></a>
<a id="Yuzbasiyan-Gurkan1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Yuzbasiyan-Gurkan, V., Brewer, G. J., Boerwinkle, E., Venta, P. J.
<strong>Linkage of the Wilson disease gene to chromosome 13 in North-American pedigrees.</strong>
Am. J. Hum. Genet. 42: 825-829, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3163469/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3163469</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3163469" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="127" class="mim-anchor"></a>
<a id="Yuzbasiyan-Gurkan1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Yuzbasiyan-Gurkan, V., Wagnitz, S., Blanton, S. H., Brewer, G. J.
<strong>Linkage studies of the esterase D and retinoblastoma genes to canine copper toxicosis: a model for Wilson disease.</strong>
Genomics 15: 86-90, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1006/geno.1993.1013" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 02/03/2021
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Cassandra L. Kniffin - updated : 11/1/2011<br>Cassandra L. Kniffin - updated : 12/22/2010<br>Ada Hamosh - updated : 2/1/2010<br>Marla J. F. O'Neill - updated : 11/18/2008<br>Cassandra L. Kniffin - updated : 1/2/2008<br>Cassandra L. Kniffin - updated : 11/14/2007<br>Marla J. F. O'Neill - updated : 4/12/2007<br>Cassandra L. Kniffin - updated : 3/21/2007<br>Cassandra L. Kniffin - updated : 2/6/2007<br>Cassandra L. Kniffin - updated : 11/2/2006<br>Marla J. F. O'Neill - updated : 10/25/2006<br>Cassandra L. Kniffin - updated : 6/9/2006<br>Marla J. F. O'Neill - updated : 12/28/2005<br>Marla J. F. O'Neill - updated : 7/5/2005<br>Ada Hamosh - updated : 10/8/2003<br>Ada Hamosh - updated : 7/8/2003<br>Cassandra L. Kniffin - updated : 6/2/2003<br>Victor A. McKusick - updated : 3/6/2003<br>Victor A. McKusick - updated : 1/7/2003<br>Cassandra L. Kniffin - updated : 12/9/2002<br>Cassandra L. Kniffin - reorganized : 4/29/2002<br>Cassandra L. Kniffin - updated : 4/29/2002<br>Deborah L. Stone - updated : 3/22/2002<br>Victor A. McKusick - updated : 3/7/2002<br>Victor A. McKusick - updated : 2/8/2002<br>George E. Tiller - updated : 4/24/2001<br>Victor A. McKusick - updated : 11/30/2000<br>George E. Tiller - updated : 10/25/2000<br>Ada Hamosh - updated : 10/4/2000<br>Ada Hamosh - updated : 9/13/2000<br>Victor A. McKusick - updated : 5/19/2000<br>Paul Brennan - updated : 5/3/2000<br>Victor A. McKusick - updated : 3/24/2000<br>Paul Brennan - updated : 2/21/2000<br>Victor A. McKusick - updated : 2/1/2000<br>Wilson H. Y. Lo - updated : 11/17/1999<br>Victor A. McKusick - updated : 10/13/1999<br>Sonja A. Rasmussen - updated : 6/30/1999<br>Victor A. McKusick - updated : 6/11/1999<br>Victor A. McKusick - updated : 4/7/1999<br>Victor A. McKusick - updated : 3/17/1999<br>Victor A. McKusick - updated : 9/18/1998<br>Victor A. McKusick - updated : 8/5/1998<br>Victor A. McKusick - updated : 4/29/1998<br>Victor A. McKusick - updated : 10/27/1997<br>Victor A. McKusick - updated : 8/15/1997<br>Moyra Smith - updated : 12/16/1996<br>Orest Hurko - updated : 3/6/1996<br>Alan F. Scott - updated : 9/27/1995<br>Orest Hurko - updated : 9/21/1995
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Victor A. McKusick : 6/4/1986
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alopez : 09/23/2024
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<strong>#</strong> 277900
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WILSON DISEASE; WND
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<em>Alternative titles; symbols</em>
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WD<br />
HEPATOLENTICULAR DEGENERATION
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<strong>SNOMEDCT:</strong> 190823004, 88518009; &nbsp;
<strong>ICD10CM:</strong> E83.01; &nbsp;
<strong>ORPHA:</strong> 905; &nbsp;
<strong>DO:</strong> 893; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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13q14.3
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Wilson disease
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277900
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Autosomal recessive
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3
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ATP7B
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606882
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that Wilson disease (WND) is caused by homozygous or compound heterozygous mutation in the ATP7B gene (606882) on chromosome 13q14.</p>
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<strong>Description</strong>
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<p>Wilson disease (WND) is an autosomal recessive disorder characterized by dramatic build-up of intracellular hepatic copper with subsequent hepatic and neurologic abnormalities.</p><p>De Bie et al. (2007) provided a detailed review of the molecular pathogenesis of Wilson disease. </p>
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<strong>Clinical Features</strong>
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<p>In Wilson disease, the basal ganglia and liver undergo changes that express themselves in neurologic manifestations and signs of cirrhosis, respectively. A disturbance in copper metabolism is somehow involved in the mechanism. Low ceruloplasmin (117700) is found in the serum. Shokeir and Shreffler (1969) advanced the hypothesis that ceruloplasmin functions in enzymatic transfer of copper to copper-containing enzymes such as cytochrome oxidase. Supporting the hypothesis was the finding of markedly reduced levels of activity of cytochrome oxidase in Wilson disease and moderate reductions in heterozygotes. </p><p>The Kayser-Fleischer ring is a deep copper-colored ring at the periphery of the cornea which is frequently found in Wilson disease and is thought to represent copper deposits. Bearn and McKusick (1958) and Whelton and Pope (1968) described azure lunulae of the fingernails in patients with Wilson disease. These are presumably of the same significance as the Kayser-Fleischer ring and possibly arise by the same mechanism. Hypercalciuria and nephrocalcinosis are not uncommon in patients with Wilson disease. Hypercalciuria associated with this disorder was first reported by Litin et al. (1959). Wiebers et al. (1979) observed renal stones in 7 of 54 patients with Wilson disease. Penicillamine therapy was accompanied by a decrease in urinary calcium excretion to normal values in 3 patients, but hypercalciuria persisted in 3. Azizi et al. (1989) described hypercalciuria and nephrolithiasis as presenting signs in Wilson disease and postulated tubular defect in calcium reabsorption. Hoppe et al. (1993) described a 17-year-old male with a 6-year history of hypercalciuria, nephrocalcinosis, and nephrolithiasis, in whom Wilson disease was finally diagnosed. </p><p>Bearn (1960) suggested that Jewish WND patients from eastern Europe are different from other groups of patients in that the age at onset is later, the disease is generally milder, and the serum copper and serum ceruloplasmin levels are 'particularly liable to be of normal concentration.' Bonne-Tamir et al. (1990) provided a full analysis of Wilson disease in Israel. </p><p>From a study of 28 Canadian families, Cox et al. (1972) suggested that there are at least 3 forms of Wilson disease. In a rare 'atypical form,' the heterozygotes show about 50% of the normal level of ceruloplasmin. This gene may have been of German-Mennonite derivation. In the 2 typical forms heterozygotes have normal ceruloplasmin levels, although they can be identified by decreased reappearance of radioactive copper into serum and ceruloplasmin. The authors referred to the 2 'typical forms' as the Slavic and the juvenile type. The Slavic type has a late age of onset and is predominantly a neurologic disease. The juvenile type, which occurs in western Europeans and several other ethnic groups, has onset before age 16 years and is frequently a hepatic disease. Czaja et al. (1987) demonstrated reduced ceruloplasmin gene transcription in 4 patients with Wilson disease (44% of controls). Low levels of ceruloplasmin are a normal finding in the newborn (Shokeir, 1971). </p><p>In Israel, Passwell et al. (1977) observed that Arab patients show an earlier age of onset and more severe course than Jewish patients. Within families of both ethnic groups, age of onset and type of disease show a close correlation. Thus, the authors concluded that the interethnic differences may reflect different mutations. </p><p>Fitzgerald et al. (1975) described a 57-year-old man with liver disease that they concluded represented Wilson disease. Ross et al. (1985) described a patient who was found to have hepatosplenomegaly at age 51, developed hand tremor at 52, and was having difficulty with hand dexterity at 55. The diagnosis of Wilson disease was made at age 58 on the basis of urinary, serum, and hepatic copper studies and liver histology, and despite the absence of Kayser-Fleischer rings. Wilson disease is not generally considered in patients over 30 years of age who present with liver disease and without neurologic signs. Danks et al. (1990) reported 4 such cases: 2 men, aged 43 and 48, and 2 women, aged 44 and 58. The 58-year-old woman had been ill for only 1 week and died in 36 hours of acute hepatorenal failure. Her sister had died of cirrhosis and liver failure at age 28. Alcohol intake was minimal or completely avoided in all. None of the known hepatitis viruses could be identified and no autoantibodies were detected. </p><p>Kuan (1987) demonstrated manifestations of myocardial involvement in Wilson disease. The occurrence of chondrocalcinosis and osteoarthritis in Wilson disease may be due to copper accumulation similar to the arthropathy of hemochromatosis (HFE; 235200) (Menerey et al., 1988). </p><p>Starosta-Rubinstein et al. (1987) correlated clinical manifestations with the findings of magnetic resonance imaging (MRI) of the brain. Van Wassenaer-van Hall et al. (1995) also used cranial MRI to study WND patients. Although the most striking findings on their MRI scan were abnormalities of the basal ganglia in generalized cerebral atrophy, they also noted subtle white matter abnormalities in some WND patients, particularly at the dentatorubrothalamic, pontocerebellar, and corticospinal tracts. </p><p>From Slovenia, Ferlan-Marolt and Stepec (1999) reported a 24-year-old woman with fulminant Wilsonian hepatitis accompanied by hemolytic anemia and leading to death in a few weeks. Kayser-Fleischer rings were said to have been absent, and there were no neurologic abnormalities until the development of the flapping tremor of hepatic failure in the last days of life. </p><p>Gu et al. (2000) studied mitochondrial function and aconitase activity in Wilson disease liver tissue and compared the results with those in a series of healthy controls and patients without Wilson disease. There was evidence of severe mitochondrial dysfunction in the livers of patients with Wilson disease. Enzyme activities were decreased as follows: complex I by 62%, complex II+III by 52%, complex IV by 33%, and aconitase by 71%. These defects did not seem to be secondary to penicillamine use, cholestasis, or poor hepatocellular synthetic function. Gu et al. (2000) stated that the pattern of enzyme defects suggests that free radical formation and oxidative damage, probably mediated via mitochondrial copper accumulation, are important in Wilson disease pathogenesis, and that their results provide a rationale for a study of the use of antioxidants in Wilson disease. </p><p>Both Wilson disease and hemochromatosis (235200), characterized by excess hepatic deposition of iron and copper, respectively, produce oxidative stress and increase the risk of liver cancer. Because the frequency of p53 mutated alleles (191170) in nontumorous human tissue may be a biomarker of oxyradical damage and identify individuals at increased cancer risk, Hussain et al. (2000) determined the frequency of p53 mutated alleles in nontumorous liver tissue from WND and hemochromatosis patients. When compared with the liver samples from normal controls, higher frequencies of G:C to T:A transversions at codon 249, and C:G to A:T transversions and C:G to T:A transitions at codon 250 were found in liver tissue from WND cases, and a higher frequency of G:C to T:A transversions at codon 249 was also found in liver tissue from hemochromatosis cases. Sixty percent of WND and 28% of hemochromatosis cases also showed a higher expression of inducible nitric oxide synthase in the liver, which suggested nitric oxide as a source of increased oxidative stress. The results were consistent with the hypothesis that the generation of oxygen/nitrogen species and unsaturated aldehydes from iron and copper overload in hemochromatosis and WND causes mutation in the p53 tumor suppressor gene. </p><p>Hedera et al. (2002) reported a 13-year-old male with Wilson disease who exhibited leukoencephalopathy early in the disease course. MRI showed increased signal intensities in the basal ganglia and throughout the subcortical white matter in the frontal lobes, which later extended to the parietal and occipital lobes. </p><p>Takeshita et al. (2002) investigated 2 families with Wilson disease in which sibs showed different clinical phenotypes and different ages at onset. In the first family, the second and fourth male children demonstrated onset of the neurologic type of Wilson disease at 16 and 28 years of age, respectively, and the first female child developed the hepatic type at 38 years of age. In family 2, the second male child showed neurologic symptoms at 32 years of age and was diagnosed as having the hepatoneurologic type of Wilson disease; the 35-year-old first female child was found to have the hepatic type in familial screening. In both families, affected individuals were compound heterozygotes for mutations in the ATP7B gene. In the first family, the mutations were R778L (606882.0009) and R919G (606882.0014). In the second family, the mutations were 2511delA (606882.0015) and A874V (606882.0016). </p><p>Hlubocka et al. (2002) studied 42 patients with Wilson disease (19 men and 23 women, mean age 34 +/- 10 years) and 42 age- and sex-matched healthy volunteers. All subjects underwent complete echocardiographic examination; 24-hour Holter monitoring was performed in 23 Wilson disease patients. In comparison with healthy subjects, patients with Wilson disease had increased thickness of the interventricular septum and left ventricular (LV) posterior wall. While the 2 groups did not differ in LV mass index, relative LV wall thickness was significantly increased in the Wilson disease patients compared to control subjects. Concentric LV remodeling was present in 9 patients (21%) and LV hypertrophy in 1 patient. Diastolic filling and the frequency of valvular abnormalities were comparable in both groups. Twenty-four-hour Holter monitoring detected ECG abnormalities in 10 patients (42%), the most frequent findings being runs of supraventricular tachycardias and frequent supraventricular ectopic beats. </p><p>Jung et al. (2005) reported a 17-year-old Korean man with Wilson disease who presented with polyneuropathy at least 6 months before developing more typical symptoms. Initial symptoms included intermittent paresthesia and weakness in both hands and feet with normal sensory examination. Nerve conduction studies and sural nerve biopsy were consistent with a mixed demyelinating and axonal neuropathy. Treatment with penicillamine, zinc sulfate, and vitamin B6 resulted in clinical improvement. </p>
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<strong>Diagnosis</strong>
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<p>Chowrimootoo et al. (1998) investigated the neonatal diagnosis of Wilson disease by measuring ceruloplasmin isoforms in neonatal cord blood samples and venous blood from both healthy adults and patients with Wilson disease. Total ceruloplasmin levels were reduced in all neonatal specimens. The plasma isoform, however, was significantly reduced or absent only in patients with Wilson disease, whereas the biliary isoform was reduced both in healthy neonates and patients with Wilson disease. The authors commented that measurement of ceruloplasmin isoforms in cord blood or dried blood spots may permit neonatal diagnosis of this condition, before substantial tissue damage has occurred. </p><p>Gow et al. (2000) reported their detailed experience of 30 patients with a diagnosis of Wilson disease seen in 2 Australian centers between 1971 and 1998. Twenty-two patients presented with chronic disease; age at diagnosis ranged from 7 to 58 years. Only 14 of these patients (64%) had Kayser-Fleischer rings; 5 of these had low serum ceruloplasmin concentrations and normal urinary copper excretion, 2 had normal ceruloplasmin levels and high urinary copper excretion, and 7 had the classic combination of low serum ceruloplasmin and high urinary copper. Eight patients presented with fulminant hepatic failure, with age at diagnosis ranging from 11 to 54 years; only 6 of these had Kayser-Fleischer rings, 7 had low serum ceruloplasmin, and 4 of them had raised urinary copper excretion. The others were anuric. Examination of the livers of these 8 patients, either at autopsy or posttransplantation, showed cirrhosis and elevated copper content. Gow et al. (2000) commented that the diagnosis of Wilson disease depended on the evaluation of clinical and laboratory evidence of abnormal copper metabolism, but that no single feature was reliable in isolation. Further, the authors suggested that Wilson disease should be considered in any patient at any age presenting with unusual liver or neurologic abnormalities. </p><p>Firneisz et al. (2001) described postmortem (postcremation) diagnosis of Wilson disease on the basis of skin cells left on the deceased's electric shaver. Foye (2001) and Kuruvilla (2001) took these authors to task, noting that the man's DNA added no new information since the same mutation was identified in the man's father and 2 children. Foye (2001) commented that with the growing array of available tests, 'we must always remember in each individual case to stop first and ask not just whether a particular test could be done, but whether it should be done.' Kuruvilla (2001) noted that the man had movement disorder for at least 10 years before his death and presented to his physician with parkinsonian symptoms and florid manifestations of cirrhosis. Because Kayser-Fleischer ring is present in 100% of patients with CNS manifestations of Wilson disease, neuroophthalmologic slit-lamp assessment is mandatory and cost effective in all patients suspected of having this disease. </p><p>Ferenci (2006) reviewed the geographic distribution of mutations in the ATP7B gene in Wilson disease patients to improve genetic diagnosis of Wilson disease. The most common mutation in patients from Europe is H1069Q (606882.0006). A unique 15-bp deletion in the 5-prime region (606882.0010) is frequent in Sardinia. M645R (606882.0020) is common in Spain, and R778L (606882.0009) is often found in patients from eastern Asia. Ferenci (2006) also presented a clinical algorithm for the diagnosis of Wilson disease. </p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
Cossu et al. (1992) demonstrated how one can use flanking markers to do prenatal diagnosis by the linkage principle in this disorder. The probability of the fetus being affected was estimated to be only 0.007 in the example given. </p>
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<strong>Clinical Management</strong>
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<p>Sokol et al. (1985) successfully treated a 13-year-old girl with fulminant Wilson disease with orthotopic liver transplant. Polson et al. (1987) reported dramatic improvement in neurologic function over a period of 3 or 4 months after orthotopic liver transplantation. However, Guarino et al. (1995) published a case of a man treated with orthotopic liver transplantation who developed postoperative central pontine and extrapontine myelinolysis and then went on to develop new extrapyramidal symptoms 19 months after the liver transplant. </p><p>Lingam et al. (1987) showed that neurologic abnormalities can be reversed to some extent in children with Wilson disease. In some patients it was necessary to substitute triethylene tetramine (TETA) for penicillamine because of adverse effects of the latter agent. Wilson disease is effectively treated by any 1 of 3 drugs, D-penicillamine, trien, or zinc acetate (Brewer et al., 1987). Brewer et al. (1994) described the successful treatment with zinc acetate of 13 presymptomatic patients identified through screening of sibs. The levels of hepatic copper in response to several years of zinc therapy may remain the same, go down, or go up temporarily. This is a reflection of zinc induction of hepatic metallothionein, which sequesters copper in a nontoxic pool. Hepatic copper levels should not be used to manage therapy. Liver function is well preserved by zinc therapy, and Brewer et al. (1994) observed no zinc toxicity in these 13 patients. Brewer et al. (1994) reported that no patient developed symptoms related to Wilson disease. However, Lang et al. (1993) reported a 30-year-old patient who deteriorated at the end of the first month of zinc therapy and died in hepatic coma. Hoogenraad (1994) expressed doubt that zinc played a causal role in the worsening condition of the patient reported by Lang et al. (1993). </p><p>Devesa et al. (1995) described an uneventful pregnancy with delivery of a healthy newborn in a woman with Wilson disease who had been on the oral copper-chelating agent trientine (triethylenetetramine dihydrochloride) because of the development of nephrosis when D-penicillamine was used. Hartard and Kunze (1994) reported a successful pregnancy in a patient with Wilson disease treated with D-penicillamine and zinc sulfate 3 years prior to and during the pregnancy. </p><p>Brewer et al. (1998) presented data on the long-term follow-up of maintenance zinc treatment of 141 symptomatic and presymptomatic patients with Wilson disease. From these data, they concluded that zinc is effective as a sole therapy and that it has low toxicity. The authors also presented limited data on zinc treatment of children and pregnant women with Wilson disease which were also suggestive of efficacy and low toxicity. </p><p>LeWitt (1999) observed that 'Whereas management of Wilson's disease follows some of the most logical treatment strategies in all of clinical neurology, the optimal means for removing copper from the brain (and elsewhere) have not achieved consensus.' Articles by Walshe (1999), who defended the use of penicillamine, and by Brewer (1999) indicated that the role of penicillamine, now in its fifth decade of use, is still a matter of great controversy. Brewer (1999) suggested that penicillamine should not be used as initial therapy in Wilson disease. He cited a number of instances of penicillamine-induced worsening. He favored the use of zinc acetate for maintenance therapy of Wilson disease and mentioned other alternative therapies. </p><p>By genetic analysis, Wu et al. (2003) identified 17 presymptomatic patients with Wilson disease. Prophylactic treatment of 14 patients with zinc over 3 to 5 years resulted in decreased levels of urinary copper, which indicated effective control of copper metabolism. None of the patients developed clinical symptoms of Wilson disease or adverse effects of zinc therapy by the end of the study period. In contrast, 3 patients who refused treatment had symptomatic progression of the disease. Wu et al. (2003) concluded that presymptomatic DNA diagnosis of individuals at risk and zinc therapy are effective treatment. </p><p>Treatment for patients with Wilson disease who present with neurologic manifestations is difficult because penicillamine often makes them neurologically worse and zinc is slow acting. Brewer et al. (2003) performed an open-label study of 55 untreated patients presenting with neurologic Wilson disease and treated them with tetrathiomolybdate varying from 120 to 410 mg/day for 8 weeks and then followed up for 3 years. Only 2 patients treated with tetrathiomolybdate (4%) showed neurologic deterioration, compared with an estimated 50% of penicillamine-treated patients. Five of the 22 new patients exhibited bone marrow suppression and 3 had aminotransferase elevations. These numbers were higher than in the original 33 patients and appeared to be due primarily to a more rapid dose escalation. Brewer et al. (2003) concluded that tetrathiomolybdate shows excellent efficacy in patients with Wilson disease who present with neurologic manifestations. With rapid escalation of dose, adverse effects from bone marrow suppression or aminotransferase elevations can occur. </p><p>In a randomized controlled double-blind study of 48 patients with neurologic presentation of Wilson disease, Brewer et al. (2006) concluded that tetrathiomolybdate was a better choice than trientine for preserving neurologic function. Six (26%) of 23 patients treated with trientine showed neurologic deterioration during the 8-week study compared to 1 (4%) of 25 patients treated with tetrathiomolybdate. </p><p>Alvarez et al. (2010) described how tetrathiomolybdate (TM) inhibits proteins that regulate copper physiology. Crystallographic results revealed that the surprising stability of the drug complex with the metallochaperone Atx1 (602270) arises from formation of a sulfur-bridged copper-molybdenum cluster reminiscent of those found in molybdenum and iron sulfur proteins. Spectroscopic studies indicated that this cluster is stable in solution and corresponds to physiologic clusters isolated from TM-treated Wilson disease animal models. Finally, mechanistic studies showed that the drug-metallochaperone inhibits metal transfer functions between copper-trafficking proteins. Alvarez et al. (2010) concluded that their results are consistent with a model wherein TM can directly and reversibly downregulate copper delivery to secreted metalloenzymes. </p>
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<strong>Mapping</strong>
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<span class="mim-text-font">
<p>In a large inbred kindred with affected persons in 2 generations, Frydman et al. (1985) investigated linkage of WND with 27 autosomal markers. A lod score of 3.21 was found at theta = 0.06 for linkage of WND and esterase D (ESD; 133280) on chromosome 13. In a note added in proof, they indicated that they had typed a second unrelated 10-member sibship with WND; the maximum lod score was 1.48 at theta = 0, giving a combined maximum lod score of 4.55 at theta = 0.04. Bonne-Tamir et al. (1985, 1986) corroborated the linkage of WND and esterase D by studies of another inbred group, 2 unrelated Druze kindreds. The combined lod score was 5.49 at theta = 0.03. Bonne-Tamir et al. (1986) confirmed the localization of Wilson disease by demonstration of linkage to DNA markers on chromosome 13; their studies indicated that the WND locus is distal to the ESD locus. Yuzbasiyan-Gurkan et al. (1988) confirmed the linkage to markers on chromosome 13, with a maximum lod score of 2.189 at theta = 0.06 for linkage of Wilson disease to D13S1. One very informative pedigree was Hispanic. One pedigree in which affected persons had normal or low normal levels of serum ceruloplasmin (a finding in only about 15% of WND patients) showed a negative lod score. The proband was not on oral contraceptives, and there was no known ceruloplasmin-inducing factor present. The family was of Russian-Jewish background. By genetic linkage studies, Bowcock et al. (1988) narrowed the assignment of the WND locus to 13q14-q21. Farrer et al. (1988) explored the use of linked genetic markers to identify carriers, normals, and presymptomatic affected persons. A significant decrease on the average was found in serum copper concentrations in heterozygotes, but other sources of variation in serum copper concentration were much greater and precluded use of serum copper for carrier detection. A familial component, independent of WND genotype, appeared to be a major factor accounting for variation in ceruloplasmin levels among unaffected persons. Figus et al. (1989) found no recombination with ESD and found linkage to several RFLPs. With ESD and 1 closely linked RFLP, they could either define the carrier status or exclude homozygosity in most unaffected sibs. The linkage of the WND locus to ESD at 13q14 was first shown by studies using the isozymic polymorphism of esterase D in families of Middle Eastern origin. Using RFLPs detected by the ESD cDNA, Houwen et al. (1990) could not confirm this reported close linkage in an analysis of 17 families of northwestern European origin. However, no crossovers were detected in 63 meioses informative for linkage with marker D13S12, located more distally at 13q21. The data confirmed the assignment of WND to 13q14-q21. Its localization, however, seemed to be more distal to ESD than previously reported. In a study of 20 families, Scheffer et al. (1992) found that D13S31 was the closest proximal marker and D13S55 and D13S26 the closest distal markers. They identified a crossover between WND and D13S31 in 1 family and a crossover between WND and D13S55 in another. These crossover sites could be used as reference points for new chromosome 13q14-q21 markers for a more accurate mapping of the WND locus. Using D13S31 and D13S59 (the closest proximal and distal markers, respectively, for the WND locus) in fluorescence in situ hybridization studies of chromosomal aberrations, Kooy et al. (1993) determined that the Wilson disease locus is located at the junction of bands q14.3 and q21.1. In 51 families with Wilson disease, Thomas et al. (1994) studied DNA haplotypes of CA dinucleotide repeat polymorphisms in the 13q14.3 region. They found that 3 markers (D13S314, D13S133, and D13S316) showed nonrandom distribution on chromosomes carrying the WND mutation. They also found that haplotypes of these 3 markers had highly significant differences between WND and normal haplotypes in northern European families. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The transmission pattern of Wilson disease in the patients reported by Bull et al. (1993) was consistent with autosomal recessive inheritance. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Bull et al. (1993) identified 2 patients with Wilson disease who were homozygous for a 7-bp deletion within the coding region of the ATP7B gene (606882.0001). Tanzi et al. (1993) identified 4 mutations in the ATP7B gene in unrelated persons with Wilson disease: 2 missense mutations (606882.0002-606882.0003) and 2 frameshift mutations resulting in a truncated gene product (606882.0004-606882.0005). The mutations were found among 50 unrelated families derived predominantly from the United States, 18 unrelated families from Russia, and 5 presumably unrelated families from Sicily. Clearly, Bull et al. (1993) and Tanzi et al. (1993) had independently isolated the same gene which was convincingly the one mutant in Wilson disease. </p><p>Thomas et al. (1995) reviewed the mutations found in the ATP7B gene. Their findings suggest a wide span in the age of onset of Wilson disease, perhaps wider than previously considered typical. Mutations that completely disrupt the gene can produce liver disease in early childhood at a time when Wilson disease may not be considered in the differential diagnosis. </p><p>Petrukhin et al. (1993) identified YACs spanning the Wilson disease region and derived cosmid contigs therefrom. Thirteen microsatellite markers were generated from cosmids and used for study of genetic equilibrium (linkage disequilibrium; LD). Strong LD was detected between these markers and the WND locus in 28 families from rural Russia, 43 families from Sardinia, and 67 families of predominantly North American and European descent. From their haplotype and mutation analyses, Petrukhin et al. (1993) predicted that approximately half of all Wilson disease mutations will be rare in the American and Russian populations. </p><p>Given the difficulties of searching for mutations in a gene spanning more than 80 kb of genomic DNA, haplotype data are important as a guide to mutation detection. Thomas et al. (1995) did haplotyping of the Wilson disease gene region in 58 families. These haplotypes, combining 3 markers (D13S314, D13S316, and D13S301), were usually specific for each different mutation. The haplotype data suggested that as many as 20 mutations might still be unidentified; a total of 25 disease-causing mutations had been identified at that time. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Gromadzka et al. (2005) studied 142 Polish patients with Wilson disease and identified 26 mutations in the ATP7B gene: 11 truncating, 14 missense, and 1 splice site mutation. Patients with 1 or 2 truncating mutations on their alleles had lower serum copper and ceruloplasmin levels and were younger when the first symptoms of the disease appeared compared with individuals with 2 missense mutations, and the effect of truncating mutations on phenotype was dose-dependent. Gromadzka et al. (2005) found no association between type of ATP7B mutation and mode of initial disease presentation (neurologic, hepatic, or mixed). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Figus et al. (1995) stated that the worldwide prevalence of Wilson disease is estimated to be on the order of 30 per 1 million, with a gene frequency of 0.56% and a carrier frequency of 1 in 90. They noted that a higher prevalence seems to exist in Sardinia, where approximately 10-12 new cases per year are identified. Figus et al. (1995) analyzed mutations and defined the chromosomal haplotype in 127 patients of Mediterranean descent affected by Wilson disease: 39 Sardinians, 49 Italians, 33 Turks, and 6 Albanians. There were 5 common haplotypes in Sardinians, 3 in Italians, and 2 in Turks, which accounted for 85%, 32%, and 30% of the Wilson disease chromosomes, respectively. They identified 16 novel mutations: 8 frameshifts, 7 missense mutations, and 1 splicing defect. In addition, they detected 5 previously described mutations, e.g., his1070-to-gln (606882.0006), which accounted for 13% of the mutations in WND chromosomes in non-Sardinian Mediterranean populations. </p><p>In the Sardinian population, one haplotype accounts for 55% of WND chromosomes (Figus et al., 1995). Loudianos et al. (1999) characterized the putative promoter and 5-prime untranslated region of the WND gene and carried out mutation analysis in this region in Sardinian patients with WND with the most common haplotype. They detected a single mutation resulting from a 15-nucleotide deletion (606882.0010) in all chromosomes with this common haplotype. With the addition of this mutation, the molecular defect has been found in 92% of the WD chromosomes in Sardinians. </p><p>Loudianos et al. (1998) performed a mutation screen on the WND gene in 59 patients of Mediterranean origin: 26 Continental Italians, 22 Sardinians, 9 Turkish, and 2 Albanians. They found 31 novel and 3 known mutations. Most of the patients were compound heterozygotes. Because there are so many causative mutations, the preclinical and prenatal diagnosis of Wilson disease should be carried out by a combination of mutation and linkage analysis. </p><p>Ha-Hao et al. (1998) performed mutation analysis in 33 German and 10 Cuban unrelated Wilson disease patients. The common his1069-to-gln (606882.0006) mutation accounted for 42% of all WND chromosomes in the German series and haplotype C was found to be highly predictive for this mutation. Six previously undescribed WND gene mutations were identified. In 15 German WND index patients and 3 sibs, both WND mutations could be determined and a genotype-phenotype correlation was attempted. Patients homozygous for the his1069-to-gln mutation showed almost a complete range of clinical presentations; thus, in this study, the his1069-to-gln mutation was not associated with a late neurologic presentation. </p><p>Kim et al. (1998) identified 3 novel mutations in the ATP7B gene in Korean patients with Wilson disease. One of these, arg778 to leu (R778L; 606882.0009), was found in 6 of 8 unrelated patients, giving an allele frequency of 37.5%. </p><p>In 120 unrelated Korean patients with Wilson disease, Park et al. (2007) identified 28 different mutations, including 6 novel mutations, in the ATP7B gene. They identified R778L as the most common mutation, occurring in 39.2% of mutant alleles. </p><p>In the Korean population, Park et al. (2009) found that the combined carrier frequency of 3 common ATP7B mutations, R778L, A874V (606882.0016), and N1270S (606882.0017), was 1 in 50 (2%). Extrapolating from this figure, the authors estimated that the carrier frequency of Wilson disease is about 1 in 27 in the Korean population, suggesting that the disorder is more common than in U.S. Caucasian populations. </p><p>Okada et al. (2000) analyzed the ATP7B gene in 41 unrelated Japanese Wilson disease families, including 47 patients. They identified 21 mutations, 9 of which were novel. </p><p>Garcia-Villarreal et al. (2000) identified a founder mutation in the ATP7B gene (L708P; 606882.0023) in 18 individuals with Wilson disease from the Canary Islands of Spain. Twelve patients were homozygous for the mutation. Homozygous patients tended to have a neurologic presentation at an average age of 16 years. The L708P mutation was estimated to have arisen in Gran Canaria over 56 generations ago, in pre-Hispanic times. Garcia-Villarreal et al. (2000) estimated a prevalence for Wilson disease of 1 in 2,600 individuals in the Canary Islands. </p><p>Margarit et al. (2005) analyzed 40 unrelated Spanish patients with Wilson disease and identified 21 different mutations in the ATP7B gene in 35 (87%) patients. The M645R (606882.0020) mutation was particularly prevalent and found in 22 patients (55%), who were all compound heterozygotes for mutation in the ATP7B gene. In 6 patients in whom M645R was combined with a nonsense mutation, there was early onset of the disease, occurring between 5 and 14 years of age. </p><p>Olivarez et al. (2001) undertook to estimate the frequency of Wilson disease in the U.S. Caucasian population. They used data from 4 studies to determine that approximately one-third of Wilson disease mutations in U.S. Caucasian Wilson disease patients are his1069-to-gln (H1069Q; 606882.0006). They then determined the frequency of this mutation in random DNA samples from 2,601 U.S. Caucasian newborns to be 0.285%. Multiplying by 3 gave an estimated Wilson disease heterozygote frequency of 0.855% and an allele frequency of 0.428%, or 0.00428. These data gave a Wilson disease frequency of about 1 in 55,000 births. The 95% confidence interval was rather broad, ranging from about 1 in 18,000 to 1 in 700,000 births. </p><p>Gupta et al. (2005) analyzed Indian patients with Wilson disease from 62 unrelated families and their first-degree relatives and identified a total of 9 mutations, 5 novel, in the ATP7B gene. The authors noted that homozygotes for different mutations that would be expected to produce similar defective proteins showed significant disparity in terms of organ involvement and severity of disease; in 1 family, 2 sibs with the same pair of mutant chromosomes had remarkably different phenotypes. Gupta et al. (2005) suggested that there may be as yet unidentified modifying loci that account for the observed phenotypic heterogeneity among patients with Wilson disease. </p><p>Mak et al. (2008) sequenced the ATP7B gene in 65 unrelated Han Chinese patients with Wilson disease and identified 126 disease alleles in 129 chromosomes (97.6% detection rate); the most prevalent mutation, R778L (606882.0009), was found in 22 chromosomes. The authors screened 660 healthy Hong Kong Han Chinese for R778L and a 2310C-G SNP in perfect linkage disequilibrium with R778L, and identified 3 carriers of both; neither variant was found in the remaining 657 individuals. Mak et al. (2008) calculated the prevalence of Wilson disease to be 1 in 5,400 in Hong Kong Han Chinese, and the East Asian-specific R778L mutation was estimated to have arisen 5,500 years earlier from a single ancestor. </p><p>Wang et al. (2011) identified 38 different pathogenic ATP7B mutations in 69 (69.86%) of 73 Chinese patients with Wilson disease. The most common mutation was R778L, which accounted for 23.29% mutant alleles, and the second most common mutation was I1148T (606882.0025), which accounted for 9.59% of mutant alleles. </p><p>Wallace and Dooley (2020) found that of the 732 Wilson disease-associated ATP7B mutations cataloged in the Wilson Disease Mutation Database (2010) and reported in the literature (2010-2017), 231 were present in the gnomAD database, resulting in an ATP7B pathogenic allele frequency of 2.055% and a heterozygous carrier rate of 1 in 25. The subpopulation in gnomAD with highest pathogenic allele frequency was the Ashkenazi Jewish population (3.005%), and the subpopulation with lowest pathogenic allele frequency was the African population (1.245%). Wallace and Dooley (2020) assessed the penetrance/pathogenicity of ATP7B mutations by comparing gnomAD allele frequencies with the number of reports of each mutation and then using a variant effect prediction algorithm. After excluding variants with predicted low penetrance, Wallace and Dooley (2020) calculated Wilson disease prevalence to be 1 in 20,000 individuals. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Li et al. (1991) found biochemical and morphologic evidence to suggest that the Long-Evans Cinnamon (LEC) rat is an authentic model of Wilson disease. Canine copper toxicosis, an autosomal recessive disorder, is thought to be an authentic model of Wilson disease. Yuzbasiyan-Gurkan et al. (1993) found, however, that in the dog the disorder is not linked (within 13% recombination) to the RB1 locus (614041) or (within 5% recombination) to the ESD locus (133280). Furthermore, ESD and RB1, tightly linked in both the mouse and human genomes, were not found to be closely linked in the canine genome. </p><p>In the LEC rat, acute hepatitis develops spontaneously about 4 months after birth, with clinical features similar to those seen in human fulminant hepatitis, sometimes a feature of Wilson disease. Survivors of this often-fatal attack continue to suffer from chronic hepatitis and usually develop hepatocellular carcinoma at age 12 months or older. Copper is abnormally high in the liver of LEC rats, and hepatitis can be prevented by treatment with copper-chelating agents such as D-penicillamine. Wu et al. (1994) cloned cDNAs for the rat gene (Atp7b; 606882) homologous to the human Wilson disease gene and used them to identify a partial deletion in the gene in the LEC rat. The deletion removed at least 900 basepairs of the coding region at the 3-prime end, including the crucial ATP-binding domain, and extended downstream of the gene. The usefulness of the model for studying liver pathophysiology, for developing therapy for Wilson disease, and for studying the pathway of copper transport and its possible interaction with other heavy metals was noted. </p><p>Theophilos et al. (1996) cloned and sequenced the murine homolog of the ATP7B gene. They demonstrated a point mutation in the 'toxic milk' (tx) mouse Atp7b gene. The coding sequence from the tx Atp7b gene was identical to the sequence from the DL mouse except for a single base change (A4066G) in the mutant sequence. Theophilos et al. (1996) reported that this base change led to a met1356-to-val amino acid substitution within the proposed eighth transmembrane domain of the Atp7b protein. Theophilos et al. (1996) reviewed the pathophysiology of the disorder in the tx mouse. They noted that tx is an autosomal recessive mutation which leads to hepatic accumulation of copper from the third postnatal week. The pups are born with an apparent copper deficiency and the milk of the mutant mothers is deficient in copper, leading to continued copper deficiency in the pups. The authors noted that the pathology observed in the livers of the deficient mice shows significant differences from the liver pathology observed in Wilson disease. Huang and Gitschier (1997) pointed out that tx, in which the milk of mutant dams is fatally deficient in copper, has a parallel in 'lethal milk' (lm) in which the milk of mutant dams is fatally deficient in zinc. Copper deficiency in human milk in Wilson disease has, it seems, not been investigated. The gene that is mutant in 'lethal milk' of the mouse is zinc transporter-4 (602095). </p><p>The mouse homologs for the Menkes (309400) and Wilson disease genes are the mottled (Atp7a; 300011) and toxic milk (Atp7b) genes, respectively. These genes encode similar copper-transporting P-type ATPases. They are expressed in different adult tissues in patterns reflecting disease manifestations. Using RNA in situ hybridization, Kuo et al. (1997) determined the distribution of mottled and toxic milk transcripts during mouse embryonic development. The mottled gene was expressed in all tissues throughout embryogenesis and was particularly strong in the choroid plexuses of the brain. Contrary to the previous observation of absent or very low expression in adult liver, mottled was expressed in embryonic liver. Expression of the toxic milk gene was significantly more delimited, with early expression in the central nervous system, heart, and liver. Later in gestation, toxic milk transcript was clearly seen in liver, intestine, thymus, and respiratory epithelium, including nasopharynx, trachea, and bronchi. In lung, toxic milk expression was restricted to bronchi, while mottled expression was diffuse. Hepatic expression of both toxic milk and mottled was in the parenchyma, as opposed to blood cells. These results suggested that the mottled gene product functions primarily in the homeostatic maintenance of cell copper levels, while the toxic milk gene product may be specifically involved in the biosynthesis of distinct cuproproteins in different tissues. </p><p>Using homologous recombination to disrupt the normal translation of the Atp7b gene, Buiakova et al. (1999) generated a strain of mice that were homozygous null mutants for the Wilson disease gene. The Atp7b-null mice displayed a gradual accumulation of hepatic copper that increased to a level 60-fold greater than normal by 5 months of age. An increase in copper concentration was also observed in the kidney, brain, placenta, and lactating mammary glands of homozygous mutants, although milk from the mutant glands was copper deficient. Morphologic abnormalities resembling cirrhosis developed in most animals older than 7 months of age. Progeny of the homozygous mutant females developed neurologic abnormalities and growth retardation characteristic of copper deficiency. Copper concentrations in the livers of the newborn homozygous null mutants were decreased dramatically. Thus, the authors concluded that inactivation of the murine Atp7b gene produces a form of cirrhotic liver disease that resembles Wilson disease in humans and the 'toxic milk' phenotype in mice. </p><p>Terada et al. (1998) introduced human ATP7B cDNA into the LEC rat using recombinant adenovirus-mediated gene delivery. An immunofluorescence study and a subcellular fractionation study revealed the transgene expression in liver and its localization to the Golgi apparatus. Moreover, since the synthesis of holoceruloplasmin is disturbed in the LEC rat, the plasma level of holoceruloplasmin, oxidase-active and copper-bound form, was examined to evaluate the function of ATP7B protein with respect to copper transport. Holoceruloplasmin was found in plasma of LEC rats who received ATP7B cDNA. Terada et al. (1998) concluded that introduced ATP7B protein may function in the copper transport coupled with the synthesis of ceruloplasmin and that the Golgi apparatus is the likely site for ATP7B protein to manifest its function. </p><p>By investigating the common autosomal recessive copper toxicosis in Bedlington terriers, van de Sluis et al. (1999) identified a new locus involved in progressive liver disease. Whereas the ATP7B gene mapped to canine chromosome 22q11, CO4107, a microsatellite marker showing close linkage to copper toxicosis, mapped to canine chromosome 10q26. A transcribed sequence identified from a CO4107-containing BAC was found to be homologous to a gene expressed from human chromosome 2p16-p13, a region devoid of any positional candidate genes. </p><p>In mouse hepatocytes, Lang et al. (2007) demonstrated that Cu(2+) induced the secretion of activated acid sphingomyelinase (SMPD1; 607608) from leukocytes, leading to ceramide release in and phosphatidylserine exposure on erythrocytes, which are events prevented by inhibition of Smpd1. In LEC rats, deficiency in or pharmacologic inhibition of Smpd1 prevented Cu(2+)-induced hepatocyte apoptosis and protected the rats from acute hepatocyte death, liver failure, and early death. Patients with Wilson disease showed elevated plasma levels of SMPD1 and displayed a constitutive increase of ceramide- and phosphatidylserine-positive erythrocytes. Lang et al. (2007) concluded that Cu(2+) triggers hepatocyte apoptosis through activation of acid sphingomyelinase and release of ceramide, suggesting a previously unidentified mechanism for liver cirrhosis and anemia in Wilson disease. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>A tribute to Dr. S. A. Kinnier Wilson and a comprehensive review of Wilson disease were published in 1988; see Marsden and Fahn (1988), Critchley (1988), Wilson (1988), and Walshe (1988). </p><p>Walshe (1996) provided a review of the historical background of the treatment of Wilson disease, beginning with BAL, which had practical problems, and continuing with the chelating agent EDTA, which proved disappointing, and ending up with penicillamine (Walshe, 1956). Almost overnight, Wilson disease became one of the few inherited metabolic disorders for which there was effective therapy. So successful did this prove that the fact that zinc salts could block copper from the gut and could be of therapeutic value passed virtually unnoticed. Hoogenraad and van den Hamer (1983) described its use. The third 'decoppering agent,' developed in the 1970s, was triethylene tetramine, as the dihydrochloride (Trientine). Walshe (1996) stated that a major and perhaps unexpected problem when initiating treatment is giving a 'reasonably accurate prognosis.' This may be related to the large number of different mutations and possible compound heterozygotes resulting in the varying clinical syndrome and different responses to treatment. He raised the question that initial deterioration seen in some patients after starting treatment may be due to free radical release in excess of the body's ability to remove them. He stated that the simultaneous administration of a free radical scavenger, such as alpha-tocopherol, might help eliminate the problem. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Anderson and Popper (1960); Bearn (1972); Carpenter et al. (1983);
Cartwright (1978); Czlonkowska and Rodo (1981); Dobyns et al. (1979);
Factor et al. (1982); Forbes and Cox (2000); Frommer et al. (1977);
Gadoth and Liel (1980); Gibbs and Walshe (1979); Goldstein et al.
(1971); Holtzman et al. (1967); Levi et al. (1967); McAlpine (1993);
Owen and Ludwig (1982); Saito (1983); Saito (1985); Sasaki et al.
(1994); Slovis et al. (1971); Sternlieb and Scheinberg (1972);
Strickland et al. (1973); Thomas et al. (1995); Walshe and Cumings
(1961); Wilson (1912)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Alvarez, H. M., Xue, Y., Robinson, C. D., Canalizo-Hernandez, M. A., Marvin, R. G., Kelly, R. A., Mondragon, A., Penner-Hahn, J. E., O'Halloran, T. V.
<strong>Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation.</strong>
Science 327: 331-334, 2010.
[PubMed: 19965379]
[Full Text: https://doi.org/10.1126/science.1179907]
</p>
</li>
<li>
<p class="mim-text-font">
Anderson, P. J., Popper, H.
<strong>Changes in hepatic structure in Wilson&#x27;s disease.</strong>
Am. J. Path. 36: 483-497, 1960.
[PubMed: 13793439]
</p>
</li>
<li>
<p class="mim-text-font">
Azizi, E., Eshel, G., Aladjem, M.
<strong>Hypercalciuria and nephrolithiasis as a presenting sign in Wilson disease.</strong>
Europ. J. Pediat. 148: 548-549, 1989.
[PubMed: 2744017]
[Full Text: https://doi.org/10.1007/BF00441555]
</p>
</li>
<li>
<p class="mim-text-font">
Bearn, A. G., McKusick, V. A.
<strong>Azure lunulae: an unusual change in the fingernails in two patients with hepatolenticular degeneration (Wilson&#x27;s disease).</strong>
J. Am. Med. Assoc. 166: 904-906, 1958.
[PubMed: 13502081]
[Full Text: https://doi.org/10.1001/jama.1958.62990080001010]
</p>
</li>
<li>
<p class="mim-text-font">
Bearn, A. G.
<strong>A genetical analysis of thirty families with Wilson&#x27;s disease (hepatolenticular degeneration).</strong>
Ann. Hum. Genet. 24: 33-43, 1960.
[PubMed: 13797909]
[Full Text: https://doi.org/10.1111/j.1469-1809.1959.tb01713.x]
</p>
</li>
<li>
<p class="mim-text-font">
Bearn, A. G.
<strong>Wilson&#x27;s disease.In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S. (eds.) : The Metabolic Basis of Inherited Disease. (3rd ed.)</strong>
New York: McGraw-Hill (pub.) 1972. Pp. 1033-1050.
</p>
</li>
<li>
<p class="mim-text-font">
Bonne-Tamir, B., Farrer, L. A., Frydman, M., Kanaaneh, H.
<strong>Evidence for linkage between Wilson disease and esterase D in three kindreds: detection of linkage for an autosomal recessive disorder by the family study method.</strong>
Genet. Epidemiol. 3: 201-209, 1986.
[PubMed: 3459695]
[Full Text: https://doi.org/10.1002/gepi.1370030307]
</p>
</li>
<li>
<p class="mim-text-font">
Bonne-Tamir, B., Farrer, L. A., Frydman, M., Kanani, C.
<strong>The locus for Wilson disease linked to esterase D in two Druze kindreds. (Abstract)</strong>
Am. J. Hum. Genet. 37: A47, 1985.
</p>
</li>
<li>
<p class="mim-text-font">
Bonne-Tamir, B., Frydman, M., Agger, M. S., Bekeer, R., Bowcock, A. M., Hebert, J. M., Cavalli-Sforza, L. L., Farrer, L. A.
<strong>Wilson&#x27;s disease in Israel: a genetic and epidemiological study.</strong>
Ann. Hum. Genet. 54: 155-168, 1990.
[PubMed: 2382969]
[Full Text: https://doi.org/10.1111/j.1469-1809.1990.tb00372.x]
</p>
</li>
<li>
<p class="mim-text-font">
Bowcock, A. M., Farrer, L. A., Hebert, J. M., Agger, M., Sternlieb, I., Scheinberg, I. H., Buys, C. H. C. M., Scheffer, H., Frydman, M., Chajek-Saul, T., Bonne-Tamir, B., Cavalli-Sforza, L. L.
<strong>Eight closely linked loci place the Wilson disease locus within 13q14-q21.</strong>
Am. J. Hum. Genet. 43: 664-674, 1988.
[PubMed: 3189332]
</p>
</li>
<li>
<p class="mim-text-font">
Brewer, G. J., Askari, F., Lorincz, M. T., Carlson, M., Schilsky, M., Kluin, K. J., Hedera, P., Moretti, P., Fink, J. K., Tankanow, R., Dick, R. B., Sitterly, J.
<strong>Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease.</strong>
Arch. Neurol. 63: 521-527, 2006.
[PubMed: 16606763]
[Full Text: https://doi.org/10.1001/archneur.63.4.521]
</p>
</li>
<li>
<p class="mim-text-font">
Brewer, G. J., Dick, R. D., Johnson, V. D., Brunberg, J. A., Kluin, K. J., Fink, J. K.
<strong>Treatment of Wilson&#x27;s disease with zinc. XV. Long-term follow-up studies.</strong>
J. Lab. Clin. Med. 132: 264-278, 1998.
[PubMed: 9794697]
[Full Text: https://doi.org/10.1016/s0022-2143(98)90039-7]
</p>
</li>
<li>
<p class="mim-text-font">
Brewer, G. J., Dick, R. D., Yuzbasiyan-Gurkan, V., Johnson, V., Wang, Y.
<strong>Treatment of Wilson&#x27;s disease with zinc XIII: therapy with zinc in presymptomatic patients from the time of diagnosis.</strong>
J. Lab. Clin. Med. 123: 849-858, 1994.
[PubMed: 8201263]
</p>
</li>
<li>
<p class="mim-text-font">
Brewer, G. J., Hedera, P., Kluin, K. J., Carlson, M., Askari, F., Dick, R. B., Sitterly, J., Fink, J. K.
<strong>Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy.</strong>
Arch. Neurol. 60: 379-385, 2003.
[PubMed: 12633149]
[Full Text: https://doi.org/10.1001/archneur.60.3.379]
</p>
</li>
<li>
<p class="mim-text-font">
Brewer, G. J., Yuzbasiyan-Gurkan, V., Young, A. B.
<strong>The treatment of Wilson&#x27;s disease.</strong>
Semin. Neurol. 7: 209-220, 1987.
[PubMed: 3332455]
[Full Text: https://doi.org/10.1055/s-2008-1041420]
</p>
</li>
<li>
<p class="mim-text-font">
Brewer, G. J.
<strong>Penicillamine should not be used as initial therapy in Wilson&#x27;s disease.</strong>
Mov. Disord. 14: 551-554, 1999.
[PubMed: 10435490]
[Full Text: https://doi.org/10.1002/1531-8257(199907)14:4&lt;551::aid-mds1002&gt;3.0.co;2-s]
</p>
</li>
<li>
<p class="mim-text-font">
Buiakova, O. I., Xu, J., Lutsenko, S., Zeitlin, S., Das, K., Das, S., Ross, B. M., Mekios, C., Scheinberg, I. H., Gilliam, T. C.
<strong>Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation.</strong>
Hum. Molec. Genet. 8: 1665-1671, 1999.
[PubMed: 10441329]
[Full Text: https://doi.org/10.1093/hmg/8.9.1665]
</p>
</li>
<li>
<p class="mim-text-font">
Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., Cox, D. W.
<strong>The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.</strong>
Nature Genet. 5: 327-337, 1993. Note: Erratum: Nature Genet. 6: 214 only, 1994.
[PubMed: 8298639]
[Full Text: https://doi.org/10.1038/ng1293-327]
</p>
</li>
<li>
<p class="mim-text-font">
Carpenter, T. O., Carnes, D. L., Anast, C. S.
<strong>Hypoparathyroidism in Wilson&#x27;s disease.</strong>
New Eng. J. Med. 309: 873-877, 1983.
[PubMed: 6888480]
[Full Text: https://doi.org/10.1056/NEJM198310133091501]
</p>
</li>
<li>
<p class="mim-text-font">
Cartwright, G. E.
<strong>Diagnosis of treatable Wilson&#x27;s disease.</strong>
New Eng. J. Med. 298: 1347-1350, 1978.
[PubMed: 349384]
[Full Text: https://doi.org/10.1056/NEJM197806152982406]
</p>
</li>
<li>
<p class="mim-text-font">
Chowrimootoo, G. F. E., Scowcroft, H., Seymour, C. A.
<strong>Caeruloplasmin isoforms in Wilson&#x27;s disease in neonates.</strong>
Arch. Dis. Child. Fetal Neonatal Ed. 79: F198-F201, 1998.
[PubMed: 10194991]
[Full Text: https://doi.org/10.1136/fn.79.3.f198]
</p>
</li>
<li>
<p class="mim-text-font">
Cossu, P., Pirastu, M., Nucaro, A., Figus, A., Balestrieri, A., Borrone, C., Giacchino, R., Devoto, M., Monni, G., Cao, A.
<strong>Prenatal diagnosis of Wilson&#x27;s disease by analysis of DNA polymorphism. (Letter)</strong>
New Eng. J. Med. 327: 57, 1992.
[PubMed: 1350853]
[Full Text: https://doi.org/10.1056/NEJM199207023270116]
</p>
</li>
<li>
<p class="mim-text-font">
Cox, D. W., Fraser, F. C., Sass-Kortsak, A.
<strong>A genetic study of Wilson&#x27;s disease: evidence for heterogeneity.</strong>
Am. J. Hum. Genet. 24: 646-666, 1972.
[PubMed: 5082916]
</p>
</li>
<li>
<p class="mim-text-font">
Critchley, M.
<strong>Remembering Kinnier Wilson.</strong>
Movement Disorders 3: 2-6, 1988.
[PubMed: 3050469]
[Full Text: https://doi.org/10.1002/mds.870030102]
</p>
</li>
<li>
<p class="mim-text-font">
Czaja, M. J., Weiner, F. R., Schwarzenberg, S. J., Sternlieb, I., Scheinberg, I. H., Van Thiel, D. H., LaRusso, N. F., Giambrone, M.-A., Kirschner, R., Koschinsky, M. L., MacGillivray, R. T. A., Zern, M. A.
<strong>Molecular studies of ceruloplasmin deficiency in Wilson&#x27;s disease.</strong>
J. Clin. Invest. 80: 1200-1204, 1987.
[PubMed: 3654978]
[Full Text: https://doi.org/10.1172/JCI113180]
</p>
</li>
<li>
<p class="mim-text-font">
Czlonkowska, A., Rodo, M.
<strong>Late onset of Wilson&#x27;s disease: report of a family.</strong>
Arch. Neurol. 38: 729-730, 1981.
[PubMed: 7305707]
[Full Text: https://doi.org/10.1001/archneur.1981.00510110089019]
</p>
</li>
<li>
<p class="mim-text-font">
Danks, D. M., Metz, G., Sewell, R., Prewett, E. J.
<strong>Wilson&#x27;s disease in adults with cirrhosis but no neurological abnormalities.</strong>
Brit. Med. J. 301: 331-332, 1990.
[PubMed: 2393743]
[Full Text: https://doi.org/10.1136/bmj.301.6747.331]
</p>
</li>
<li>
<p class="mim-text-font">
De Bie, P., Muller, P., Wijmenga, C., Klomp, L. W. J.
<strong>Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes.</strong>
J. Med. Genet. 44: 673-688, 2007.
[PubMed: 17717039]
[Full Text: https://doi.org/10.1136/jmg.2007.052746]
</p>
</li>
<li>
<p class="mim-text-font">
Devesa, R., Alvarez, A., de las Heras, G., de Miguel, J. R.
<strong>Wilson&#x27;s disease treated with trientine during pregnancy.</strong>
J. Pediat. Gastroent. Nutr. 20: 102-103, 1995.
[PubMed: 7884606]
[Full Text: https://doi.org/10.1097/00005176-199501000-00018]
</p>
</li>
<li>
<p class="mim-text-font">
Dobyns, W. B., Goldstein, N. P., Gordon, H.
<strong>Clinical spectrum of Wilson&#x27;s disease (hepatolenticular degeneration).</strong>
Mayo Clin. Proc. 54: 35-42, 1979.
[PubMed: 759736]
</p>
</li>
<li>
<p class="mim-text-font">
Factor, S. M., Cho, S., Sternlieb, I., Scheinberg, I. H., Goldfischer, S.
<strong>The cardiomyopathy of Wilson&#x27;s disease: myocardial alterations in nine cases.</strong>
Virchows Arch. A Path. Anat. Histol. 397: 301-311, 1982.
[PubMed: 7157667]
[Full Text: https://doi.org/10.1007/BF00496571]
</p>
</li>
<li>
<p class="mim-text-font">
Farrer, L. A., Bonne-Tamir, B., Frydman, M., Magazanik, A., Kidd, K. K., Bowcock, A. M., Cavalli-Sforza, L. L.
<strong>Predicting genotypes at loci for autosomal recessive disorders using linked genetic markers: application to Wilson&#x27;s disease.</strong>
Hum. Genet. 79: 109-117, 1988.
[PubMed: 3164701]
[Full Text: https://doi.org/10.1007/BF00280547]
</p>
</li>
<li>
<p class="mim-text-font">
Ferenci, P.
<strong>Regional distribution of mutations in the ATP7B gene in patients with Wilson disease: impact on genetic testing.</strong>
Hum. Genet. 120: 151-159, 2006.
[PubMed: 16791614]
[Full Text: https://doi.org/10.1007/s00439-006-0202-5]
</p>
</li>
<li>
<p class="mim-text-font">
Ferlan-Marolt, V., Stepec, S.
<strong>Fulminant Wilsonian hepatitis unmasked by disease progression: report of a case and review of the literature.</strong>
Dig. Dis. Sci. 44: 1054-1058, 1999.
[PubMed: 10235618]
[Full Text: https://doi.org/10.1023/a:1026637403894]
</p>
</li>
<li>
<p class="mim-text-font">
Figus, A., Angius, A., Loudianos, G., Bertini, C., Dessi, V., Loi, A., Deiana, M., Lovicu, M., Olla, N., Sole, G., De Virgiliis, S., Lilliu, F., and 21 others.
<strong>Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.</strong>
Am. J. Hum. Genet. 57: 1318-1324, 1995.
[PubMed: 8533760]
</p>
</li>
<li>
<p class="mim-text-font">
Figus, A., Lampis, R., Devoto, M., Ristaldi, M. S., Ideo, A., De Virgiliis, S., Nurchi, A. M., Corrias, A., Corda, R., Lai, M. E., Tocco, A., Deplano, A., Solinas, A., Zancan, L., Lee, W.-H., Cao, A., Pirastu, M., Balestrieri, A.
<strong>Carrier detection and early diagnosis of Wilson&#x27;s disease by restriction fragment length polymorphism analysis.</strong>
J. Med. Genet. 26: 78-82, 1989.
[PubMed: 2563776]
[Full Text: https://doi.org/10.1136/jmg.26.2.78]
</p>
</li>
<li>
<p class="mim-text-font">
Firneisz, G., Woller, J., Ferenci, P., Szalay, F.
<strong>Postcremation diagnosis from an electric shaver.</strong>
Lancet 358: 34 only, 2001.
[PubMed: 11454376]
[Full Text: https://doi.org/10.1016/S0140-6736(00)05254-5]
</p>
</li>
<li>
<p class="mim-text-font">
Fitzgerald, M. A., Gross, J. B., Goldstein, N. P., Wahner, H. W., McCall, J. T.
<strong>Wilson&#x27;s disease (hepatolenticular degeneration) of late adult onset: report of a case.</strong>
Mayo Clin. Proc. 50: 438-442, 1975.
[PubMed: 1152537]
</p>
</li>
<li>
<p class="mim-text-font">
Forbes, J. R., Cox, D. W.
<strong>Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.</strong>
Hum. Molec. Genet. 9: 1927-1935, 2000.
[PubMed: 10942420]
[Full Text: https://doi.org/10.1093/hmg/9.13.1927]
</p>
</li>
<li>
<p class="mim-text-font">
Foye, P. M.
<strong>Postcremation diagnosis. (Letter)</strong>
Lancet 358: 1554 only, 2001.
[PubMed: 11705608]
[Full Text: https://doi.org/10.1016/S0140-6736(01)06609-0]
</p>
</li>
<li>
<p class="mim-text-font">
Frommer, D., Morris, J., Sherlock, S., Abrams, J., Newman, S.
<strong>Kayser-Fleischer-like rings in patients without Wilson&#x27;s disease.</strong>
Gastroenterology 72: 1331-1335, 1977.
[PubMed: 558126]
</p>
</li>
<li>
<p class="mim-text-font">
Frydman, M., Bonne-Tamir, B., Farrer, L. A., Conneally, P. M., Magazanik, A., Ashbel, S., Goldwitch, Z.
<strong>Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase D locus.</strong>
Proc. Nat. Acad. Sci. 82: 1819-1821, 1985.
[PubMed: 3856863]
[Full Text: https://doi.org/10.1073/pnas.82.6.1819]
</p>
</li>
<li>
<p class="mim-text-font">
Gadoth, N., Liel, Y.
<strong>Transient external ophthalmoplegia in Wilson&#x27;s disease.</strong>
Metab. Pediat. Ophthal. 4: 71-72, 1980.
[PubMed: 7442347]
</p>
</li>
<li>
<p class="mim-text-font">
Garcia-Villarreal, L., Daniels, S., Shaw, S. H., Cotton, D., Galvin, M., Geskes, J., Bauer, P., Sierra-Hernandez, A., Buckler, A., Tugores, A.
<strong>High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.</strong>
Hepatology 32: 1329-1336, 2000.
[PubMed: 11093740]
[Full Text: https://doi.org/10.1053/jhep.2000.20152]
</p>
</li>
<li>
<p class="mim-text-font">
Gibbs, K., Walshe, J. M.
<strong>A study of the ceruloplasmin concentrations found in 75 patients with Wilson&#x27;s disease, their kinships and various control groups.</strong>
Quart. J. Med. 48: 447-463, 1979.
[PubMed: 396544]
</p>
</li>
<li>
<p class="mim-text-font">
Goldstein, N. P., Tauxe, W. N., McCall, J. T., Randall, R. V., Gross, J. B.
<strong>Wilson&#x27;s disease (hepatolenticular degeneration): treatment with penicillamine and changes in hepatic trappings of radioactive copper.</strong>
Arch. Neurol. 24: 391-400, 1971.
[PubMed: 5554863]
[Full Text: https://doi.org/10.1001/archneur.1971.00480350025002]
</p>
</li>
<li>
<p class="mim-text-font">
Gow, P. J., Smallwood, R. A., Angus, P. W., Smith, A. L., Wall, A. J., Sewell, R. B.
<strong>Diagnosis of Wilson&#x27;s disease: an experience over three decades.</strong>
Gut 46: 415-419, 2000.
[PubMed: 10673307]
[Full Text: https://doi.org/10.1136/gut.46.3.415]
</p>
</li>
<li>
<p class="mim-text-font">
Gromadzka, G., Schmidt, H. H.-J., Genschel, J., Bochow, B., Rodo, M., Tarnacka, B., Litwin, T., Chabik, G., Czlonkowska, A.
<strong>Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson&#x27;s disease.</strong>
Clin. Genet. 68: 524-532, 2005.
[PubMed: 16283883]
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00528.x]
</p>
</li>
<li>
<p class="mim-text-font">
Gu, M., Cooper, J. M., Butler, P., Walker, A. P., Mistry, P. K., Dooley, J. S., Schapira, A. H. V.
<strong>Oxidative-phosphorylation defects in liver of patients with Wilson&#x27;s disease.</strong>
Lancet 356: 469-474, 2000.
[PubMed: 10981891]
[Full Text: https://doi.org/10.1016/s0140-6736(00)02556-3]
</p>
</li>
<li>
<p class="mim-text-font">
Guarino, M., Stracciari, A., D'Alessandro, R., Pazzaglia, P.
<strong>No neurological improvement after liver transplantation for Wilson&#x27;s disease.</strong>
Acta Neurol. Scand. 92: 405-408, 1995.
[PubMed: 8610495]
[Full Text: https://doi.org/10.1111/j.1600-0404.1995.tb00155.x]
</p>
</li>
<li>
<p class="mim-text-font">
Gupta, A., Aikath, D., Neogi, R., Datta, S., Basu, K., Maity, B., Trivedi, R., Ray, J., Das, S. K., Gangopadhyay, P. K., Ray, K.
<strong>Molecular pathogenesis of Wilson disease: haplotype analysis, detection of prevalent mutations and genotype-phenotype correlation in Indian patients.</strong>
Hum. Genet. 118: 49-57, 2005.
[PubMed: 16133174]
[Full Text: https://doi.org/10.1007/s00439-005-0007-y]
</p>
</li>
<li>
<p class="mim-text-font">
Ha-Hao, D., Hefter, H., Stremmel, W., Castaneda-Guillot, C., Hernandez, A. H., Cox, D. W., Auburger, G.
<strong>His1069-to-gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.</strong>
Europ. J. Hum. Genet. 6: 616-623, 1998.
[PubMed: 9887381]
[Full Text: https://doi.org/10.1038/sj.ejhg.5200237]
</p>
</li>
<li>
<p class="mim-text-font">
Hartard, C., Kunze, K.
<strong>Pregnancy in a patient with Wilson&#x27;s disease treated with D-penicillamine and zinc sulfate: a case report and review of the literature.</strong>
Europ. Neurol. 34: 337-340, 1994.
[PubMed: 7851456]
[Full Text: https://doi.org/10.1159/000117074]
</p>
</li>
<li>
<p class="mim-text-font">
Hedera, P., Brewer, G. J., Fink, J. K.
<strong>White matter changes in Wilson disease. (Letter)</strong>
Arch. Neurol. 59: 866-867, 2002.
[PubMed: 12020274]
[Full Text: https://doi.org/10.1001/archneur.59.5.866]
</p>
</li>
<li>
<p class="mim-text-font">
Hlubocka, Z., Marecek, Z., Linhart, A., Kejrova, E., Pospisilova, L., Martasek, P., Aschermann, M.
<strong>Cardiac involvement in Wilson disease.</strong>
J. Inherit. Metab. Dis. 25: 269-277, 2002.
[PubMed: 12227457]
[Full Text: https://doi.org/10.1023/a:1016546223327]
</p>
</li>
<li>
<p class="mim-text-font">
Holtzman, N. A., Naughton, M. A., Iber, F. L., Gaumnitz, B. M.
<strong>Ceruloplasmin in Wilson&#x27;s disease.</strong>
J. Clin. Invest. 46: 993-1002, 1967.
[PubMed: 6026104]
[Full Text: https://doi.org/10.1172/JCI105606]
</p>
</li>
<li>
<p class="mim-text-font">
Hoogenraad, T. U., van den Hamer, C. J. A.
<strong>3 years of continuous oral zinc therapy in 4 patients with Wilson&#x27;s disease.</strong>
Acta Neurol. Scand. 67: 356-364, 1983.
[PubMed: 6613522]
[Full Text: https://doi.org/10.1111/j.1600-0404.1983.tb03153.x]
</p>
</li>
<li>
<p class="mim-text-font">
Hoogenraad, T. U.
<strong>Dangers of interrupting decoppering treatment in Wilson&#x27;s disease. (Letter)</strong>
Arch. Neurol. 51: 972-973, 1994.
[PubMed: 7945006]
[Full Text: https://doi.org/10.1001/archneur.1994.00540220018005]
</p>
</li>
<li>
<p class="mim-text-font">
Hoppe, B., Neuhaus, T., Superti-Furga, A., Forster, I., Leumann, E.
<strong>Hypercalciuria and nephrocalcinosis, a feature of Wilson&#x27;s disease.</strong>
Nephron 65: 460-462, 1993.
[PubMed: 8290000]
[Full Text: https://doi.org/10.1159/000187530]
</p>
</li>
<li>
<p class="mim-text-font">
Houwen, R. H. J., Scheffer, H., te Meerman, G. J., van der Vlies, P., Buys, C. H. C. M.
<strong>Close linkage of the Wilson&#x27;s disease locus to D13S12 in the chromosomal region 13q21 and not to ESD in 13q14.</strong>
Hum. Genet. 85: 560-562, 1990.
[PubMed: 2227943]
[Full Text: https://doi.org/10.1007/BF00194238]
</p>
</li>
<li>
<p class="mim-text-font">
Huang, L., Gitschier, J.
<strong>A novel gene involved in zinc transport is deficient in the lethal milk mouse.</strong>
Nature Genet. 17: 292-297, 1997.
[PubMed: 9354792]
[Full Text: https://doi.org/10.1038/ng1197-292]
</p>
</li>
<li>
<p class="mim-text-font">
Hussain, S. P., Raja, K., Amstad, P. A., Sawyer, M., Trudel, L. J., Wogan, G. N., Hofseth, L. J., Shields, P. G., Billiar, T. R., Trautwein, C., Hohler, T., Galle, P. R., Phillips, D. H., Markin, R., Marrogi, A. J., Harris, C. C.
<strong>Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: oxyradical overload diseases.</strong>
Proc. Nat. Acad. Sci. 97: 12770-12775, 2000.
[PubMed: 11050162]
[Full Text: https://doi.org/10.1073/pnas.220416097]
</p>
</li>
<li>
<p class="mim-text-font">
Jung, K.-H., Ahn, T.-B., Jeon, B. S.
<strong>Wilson disease with an initial manifestation of polyneuropathy.</strong>
Arch. Neurol. 62: 1628-1631, 2005.
[PubMed: 16216950]
[Full Text: https://doi.org/10.1001/archneur.62.10.1628]
</p>
</li>
<li>
<p class="mim-text-font">
Kim, E. K., Yoo, O. J., Song, K. Y., Yoo, H. W., Choi, S. Y., Cho, S. W., Hahn, S. H.
<strong>Identification of three novel mutations and a high frequency of the arg778-to-leu mutation in Korean patients with Wilson disease.</strong>
Hum. Mutat. 11: 275-278, 1998.
[PubMed: 9554743]
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:4&lt;275::AID-HUMU4&gt;3.0.CO;2-L]
</p>
</li>
<li>
<p class="mim-text-font">
Kooy, R. F., Van der Veen, A. Y., Verlind, E., Houwen, R. H. J., Scheffer, H., Buys, C. H. C. M.
<strong>Physical localisation of the chromosomal marker D13S31 places the Wilson disease locus at the junction of bands q14.3 and q21.1 of chromosome 13.</strong>
Hum. Genet. 91: 504-506, 1993.
[PubMed: 8314565]
[Full Text: https://doi.org/10.1007/BF00217780]
</p>
</li>
<li>
<p class="mim-text-font">
Kuan, P.
<strong>Cardiac Wilson&#x27;s disease.</strong>
Chest 91: 579-583, 1987.
[PubMed: 3829752]
[Full Text: https://doi.org/10.1378/chest.91.4.579]
</p>
</li>
<li>
<p class="mim-text-font">
Kuo, Y.-M., Gitschier, J., Packman, S.
<strong>Developmental expression of the mouse mottled and toxic milk genes suggests distinct functions for the Menkes and Wilson disease copper transporters.</strong>
Hum. Molec. Genet. 6: 1043-1049, 1997.
[PubMed: 9215673]
[Full Text: https://doi.org/10.1093/hmg/6.7.1043]
</p>
</li>
<li>
<p class="mim-text-font">
Kuruvilla, A.
<strong>Postcremation diagnosis. (Letter)</strong>
Lancet 358: 1554 only, 2001.
[PubMed: 11705607]
[Full Text: https://doi.org/10.1016/S0140-6736(01)06610-7]
</p>
</li>
<li>
<p class="mim-text-font">
Lang, C. J. G., Rabas-Kolominsky, P., Engelhardt, A., Kobras, G., Konig, H. J.
<strong>Fatal deterioration of Wilson&#x27;s disease after institution of oral zinc therapy. (Letter)</strong>
Arch. Neurol. 50: 1007-1008, 1993.
[PubMed: 8280286]
[Full Text: https://doi.org/10.1001/archneur.1993.00540100008005]
</p>
</li>
<li>
<p class="mim-text-font">
Lang, P. A., Schenck, M., Nicolay, J. P., Becker, J. U., Kempe, D. S., Lupescu, A., Koka, S., Eisele, K., Klarl, B. A., Rubben, H., Schmid, K. W., Mann, K., Hildenbrand, S., Hefter, H., Huber, S. M., Wieder, T., Erhardt, A., Haussinger, D., Gulbins, E., Lang, F.
<strong>Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide.</strong>
Nature Med. 13: 164-170, 2007.
[PubMed: 17259995]
[Full Text: https://doi.org/10.1038/nm1539]
</p>
</li>
<li>
<p class="mim-text-font">
Levi, A. J., Sherlock, S., Scheuer, P. J., Cumings, J. N.
<strong>Presymptomatic Wilson&#x27;s disease.</strong>
Lancet 290: 575-579, 1967. Note: Originally Volume II.
[PubMed: 4166824]
[Full Text: https://doi.org/10.1016/s0140-6736(67)90735-0]
</p>
</li>
<li>
<p class="mim-text-font">
LeWitt, P. A.
<strong>Penicillamine as a controversial treatment for Wilson&#x27;s disease. (Editorial)</strong>
Mov. Disord. 14: 555-556, 1999.
[PubMed: 10435491]
[Full Text: https://doi.org/10.1002/1531-8257(199907)14:4&lt;555::aid-mds1003&gt;3.0.co;2-l]
</p>
</li>
<li>
<p class="mim-text-font">
Li, Y., Togashi, Y., Sato, S., Emoto, T., Kang, J.-H., Takeichi, N., Kobayashi, H., Kojima, Y., Une, Y., Uchino, J.
<strong>Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis: a model of Wilson&#x27;s disease.</strong>
J. Clin. Invest. 87: 1858-1861, 1991.
[PubMed: 2022751]
[Full Text: https://doi.org/10.1172/JCI115208]
</p>
</li>
<li>
<p class="mim-text-font">
Lingam, S., Wilson, J., Nazer, H., Mowat, A. P.
<strong>Neurological abnormalities in Wilson&#x27;s disease are reversible.</strong>
Neuropediatrics 18: 11-12, 1987.
[PubMed: 3561699]
[Full Text: https://doi.org/10.1055/s-2008-1052427]
</p>
</li>
<li>
<p class="mim-text-font">
Litin, R. B., Randall, R. V., Goldstein, N. P., Power, M. H., Diessner, G. R.
<strong>Hypercalciuria in hepatolenticular degeneration (Wilson&#x27;s disease).</strong>
Am. J. Med. Sci. 238: 614-620, 1959.
[PubMed: 14417517]
</p>
</li>
<li>
<p class="mim-text-font">
Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Figus, A., Lilliu, F., De Virgiliis, S., Nurchi, A. M., Deplano, A., Moi, P., Pirastu, M., Cao, A.
<strong>Molecular characterization of Wilson disease in the Sardinian population--evidence of a founder effect.</strong>
Hum. Mutat. 14: 294-303, 1999.
[PubMed: 10502776]
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(199910)14:4&lt;294::AID-HUMU4&gt;3.0.CO;2-9]
</p>
</li>
<li>
<p class="mim-text-font">
Loudianos, G., Dessi, V., Lovicu, M., Angius, A., Nurchi, A., Sturniolo, G. C., Marcellini, M., Zancan, L., Bragetti, P., Akar, N., Yagci, R., Vegnente, A., Cao, A., Pirastu, M.
<strong>Further delineation of the molecular pathology of Wilson disease in the Mediterranean population.</strong>
Hum. Mutat. 12: 89-94, 1998.
[PubMed: 9671269]
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)12:2&lt;89::AID-HUMU3&gt;3.0.CO;2-G]
</p>
</li>
<li>
<p class="mim-text-font">
Mak, C. M., Lam, C.-W., Tam, S., Lai, C.-L., Chan, L.-Y., Fan, S.-T., Lau, Y.-L., Lai, S.-T., Yuen, P., Hui, J., Fu, C.-C., Wong, K.-S., and 13 others.
<strong>Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: identification of 17 novel mutations and its genetic heterogeneity.</strong>
J. Hum. Genet. 53: 55-63, 2008. Note: Erratum: J. Hum. Genet. 53: 375 only, 2008.
[PubMed: 18034201]
[Full Text: https://doi.org/10.1007/s10038-007-0218-2]
</p>
</li>
<li>
<p class="mim-text-font">
Margarit, E., Bach, V., Gomez, D., Bruguera, M., Jara, P., Queralt, R., Ballesta, F.
<strong>Mutation analysis of Wilson disease in the Spanish population--identification of a prevalent substitution and eight novel mutations in the ATP7B gene.</strong>
Clin. Genet. 68: 61-68, 2005.
[PubMed: 15952988]
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00439.x]
</p>
</li>
<li>
<p class="mim-text-font">
Marsden, C. D., Fahn, S.
<strong>Dr. S. A. Kinnier Wilson (1878-1937). (Editorial)</strong>
Mov. Disord. 3: 1 only, 1988.
</p>
</li>
<li>
<p class="mim-text-font">
McAlpine, P.
<strong>Personal Communication.</strong>
Winnipeg, Manitoba, Canada 11/12/1993.
</p>
</li>
<li>
<p class="mim-text-font">
Menerey, K. A., Eider, W., Brewer, G. J., Braunstein, E. M., Schumacher, H. R., Fox, I. H.
<strong>The arthropathy of Wilson&#x27;s disease: clinical and pathologic features.</strong>
J. Rheum. 15: 331-337, 1988.
[PubMed: 3361541]
</p>
</li>
<li>
<p class="mim-text-font">
Okada, T., Shiono, Y., Hayashi, H., Satoh, H., Sawada, T., Suzuki, A., Takeda, Y., Yano, M., Michitaka, K., Onji, M., Mabuchi, H.
<strong>Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson&#x27;s disease.</strong>
Hum. Mutat. 15: 454-462, 2000.
[PubMed: 10790207]
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(200005)15:5&lt;454::AID-HUMU7&gt;3.0.CO;2-J]
</p>
</li>
<li>
<p class="mim-text-font">
Olivarez, L., Caggana, M., Pass, K. A., Ferguson, P., Brewer, G. J.
<strong>Estimate of the frequency of Wilson&#x27;s disease in the US Caucasian population: a mutation analysis approach.</strong>
Ann. Hum. Genet. 65: 459-463, 2001.
[PubMed: 11806854]
[Full Text: https://doi.org/10.1017/S0003480001008764]
</p>
</li>
<li>
<p class="mim-text-font">
Owen, C. A., Jr., Ludwig, J.
<strong>Inherited copper toxicosis in Bedlington terriers: Wilson&#x27;s disease (hepatolenticular degeneration).</strong>
Am. J. Path. 106: 432-434, 1982.
[PubMed: 7065120]
</p>
</li>
<li>
<p class="mim-text-font">
Park, H.-D., Ki, C.-S., Lee, S.-Y., Kim, J.-W.
<strong>Carrier frequency of the R778L, A874V, and N1270S mutations in the ATP7B gene in a Korean population. (Letter)</strong>
Clin. Genet. 75: 405-407, 2009.
[PubMed: 19419418]
[Full Text: https://doi.org/10.1111/j.1399-0004.2008.01132.x]
</p>
</li>
<li>
<p class="mim-text-font">
Park, S., Park, J.-Y., Kim, G.-H., Choi, J.-H., Kim, K.-M., Kim, J.-B., Yoo, H.-W.
<strong>Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease.</strong>
Hum. Mutat. 28: 1108-1113, 2007.
[PubMed: 17587212]
[Full Text: https://doi.org/10.1002/humu.20574]
</p>
</li>
<li>
<p class="mim-text-font">
Passwell, J., Adam, A., Garfinkel, D., Streiffler, M., Cohen, B. E.
<strong>Heterogeneity of Wilson&#x27;s disease in Israel.</strong>
Isr. J. Med. Sci. 13: 15-19, 1977.
[PubMed: 838566]
</p>
</li>
<li>
<p class="mim-text-font">
Petrukhin, K., Fischer, S. G., Pirastu, M., Tanzi, R. E., Chernov, I., Devoto, M., Brzustowicz, L. M., Cayanis, E., Vitale, E., Russo, J. J., Matseoane, D., Boukhgalter, B., Wasco, W., Figus, A. L., Loudianos, J., Cao, A., Sternlieb, I., Evgrafov, O., Parano, E., Pavone, L., Warburton, D., Ott, J., Penchaszadeh, G. K., Scheinberg, I. H., Gilliam, T. C.
<strong>Mapping, cloning and genetic characterization of the region containing the Wilson disease gene.</strong>
Nature Genet. 5: 338-343, 1993.
[PubMed: 8298640]
[Full Text: https://doi.org/10.1038/ng1293-338]
</p>
</li>
<li>
<p class="mim-text-font">
Polson, R. J., Rolles, K., Calne, R. Y., Williams, R., Marsden, D.
<strong>Reversal of severe neurological manifestations of Wilson&#x27;s disease following orthotopic liver transplantation.</strong>
Quart. J. Med. 64: 685-691, 1987.
[PubMed: 3328213]
</p>
</li>
<li>
<p class="mim-text-font">
Ross, M. E., Jacobson, I. M., Dienstag, J. L., Martin, J. B.
<strong>Late-onset Wilson&#x27;s disease with neurological involvement in the absence of Kayser-Fleischer rings.</strong>
Ann. Neurol. 17: 411-413, 1985.
[PubMed: 4004163]
[Full Text: https://doi.org/10.1002/ana.410170421]
</p>
</li>
<li>
<p class="mim-text-font">
Saito, T.
<strong>Evaluation of segregation ratio in Wilson&#x27;s disease.</strong>
J. Med. Genet. 20: 271-275, 1983.
[PubMed: 6620327]
[Full Text: https://doi.org/10.1136/jmg.20.4.271]
</p>
</li>
<li>
<p class="mim-text-font">
Saito, T.
<strong>An expected decrease in incidence of Wilson&#x27;s disease due to decrease in consanguinity.</strong>
Jpn. J. Hum. Genet. 30: 249-253, 1985.
[PubMed: 3834206]
[Full Text: https://doi.org/10.1007/BF01876476]
</p>
</li>
<li>
<p class="mim-text-font">
Sasaki, N., Hayashizaki, Y., Muramatsu, M., Matsuda, Y., Ando, Y., Kuramoto, T., Serikawa, T., Azuma, T., Naito, A., Agui, T., Yamashita, T., Miyoshi, I., Takeichi, N., Kasai, N.
<strong>The gene responsible for LEC hepatitis, located on rat chromosome 16, is the homolog to the human Wilson disease gene.</strong>
Biochem. Biophys. Res. Commun. 202: 512-518, 1994.
[PubMed: 8037756]
[Full Text: https://doi.org/10.1006/bbrc.1994.1958]
</p>
</li>
<li>
<p class="mim-text-font">
Scheffer, H., Houwen, R. H. J., Te Meerman, G. J., Loessner, J., Bachmann, B., Kunert, E., Verlind, E., Buys, C. H. C. M.
<strong>Identification of crossovers in Wilson disease families as reference points for a genetic localization of the gene.</strong>
Hum. Genet. 89: 607-611, 1992.
[PubMed: 1511977]
[Full Text: https://doi.org/10.1007/BF00221947]
</p>
</li>
<li>
<p class="mim-text-font">
Shokeir, M. H. K., Shreffler, D. C.
<strong>Cytochrome oxidase deficiency in Wilson&#x27;s disease: a suggested ceruloplasmin function.</strong>
Proc. Nat. Acad. Sci. 62: 867-872, 1969.
[PubMed: 4308098]
[Full Text: https://doi.org/10.1073/pnas.62.3.867]
</p>
</li>
<li>
<p class="mim-text-font">
Shokeir, M. H. K.
<strong>Investigations on the nature of ceruloplasmin deficiency in the newborn.</strong>
Clin. Genet. 2: 223-227, 1971.
[PubMed: 5004412]
[Full Text: https://doi.org/10.1111/j.1399-0004.1971.tb00281.x]
</p>
</li>
<li>
<p class="mim-text-font">
Slovis, T. L., Dubois, R. S., Rodgerson, D. O., Silverman, A.
<strong>The varied manifestations of Wilson&#x27;s disease.</strong>
J. Pediat. 78: 578-584, 1971.
[PubMed: 5547815]
[Full Text: https://doi.org/10.1016/s0022-3476(71)80458-4]
</p>
</li>
<li>
<p class="mim-text-font">
Sokol, R. J., Francis, P. D., Gold, S. H., Ford, D. M., Lum, G. M., Ambruso, D. R.
<strong>Orthotopic liver transplantation for acute fulminant Wilson disease.</strong>
J. Pediat. 107: 549-552, 1985.
[PubMed: 3900322]
[Full Text: https://doi.org/10.1016/s0022-3476(85)80016-0]
</p>
</li>
<li>
<p class="mim-text-font">
Starosta-Rubinstein, S., Young, A. B., Kluin, K., Hill, G., Aisen, A. M., Gabrielsen, T., Brewer, G. J.
<strong>Clinical assessment of 31 patients with Wilson&#x27;s disease: correlations with structural changes on magnetic resonance imaging.</strong>
Arch. Neurol. 44: 365-370, 1987.
[PubMed: 3827691]
[Full Text: https://doi.org/10.1001/archneur.1987.00520160007005]
</p>
</li>
<li>
<p class="mim-text-font">
Sternlieb, I., Scheinberg, I. H.
<strong>Chronic hepatitis as a first manifestation of Wilson&#x27;s disease.</strong>
Ann. Intern. Med. 76: 59-64, 1972.
[PubMed: 5021554]
[Full Text: https://doi.org/10.7326/0003-4819-76-1-59]
</p>
</li>
<li>
<p class="mim-text-font">
Strickland, G. T., Frommer, D., Leu, M. L., Pollard, R., Sherlock, S., Cumings, J. N.
<strong>Wilson&#x27;s disease in the United Kingdom and Taiwan. I. General characteristics of 142 cases and prognosis. II. A genetic analysis of 88 cases.</strong>
Quart. J. Med. 42: 619-638, 1973.
[PubMed: 4199472]
</p>
</li>
<li>
<p class="mim-text-font">
Takeshita, Y., Shimizu, N., Yamaguchi, Y., Nakazono, H., Saitou, M., Fujikawa, Y., Aoki, T.
<strong>Two families with Wilson disease in which siblings showed different phenotypes.</strong>
J. Hum. Genet. 47: 543-547, 2002.
[PubMed: 12376745]
[Full Text: https://doi.org/10.1007/s100380200082]
</p>
</li>
<li>
<p class="mim-text-font">
Tanzi, R. E., Petrukhin, K., Chernov, I., Pellequer, J. L., Wasco, W., Ross, B., Romano, D. M., Parano, E., Pavone, L., Brzustowicz, L. M., Devoto, M., Peppercorn, J., Bush, A. I., Sternlieb, I., Pirastu, M., Gusella, J. F., Evgrafov, O., Penchaszadeh, G. K., Honig, B., Edelman, I. S., Soares, M. B., Scheinberg, I. H., Gilliam, T. C.
<strong>The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.</strong>
Nature Genet. 5: 344-350, 1993.
[PubMed: 8298641]
[Full Text: https://doi.org/10.1038/ng1293-344]
</p>
</li>
<li>
<p class="mim-text-font">
Terada, K., Nakako, T., Yang, X.-L., Iida, M., Aiba, N., Minamiya, Y., Nakai, M., Sakaki, T., Miura, N., Sugiyama, T.
<strong>Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.</strong>
J. Biol. Chem. 273: 1815-1820, 1998.
[PubMed: 9430732]
[Full Text: https://doi.org/10.1074/jbc.273.3.1815]
</p>
</li>
<li>
<p class="mim-text-font">
Theophilos, M. B., Cox, D. W., Mercer, J. F. B.
<strong>The toxic milk mouse is a murine model of Wilson disease.</strong>
Hum. Molec. Genet. 5: 1619-1624, 1996.
[PubMed: 8894697]
[Full Text: https://doi.org/10.1093/hmg/5.10.1619]
</p>
</li>
<li>
<p class="mim-text-font">
Thomas, G. R., Bull, P. C., Roberts, E. A., Walshe, J. M., Cox, D. W.
<strong>Haplotype studies in Wilson disease.</strong>
Am. J. Hum. Genet. 54: 71-78, 1994.
[PubMed: 8279472]
</p>
</li>
<li>
<p class="mim-text-font">
Thomas, G. R., Forbes, J. R., Roberts, E. A., Walshe, J. M., Cox, D. W.
<strong>The Wilson disease gene: spectrum of mutations and their consequences.</strong>
Nature Genet. 9: 210-217, 1995. Note: Erratum:. Nature Genet. 9: 451 only, 1995.
[PubMed: 7626145]
[Full Text: https://doi.org/10.1038/ng0295-210]
</p>
</li>
<li>
<p class="mim-text-font">
Thomas, G. R., Jensson, O., Gudmundsson, G., Thorsteinsson, L., Cox, D. W.
<strong>Wilson disease in Iceland: a clinical and genetic study.</strong>
Am. J. Hum. Genet. 56: 1140-1146, 1995.
[PubMed: 7726170]
</p>
</li>
<li>
<p class="mim-text-font">
Thomas, G. R., Roberts, E. A., Walshe, J. M., Cox, D. W.
<strong>Haplotypes and mutations in Wilson disease.</strong>
Am. J. Hum. Genet. 56: 1315-1319, 1995.
[PubMed: 7762553]
</p>
</li>
<li>
<p class="mim-text-font">
van de Sluis, B. J. A., Breen, M., Nanji, M., van Wolferen, M., de Jong, P., Binns, M. M., Pearson, P. L., Kuipers, J., Rothuizen, J., Cox, D. W., Wijmenga, C., van Oost, B. A.
<strong>Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13-p16.</strong>
Hum. Molec. Genet. 8: 501-507, 1999.
[PubMed: 9949209]
[Full Text: https://doi.org/10.1093/hmg/8.3.501]
</p>
</li>
<li>
<p class="mim-text-font">
van Wassenaer-van Hall, H. N., van den Heuvel, A. G., Jansen, G. H., Hoogenraad, T. U., Mali, W. P. T. M.
<strong>Cranial MR in Wilson disease: abnormal white matter in extrapyramidal and pyramidal tracts.</strong>
Am. J. Neuroradiol. 16: 2021-2027, 1995.
[PubMed: 8585490]
</p>
</li>
<li>
<p class="mim-text-font">
Wallace, D. F., Dooley, J. S.
<strong>ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease.</strong>
Hum. Genet. 139: 1065-1075, 2020.
[PubMed: 32248359]
[Full Text: https://doi.org/10.1007/s00439-020-02161-3]
</p>
</li>
<li>
<p class="mim-text-font">
Walshe, J. M., Cumings, J. N.
<strong>Wilson&#x27;s Disease: Some Current Concepts.</strong>
Oxford: Blackwell (pub.) 1961. Pp. 1-292.
</p>
</li>
<li>
<p class="mim-text-font">
Walshe, J. M.
<strong>Penicillamine, a new oral therapy for Wilson&#x27;s disease.</strong>
Am. J. Med. 21: 487-495, 1956.
[PubMed: 13362281]
[Full Text: https://doi.org/10.1016/0002-9343(56)90066-3]
</p>
</li>
<li>
<p class="mim-text-font">
Walshe, J. M.
<strong>Wilson&#x27;s disease: yesterday, today, and tomorrow.</strong>
Movement Disorders 3: 10-29, 1988.
[PubMed: 3050468]
[Full Text: https://doi.org/10.1002/mds.870030104]
</p>
</li>
<li>
<p class="mim-text-font">
Walshe, J. M.
<strong>Treatment of Wilson&#x27;s disease: the historical background.</strong>
Quart. J. Med. 89: 553-555, 1996.
[PubMed: 8759497]
[Full Text: https://doi.org/10.1093/qjmed/89.7.553]
</p>
</li>
<li>
<p class="mim-text-font">
Walshe, J. M.
<strong>Penicillamine: the treatment of first choice for patients with Wilson&#x27;s disease.</strong>
Mov. Disord. 14: 545-550, 1999.
[PubMed: 10435489]
[Full Text: https://doi.org/10.1002/1531-8257(199907)14:4&lt;545::aid-mds1001&gt;3.0.co;2-u]
</p>
</li>
<li>
<p class="mim-text-font">
Wang, L.-H., Huang, Y.-Q., Shang, X., Su, Q.-X., Xiong, F., Yu, Q.-Y., Lin, H.-P., Wei, Z.-S., Hong, M.-F., Xu, X.-M.
<strong>Mutation analysis of 73 southern Chinese Wilson&#x27;s disease patients: identification of 10 novel mutations and its clinical correlation.</strong>
J. Hum. Genet. 56: 660-665, 2011.
[PubMed: 21796144]
[Full Text: https://doi.org/10.1038/jhg.2011.76]
</p>
</li>
<li>
<p class="mim-text-font">
Whelton, M. J., Pope, F. M.
<strong>Azure lunules in argyria: corneal changes resembling Kayser-Fleischer rings.</strong>
Arch. Intern. Med. 121: 267-269, 1968.
[PubMed: 5642746]
</p>
</li>
<li>
<p class="mim-text-font">
Wiebers, D. O., Wilson, D. M., McLeod, R. A., Goldstein, N. P.
<strong>Renal stones in Wilson&#x27;s disease.</strong>
Am. J. Med. 67: 249-254, 1979.
[PubMed: 463930]
[Full Text: https://doi.org/10.1016/0002-9343(79)90399-1]
</p>
</li>
<li>
<p class="mim-text-font">
Wilson, J. V.
<strong>Memories of my father.</strong>
Movement Disorders 3: 7-9, 1988.
[PubMed: 3050473]
[Full Text: https://doi.org/10.1002/mds.870030103]
</p>
</li>
<li>
<p class="mim-text-font">
Wilson, S. A. K.
<strong>Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver.</strong>
Brain 34: 295-507, 1912.
</p>
</li>
<li>
<p class="mim-text-font">
Wu, J., Forbes, J. R., Chen, H. S., Cox, D. W.
<strong>The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene.</strong>
Nature Genet. 7: 541-545, 1994.
[PubMed: 7951327]
[Full Text: https://doi.org/10.1038/ng0894-541]
</p>
</li>
<li>
<p class="mim-text-font">
Wu, Z.-Y., Lin, M.-T., Murong, S.-X., Wang, N.
<strong>Molecular diagnosis and prophylactic therapy for presymptomatic Chinese patients with Wilson disease.</strong>
Arch. Neurol. 60: 737-741, 2003.
[PubMed: 12756138]
[Full Text: https://doi.org/10.1001/archneur.60.5.737]
</p>
</li>
<li>
<p class="mim-text-font">
Yuzbasiyan-Gurkan, V., Brewer, G. J., Boerwinkle, E., Venta, P. J.
<strong>Linkage of the Wilson disease gene to chromosome 13 in North-American pedigrees.</strong>
Am. J. Hum. Genet. 42: 825-829, 1988.
[PubMed: 3163469]
</p>
</li>
<li>
<p class="mim-text-font">
Yuzbasiyan-Gurkan, V., Wagnitz, S., Blanton, S. H., Brewer, G. J.
<strong>Linkage studies of the esterase D and retinoblastoma genes to canine copper toxicosis: a model for Wilson disease.</strong>
Genomics 15: 86-90, 1993.
[PubMed: 8432554]
[Full Text: https://doi.org/10.1006/geno.1993.1013]
</p>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
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Contributors:
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Hilary J. Vernon - updated : 02/03/2021<br>Cassandra L. Kniffin - updated : 11/1/2011<br>Cassandra L. Kniffin - updated : 12/22/2010<br>Ada Hamosh - updated : 2/1/2010<br>Marla J. F. O&#x27;Neill - updated : 11/18/2008<br>Cassandra L. Kniffin - updated : 1/2/2008<br>Cassandra L. Kniffin - updated : 11/14/2007<br>Marla J. F. O&#x27;Neill - updated : 4/12/2007<br>Cassandra L. Kniffin - updated : 3/21/2007<br>Cassandra L. Kniffin - updated : 2/6/2007<br>Cassandra L. Kniffin - updated : 11/2/2006<br>Marla J. F. O&#x27;Neill - updated : 10/25/2006<br>Cassandra L. Kniffin - updated : 6/9/2006<br>Marla J. F. O&#x27;Neill - updated : 12/28/2005<br>Marla J. F. O&#x27;Neill - updated : 7/5/2005<br>Ada Hamosh - updated : 10/8/2003<br>Ada Hamosh - updated : 7/8/2003<br>Cassandra L. Kniffin - updated : 6/2/2003<br>Victor A. McKusick - updated : 3/6/2003<br>Victor A. McKusick - updated : 1/7/2003<br>Cassandra L. Kniffin - updated : 12/9/2002<br>Cassandra L. Kniffin - reorganized : 4/29/2002<br>Cassandra L. Kniffin - updated : 4/29/2002<br>Deborah L. Stone - updated : 3/22/2002<br>Victor A. McKusick - updated : 3/7/2002<br>Victor A. McKusick - updated : 2/8/2002<br>George E. Tiller - updated : 4/24/2001<br>Victor A. McKusick - updated : 11/30/2000<br>George E. Tiller - updated : 10/25/2000<br>Ada Hamosh - updated : 10/4/2000<br>Ada Hamosh - updated : 9/13/2000<br>Victor A. McKusick - updated : 5/19/2000<br>Paul Brennan - updated : 5/3/2000<br>Victor A. McKusick - updated : 3/24/2000<br>Paul Brennan - updated : 2/21/2000<br>Victor A. McKusick - updated : 2/1/2000<br>Wilson H. Y. Lo - updated : 11/17/1999<br>Victor A. McKusick - updated : 10/13/1999<br>Sonja A. Rasmussen - updated : 6/30/1999<br>Victor A. McKusick - updated : 6/11/1999<br>Victor A. McKusick - updated : 4/7/1999<br>Victor A. McKusick - updated : 3/17/1999<br>Victor A. McKusick - updated : 9/18/1998<br>Victor A. McKusick - updated : 8/5/1998<br>Victor A. McKusick - updated : 4/29/1998<br>Victor A. McKusick - updated : 10/27/1997<br>Victor A. McKusick - updated : 8/15/1997<br>Moyra Smith - updated : 12/16/1996<br>Orest Hurko - updated : 3/6/1996<br>Alan F. Scott - updated : 9/27/1995<br>Orest Hurko - updated : 9/21/1995
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Victor A. McKusick : 6/4/1986
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alopez : 09/23/2024<br>carol : 01/31/2024<br>carol : 08/09/2022<br>alopez : 08/08/2022<br>carol : 02/04/2021<br>carol : 02/03/2021<br>carol : 03/25/2020<br>carol : 05/17/2019<br>alopez : 05/15/2019<br>carol : 12/06/2018<br>carol : 07/09/2016<br>carol : 5/8/2015<br>terry : 11/6/2012<br>terry : 9/14/2012<br>carol : 8/8/2012<br>carol : 11/1/2011<br>ckniffin : 11/1/2011<br>carol : 6/17/2011<br>terry : 4/25/2011<br>carol : 3/24/2011<br>carol : 3/22/2011<br>wwang : 12/29/2010<br>ckniffin : 12/22/2010<br>carol : 10/21/2010<br>terry : 10/14/2010<br>terry : 10/12/2010<br>alopez : 2/2/2010<br>terry : 2/1/2010<br>terry : 6/3/2009<br>terry : 3/26/2009<br>wwang : 11/25/2008<br>terry : 11/18/2008<br>wwang : 1/15/2008<br>ckniffin : 1/2/2008<br>wwang : 12/14/2007<br>ckniffin : 11/14/2007<br>wwang : 4/17/2007<br>terry : 4/12/2007<br>wwang : 4/4/2007<br>ckniffin : 3/21/2007<br>wwang : 2/7/2007<br>ckniffin : 2/6/2007<br>wwang : 11/7/2006<br>ckniffin : 11/2/2006<br>wwang : 10/26/2006<br>terry : 10/25/2006<br>wwang : 6/23/2006<br>ckniffin : 6/9/2006<br>wwang : 1/5/2006<br>terry : 12/28/2005<br>wwang : 7/11/2005<br>wwang : 7/11/2005<br>terry : 7/5/2005<br>terry : 4/4/2005<br>cwells : 10/8/2003<br>alopez : 7/9/2003<br>terry : 7/8/2003<br>ckniffin : 6/2/2003<br>carol : 3/10/2003<br>carol : 3/10/2003<br>tkritzer : 3/6/2003<br>tkritzer : 3/6/2003<br>cwells : 1/8/2003<br>tkritzer : 1/7/2003<br>carol : 12/16/2002<br>tkritzer : 12/12/2002<br>ckniffin : 12/9/2002<br>carol : 4/29/2002<br>carol : 4/29/2002<br>ckniffin : 4/29/2002<br>carol : 4/29/2002<br>ckniffin : 4/29/2002<br>carol : 4/8/2002<br>terry : 3/22/2002<br>cwells : 3/18/2002<br>cwells : 3/15/2002<br>terry : 3/7/2002<br>alopez : 2/18/2002<br>terry : 2/8/2002<br>cwells : 5/1/2001<br>cwells : 4/24/2001<br>mcapotos : 12/12/2000<br>mcapotos : 12/7/2000<br>terry : 11/30/2000<br>carol : 11/17/2000<br>carol : 11/1/2000<br>mcapotos : 10/25/2000<br>alopez : 10/4/2000<br>alopez : 10/3/2000<br>terry : 9/13/2000<br>mcapotos : 6/5/2000<br>mcapotos : 5/26/2000<br>terry : 5/19/2000<br>alopez : 5/8/2000<br>alopez : 5/3/2000<br>mcapotos : 4/18/2000<br>mcapotos : 4/14/2000<br>terry : 3/24/2000<br>alopez : 2/22/2000<br>alopez : 2/21/2000<br>alopez : 2/21/2000<br>mcapotos : 2/14/2000<br>mcapotos : 2/9/2000<br>terry : 2/1/2000<br>terry : 2/1/2000<br>carol : 11/17/1999<br>mgross : 10/18/1999<br>terry : 10/13/1999<br>carol : 6/30/1999<br>kayiaros : 6/30/1999<br>kayiaros : 6/29/1999<br>jlewis : 6/17/1999<br>terry : 6/11/1999<br>mgross : 4/7/1999<br>carol : 3/31/1999<br>terry : 3/17/1999<br>carol : 12/9/1998<br>carol : 11/3/1998<br>carol : 9/24/1998<br>terry : 9/18/1998<br>alopez : 8/7/1998<br>terry : 8/5/1998<br>carol : 5/8/1998<br>terry : 4/29/1998<br>mark : 10/28/1997<br>terry : 10/27/1997<br>mark : 9/1/1997<br>jenny : 8/19/1997<br>terry : 8/15/1997<br>terry : 7/9/1997<br>mark : 6/10/1997<br>terry : 2/3/1997<br>mark : 12/16/1996<br>jamie : 11/22/1996<br>terry : 11/14/1996<br>terry : 11/11/1996<br>terry : 4/15/1996<br>mark : 3/6/1996<br>terry : 2/29/1996<br>mark : 12/15/1995<br>terry : 12/13/1995<br>mark : 7/21/1995<br>davew : 8/31/1994<br>terry : 8/26/1994<br>mimadm : 4/29/1994
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