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Entry
- #128101 - DYSTONIA 4, TORSION, AUTOSOMAL DOMINANT; DYT4
- OMIM
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<span class="h4">#128101</span>
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/128101"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS128100"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#history">History</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">Clinical Resources</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
<div class="panel-body small mim-panel-body">
<div><a href="https://clinicaltrials.gov/search?cond=(DYSTONIA 4, TORSION, AUTOSOMAL DOMINANT) OR (TUBB4A)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=13822&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
<div><a href="https://www.diseaseinfosearch.org/x/2418" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=128101[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98805" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
</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="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<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:0090041" 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/128101" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0090041" 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>
</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>ORPHA:</strong> 98805<br />
<strong>DO:</strong> 0090041<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>
128101
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
DYSTONIA 4, TORSION, AUTOSOMAL DOMINANT; DYT4
</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">
WHISPERING DYSPHONIA, HEREDITARY<br />
DYSTONIA MUSCULORUM DEFORMANS 4
</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/19/185?start=-3&limit=10&highlight=185">
19p13.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Dystonia 4, torsion, autosomal dominant
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128101"> 128101 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
TUBB4A
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602662"> 602662 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/128101" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS128100" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
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</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/128101" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/128101" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thin body habitus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61294007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61294007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0039870&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039870</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001533" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001533</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001533" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001533</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thin face <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849121&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849121</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000275" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000275</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000275" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000275</a>]</span><br /> -
Hollowed cheeks <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4024154&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4024154</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009938" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009938</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Bradykinetic tongue <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805539&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805539</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Neck </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Torticollis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70070008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70070008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M43.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M43.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/723.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">723.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040485&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040485</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000473" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000473</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000473" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000473</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Larynx </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Laryngeal adductor spasmodic dysphonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805536&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805536</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> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- 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 />
</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">
- Torsion dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/431034009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">431034009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013423&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013423</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001304" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001304</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001304" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001304</a>]</span><br /> -
Dysphonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16617009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16617009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R49.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R49.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/784.42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.42</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1527344&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1527344</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001618</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001618</a>]</span><br /> -
Generalized dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/425492002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">425492002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848954&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848954</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007325" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007325</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007325" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007325</a>]</span><br /> -
Limb dystonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751093&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751093</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002451" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002451</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002451" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002451</a>]</span><br /> -
Abnormal 'hobby horse' ataxic gait <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805535&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805535</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> VOICE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Whispering dysphonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3549680&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3549680</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset between 13 to 37 years<br /> -
Favorable response to alcohol<br /> -
One large family has been reported (last curated June 2013)<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the tubulin, beta-4A gene (TUBB4A, <a href="/entry/602662#0001">602662.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Dystonia
- <a href="/phenotypicSeries/PS128100">PS128100</a>
- 37 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/65?start=-3&limit=10&highlight=65"> 1p36.32-p36.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607671"> Dystonia 13, torsion </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607671"> 607671 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607671"> DYT13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607671"> 607671 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/373?start=-3&limit=10&highlight=373"> 1p35.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617282"> Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617282"> 617282 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608205"> MECR </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608205"> 608205 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/409?start=-3&limit=10&highlight=409"> 1p35.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/224500"> Dystonia 2, torsion, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/224500"> 224500 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/142622"> HPCA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/142622"> 142622 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/513?start=-3&limit=10&highlight=513"> 1p34.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612126"> GLUT1 deficiency syndrome 2, childhood onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612126"> 612126 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/138140"> SLC2A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/138140"> 138140 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/513?start=-3&limit=10&highlight=513"> 1p34.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601042"> Dystonia 9 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601042"> 601042 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/138140"> SLC2A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/138140"> 138140 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/185?start=-3&limit=10&highlight=185"> 2p22.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619687"> Dystonia 33 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619687"> 619687 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176871"> EIF2AK2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176871"> 176871 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/614?start=-3&limit=10&highlight=614"> 2q14.3-q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614588"> Dystonia 21 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614588"> 614588 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614588"> DYT21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614588"> 614588 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/751?start=-3&limit=10&highlight=751"> 2q31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611147"> Paroxysmal nonkinesigenic dyskinesia 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611147"> 611147 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611147"> PNKD2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611147"> 611147 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/819?start=-3&limit=10&highlight=819"> 2q31.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612067"> Dystonia 16 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612067"> 612067 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603424"> PRKRA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603424"> 603424 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/1003?start=-3&limit=10&highlight=1003"> 2q35 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/118800"> Paroxysmal nonkinesigenic dyskinesia 1 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/118800"> 118800 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609023"> PNKD </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609023"> 609023 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/1149?start=-3&limit=10&highlight=1149"> 2q37.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616411"> Dystonia 27 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616411"> 616411 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120250"> COL6A3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120250"> 120250 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/461?start=-3&limit=10&highlight=461"> 3p13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619921"> ?Dystonia 35, childhood-onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619921"> 619921 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613663"> SHQ1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613663"> 613663 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/339?start=-3&limit=10&highlight=339"> 4q21.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620427"> Dystonia 37, early-onset, with striatal lesions </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620427"> 620427 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607607"> NUP54 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607607"> 607607 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/376?start=-3&limit=10&highlight=376"> 5q22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619724"> ?Dystonia 34, myoclonic </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619724"> 619724 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605879"> KCNN2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605879"> 605879 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/425?start=-3&limit=10&highlight=425"> 7q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/159900"> Dystonia-11, myoclonic </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/159900"> 159900 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604149"> SGCE </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604149"> 604149 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/239?start=-3&limit=10&highlight=239"> 8p11.21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602629"> Dystonia 6, torsion </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602629"> 602629 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609520"> THAP1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609520"> 609520 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/326?start=-3&limit=10&highlight=326"> 9q22.32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619565"> Dystonia 31 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619565"> 619565 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619600"> AOPEP </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619600"> 619600 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/514?start=-3&limit=10&highlight=514"> 9q34 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614860"> Dystonia 23 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614860"> 614860 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614860"> DYT23 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614860"> 614860 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/571?start=-3&limit=10&highlight=571"> 9q34.11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128100"> Dystonia-1, torsion </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128100"> 128100 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605204"> TOR1A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605204"> 605204 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/249?start=-3&limit=10&highlight=249"> 11p14.3-p14.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615034"> Dystonia 24 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615034"> 615034 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610110"> ANO3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610110"> 610110 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/629?start=-3&limit=10&highlight=629"> 11q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620245"> Episodic kinesigenic dyskinesia 3 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620245"> 620245 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620108"> TMEM151A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620108"> 620108 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/1003?start=-3&limit=10&highlight=1003"> 11q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619637"> ?Dystonia 32 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619637"> 619637 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608549"> VPS11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608549"> 608549 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/14/252?start=-3&limit=10&highlight=252"> 14q22.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128230"> Dystonia, DOPA-responsive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128230"> 128230 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600225"> GCH1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600225"> 600225 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/330?start=-3&limit=10&highlight=330"> 16p11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128200"> Episodic kinesigenic dyskinesia 1 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128200"> 128200 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614386"> PRRT2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614386"> 614386 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/449?start=-3&limit=10&highlight=449"> 16q13-q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611031"> Episodic kinesigenic dyskinesia 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611031"> 611031 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611031"> EKD2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611031"> 611031 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/784?start=-3&limit=10&highlight=784"> 17q22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620456"> ?Dystonia 22, adult-onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620456"> 620456 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610764"> TSPOAP1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610764"> 610764 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/784?start=-3&limit=10&highlight=784"> 17q22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620453"> Dystonia 22, juvenile-onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620453"> 620453 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610764"> TSPOAP1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610764"> 610764 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/18/4?start=-3&limit=10&highlight=4"> 18p11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607488"> Dystonia-15, myoclonic </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607488"> 607488 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607488"> DYT15 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607488"> 607488 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/18/5?start=-3&limit=10&highlight=5"> 18p </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602124"> Dystonia-7, torsion </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602124"> 602124 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602124"> DYT7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602124"> 602124 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/18/57?start=-3&limit=10&highlight=57"> 18p11.21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615073"> Dystonia 25 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615073"> 615073 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/139312"> GNAL </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/139312"> 139312 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/185?start=-3&limit=10&highlight=185"> 19p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128101"> Dystonia 4, torsion, autosomal dominant </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128101"> 128101 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602662"> TUBB4A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602662"> 602662 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/595?start=-3&limit=10&highlight=595"> 19q13.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617284"> Dystonia 28, childhood-onset </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617284"> 617284 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606834"> KMT2B </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606834"> 606834 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/745?start=-3&limit=10&highlight=745"> 19q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128235"> Dystonia-12 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/128235"> 128235 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/182350"> ATP1A3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/182350"> 182350 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/20/40?start=-3&limit=10&highlight=40"> 20p13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619291"> Dystonia 30 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619291"> 619291 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608550"> VPS16 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608550"> 608550 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/20/116?start=-3&limit=10&highlight=116"> 20p11.2-q13.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612406"> Dystonia-17, primary torsion </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="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612406"> 612406 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612406"> DYT17 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612406"> 612406 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/22/234?start=-3&limit=10&highlight=234"> 22q12.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616398"> Dystonia 26, myoclonic </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616398"> 616398 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616386"> KCTD17 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616386"> 616386 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/411?start=-3&limit=10&highlight=411"> Xq13.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/314250"> Dystonia-Parkinsonism, X-linked </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/314250"> 314250 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/313650"> TAF1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/313650"> 313650 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
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<p>A number sign (#) is used with this entry because of evidence that autosomal dominant torsion dystonia-4 (DYT4) is caused by heterozygous mutation in the TUBB4A gene (<a href="/entry/602662">602662</a>) on chromosome 19p13.</p><p>Mutation in the TUBB4A gene can also cause hypomyelinating leukodystrophy-6 (HLD6; <a href="/entry/612438">612438</a>), a more severe disorder.</p>
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<p>Dystonia-4 (DYT4), also known as whispering dysphonia, is an autosomal dominant neurologic disorder characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait (summary by <a href="#3" class="mim-tip-reference" title="Hersheson, J., Mencacci, N. E., Davis, M., MacDonald, N., Trabzuni, D., Ryten, M., Pittman, A., Paudel, R., Kara, E., Fawcett, K., Plagnol, V., Bhatia, K. P., Medlar, A. J., Stanescu, H. C., Hardy, J., Kleta, R., Wood, N. W., Houlden, H. &lt;strong&gt;Mutations in the autoregulatory domain of beta-tubulin 4a cause hereditary dystonia.&lt;/strong&gt; Ann. Neurol. 73: 546-553, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23424103/&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;23424103&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23424103[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/10.1002/ana.23832&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="23424103">Hersheson et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23424103" 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="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a> described an extensive Australian kindred in which persons through 4 generations and by implication a fifth had torsion dystonia manifested mainly by a whispering dysphonia. They were able to shout and yell when emotional, had no trouble communicating after drinking alcohol, and talked normally in their sleep, yet when they tried under most circumstances to speak their voices came out only in a faint whisper. The ailment sometimes progressed to the point that the affected persons were unable to utter a sound when trying to speak. In some persons the whispering dysphonia continued throughout life as an isolated feature but more commonly it was the initial presentation of a 'more pervasive disease with extremely varied expression.' One living affected person with involuntary movements had classical findings of idiopathic dystonia musculorum deformans. At least 3 deceased members had been diagnosed as having Huntington disease. Others had isolated dystonic features, particularly torticollis and spastic dysphonia. The kindred contained a brother and sister with Wilson disease (<a href="/entry/277900">277900</a>). The occurrence of Wilson disease in the same kindred may have been coincidental. <a href="#1" class="mim-tip-reference" title="Ahmad, F., Davis, M. B., Waddy, H. M., Oley, C. A., Marsden, C. D., Harding, A. E. &lt;strong&gt;Evidence for locus heterogeneity in autosomal dominant torsion dystonia.&lt;/strong&gt; Genomics 15: 9-12, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8432555/&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;8432555&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1993.1003&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="8432555">Ahmad et al. (1993)</a> provided a follow-up of the family reported by <a href="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a>, which then contained affected members in 5 generations. The onset of symptoms ranged from 13 to 37 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8432555+3156966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Wilcox, R. A., Winkler, S., Lohmann, K., Klein, C. &lt;strong&gt;Whispering dysphonia in an Australian family (DYT4): a clinical and genetic reappraisal.&lt;/strong&gt; Mov. Disord. 26: 2404-2408, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21956287/&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;21956287&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/mds.23866&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="21956287">Wilcox et al. (2011)</a> provided another follow-up of the family reported by <a href="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a>. Affected family members tended to have a thin face and body habitus, even before the development of any speech or swallowing problems. Soon after the onset of spasmodic dysphonia, the cheeks became hollowed, the lower face tapered to the chin, the tongue became bradykinetic and showed poor motor patterning, and the mouth was open. All patients had laryngeal adductor dysphonia, which was responsive to alcohol. Several patients developed generalized dystonia or an unusual 'hobby horse gait,' with toe walking, stiff legs, and skipping gait. Brain MRI was unremarkable. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21956287+3156966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Bally, J. F., Camargos, S., Oliveira Dos Santos, C., Kern, D. S., Lee, T., Pereira da Silva-Junior, F., Puga, R. D., Cardoso, F., Barbosa, E. R., Yadav, R., Ozelius, L. J., de Carvalho Aguiar, P., Lang, A. E. DYT-TUBB4A (DYT4 dystonia). &lt;strong&gt;new clinical and genetic observations.&lt;/strong&gt; Neurology 96: e1887-e1897, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/32943487/&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;32943487&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=32943487[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/10.1212/WNL.0000000000010882&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="32943487">Bally et al. (2021)</a> reported 11 family members from 4 families with DYT4. The dystonia ranged from mild to very severe (death at age 13 years). Mean and median ages of onset were 17 and 21 years, respectively (range 2-30 years). The site of onset was most often the larynx (in 6), followed by arm (in 5) and neck (in 4). Nearly all patients (9 of 11) developed laryngeal involvement. Generalized dystonia was seen in 8 of the 11 patients. The rate of progression varied markedly among the patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32943487" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The pedigree pattern of the Australian family with dystonia reported by <a href="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a> was consistent with autosomal dominant inheritance. <a href="#1" class="mim-tip-reference" title="Ahmad, F., Davis, M. B., Waddy, H. M., Oley, C. A., Marsden, C. D., Harding, A. E. &lt;strong&gt;Evidence for locus heterogeneity in autosomal dominant torsion dystonia.&lt;/strong&gt; Genomics 15: 9-12, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8432555/&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;8432555&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1993.1003&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="8432555">Ahmad et al. (1993)</a> noted that no male-to-male transmission had occurred in the family. Among patients' offspring over the age of 40 years, the ratio of affected to unaffected subjects was 21:31 (40.4% affected). Nine of 22 affected members were male. Only 2 of the males had children: 2 sons and 4 daughters, of whom only 1 daughter was affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8432555+3156966" 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>By linkage analysis of the large family with DYT4 originally reported by <a href="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a>, <a href="#3" class="mim-tip-reference" title="Hersheson, J., Mencacci, N. E., Davis, M., MacDonald, N., Trabzuni, D., Ryten, M., Pittman, A., Paudel, R., Kara, E., Fawcett, K., Plagnol, V., Bhatia, K. P., Medlar, A. J., Stanescu, H. C., Hardy, J., Kleta, R., Wood, N. W., Houlden, H. &lt;strong&gt;Mutations in the autoregulatory domain of beta-tubulin 4a cause hereditary dystonia.&lt;/strong&gt; Ann. Neurol. 73: 546-553, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23424103/&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;23424103&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23424103[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/10.1002/ana.23832&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="23424103">Hersheson et al. (2013)</a> found linkage to chromosome 19p13.12 between <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs12977803;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs12977803</a> and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2303099;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs2303099</a> (maximum multipoint lod score of 6.33). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23424103+3156966" 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 members of the large multigenerational family of English and Australian origin with dystonia and Wilson disease originally reported by <a href="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a>, <a href="#7" class="mim-tip-reference" title="Wilcox, R. A., Winkler, S., Lohmann, K., Klein, C. &lt;strong&gt;Whispering dysphonia in an Australian family (DYT4): a clinical and genetic reappraisal.&lt;/strong&gt; Mov. Disord. 26: 2404-2408, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21956287/&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;21956287&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/mds.23866&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="21956287">Wilcox et al. (2011)</a> identified mutations in the ATP7B gene (<a href="/entry/606882">606882</a>), thus explaining the Wilson disease phenotype in the family. The ATP7B mutations did not segregate with the dystonia phenotype, confirming 2 genetic disorders in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21956287+3156966" 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 affected members of the family with dystonia originally reported by <a href="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a>, <a href="#3" class="mim-tip-reference" title="Hersheson, J., Mencacci, N. E., Davis, M., MacDonald, N., Trabzuni, D., Ryten, M., Pittman, A., Paudel, R., Kara, E., Fawcett, K., Plagnol, V., Bhatia, K. P., Medlar, A. J., Stanescu, H. C., Hardy, J., Kleta, R., Wood, N. W., Houlden, H. &lt;strong&gt;Mutations in the autoregulatory domain of beta-tubulin 4a cause hereditary dystonia.&lt;/strong&gt; Ann. Neurol. 73: 546-553, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23424103/&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;23424103&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23424103[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/10.1002/ana.23832&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="23424103">Hersheson et al. (2013)</a> identified a heterozygous mutation in the TUBB4A gene (R2G; <a href="/entry/602662#0001">602662.0001</a>). The mutation, which was found by linkage analysis and exome sequencing, was not found in several large control databases and segregated with dystonia in the family. Previous site-directed mutagenesis studies by <a href="#8" class="mim-tip-reference" title="Yen, T. J., Machlin, P. S., Cleveland, D. W. &lt;strong&gt;Autoregulated instability of beta-tubulin mRNAs by recognition of the nascent amino terminus of beta-tubulin.&lt;/strong&gt; Nature 334: 580-585, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3405308/&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;3405308&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/334580a0&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="3405308">Yen et al. (1988)</a> had shown that mutations in the MREI domain of TUBB4A, including R2G, abrogate the autoregulatory capability of TUBB4A, which may affect the balance of tubulin subunits and interfere with proper assembly. The findings suggested a role for the cytoskeleton in dystonia pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3405308+23424103+3156966" 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>Independently and simultaneously, <a href="#5" class="mim-tip-reference" title="Lohmann, K., Wilcox, R. A., Winkler, S., Ramirez, A., Rakovic, A., Park, J.-S., Arns, B., Lohnau, T., Groen, J., Kasten, M., Bruggemann, N., Hagenah, J., and 17 others. &lt;strong&gt;Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene.&lt;/strong&gt; Ann. Neurol. 73: 537-545, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23595291/&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;23595291&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23595291[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/10.1002/ana.23829&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="23595291">Lohmann et al. (2013)</a> identified a heterozygous R2G mutation in the TUBB4A gene in affected members of the family with DYT4 originally reported by <a href="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a>. The mutation was found by genomewide linkage analysis combined with genome sequencing in 2 family members. The mutation was confirmed by Sanger sequencing, segregated with the disorder in the family, and was not present in 1,000 control chromosomes or in the Exome Variant Server database. Primary cells from 1 of the mutation carriers showed decreased levels of mutant TUBB4A mRNA compared to controls, suggesting that the pathogenesis involved reduced levels of TUBB4. Screening of the TUBB4A gene in 394 unrelated patients with dystonia revealed a different heterozygous missense variant (A271T; <a href="/entry/602662#0003">602662.0003</a>) in a woman with onset of spasmodic dysphonia at age 60 years; functional studies of this variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23595291+3156966" 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 4 families with 11 family members with autosomal dominant dystonia, <a href="#2" class="mim-tip-reference" title="Bally, J. F., Camargos, S., Oliveira Dos Santos, C., Kern, D. S., Lee, T., Pereira da Silva-Junior, F., Puga, R. D., Cardoso, F., Barbosa, E. R., Yadav, R., Ozelius, L. J., de Carvalho Aguiar, P., Lang, A. E. DYT-TUBB4A (DYT4 dystonia). &lt;strong&gt;new clinical and genetic observations.&lt;/strong&gt; Neurology 96: e1887-e1897, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/32943487/&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;32943487&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=32943487[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/10.1212/WNL.0000000000010882&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="32943487">Bally et al. (2021)</a> used next-generation sequencing with a dystonia gene panel or whole-exome sequencing to identify 4 novel heterozygous missense variants in the TUBB4A gene (<a href="/entry/602662">602662</a>) (D295N, R46M, Q424H, and R121W). Variants segregated with disease in 3 of the families, with evidence for incomplete penetrance in 2 of them; in the fourth family, 1 affected and 4 unaffected members carried the variant (D295N). All variants changed highly conserved amino acids. No functional studies were performed, but all variants were predicted to be deleterious by in silico analysis. All were confirmed by Sanger sequencing, and none was seen in population databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32943487" 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="#1" class="mim-tip-reference" title="Ahmad, F., Davis, M. B., Waddy, H. M., Oley, C. A., Marsden, C. D., Harding, A. E. &lt;strong&gt;Evidence for locus heterogeneity in autosomal dominant torsion dystonia.&lt;/strong&gt; Genomics 15: 9-12, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8432555/&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;8432555&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1993.1003&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="8432555">Ahmad et al. (1993)</a> performed linkage studies in the large Australian pedigree originally reported by <a href="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a> and excluded location of the responsible locus (here symbolized DYT4) on 9q (see DYT1, <a href="/entry/128100">128100</a>). Investigation for linkage using markers flanking the Wilson disease locus likewise yielded negative results, thus excluding the possibility that the disorder was due to an allele at the WND locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8432555+3156966" 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 family with dystonia reported by <a href="#6" class="mim-tip-reference" title="Parker, N. &lt;strong&gt;Hereditary whispering dysphonia.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3156966/&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;3156966&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.48.3.218&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="3156966">Parker (1985)</a>, <a href="#4" class="mim-tip-reference" title="Jarman, P. R., del Grosso, N., Valente, E. M., Leube, B., Cassetta, E., Bentivoglio, A. R., Waddy, H. M., Uitti, R. J., Maraganore, D. M., Albanese, A., Frontali, M., Auburger, G., Bressman, S. B., Wood, N. W., Nygaard, T. G. &lt;strong&gt;Primary torsion dystonia: the search for genes is not over.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 67: 395-397, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10449567/&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;10449567&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.67.3.395&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="10449567">Jarman et al. (1999)</a> excluded linkage to selected markers on chromosomes 8 and 18. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10449567+3156966" 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="Ahmad1993" class="mim-anchor"></a>
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Ahmad, F., Davis, M. B., Waddy, H. M., Oley, C. A., Marsden, C. D., Harding, A. E.
<strong>Evidence for locus heterogeneity in autosomal dominant torsion dystonia.</strong>
Genomics 15: 9-12, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432555</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432555" 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.1993.1003" target="_blank">Full Text</a>]
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<a id="Bally2021" class="mim-anchor"></a>
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Bally, J. F., Camargos, S., Oliveira Dos Santos, C., Kern, D. S., Lee, T., Pereira da Silva-Junior, F., Puga, R. D., Cardoso, F., Barbosa, E. R., Yadav, R., Ozelius, L. J., de Carvalho Aguiar, P., Lang, A. E. DYT-TUBB4A (DYT4 dystonia).
<strong>new clinical and genetic observations.</strong>
Neurology 96: e1887-e1897, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32943487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32943487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32943487[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=32943487" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0000000000010882" target="_blank">Full Text</a>]
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<a id="Hersheson2013" class="mim-anchor"></a>
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Hersheson, J., Mencacci, N. E., Davis, M., MacDonald, N., Trabzuni, D., Ryten, M., Pittman, A., Paudel, R., Kara, E., Fawcett, K., Plagnol, V., Bhatia, K. P., Medlar, A. J., Stanescu, H. C., Hardy, J., Kleta, R., Wood, N. W., Houlden, H.
<strong>Mutations in the autoregulatory domain of beta-tubulin 4a cause hereditary dystonia.</strong>
Ann. Neurol. 73: 546-553, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23424103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23424103</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23424103[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=23424103" 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.23832" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
<a id="Jarman1999" class="mim-anchor"></a>
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<p class="mim-text-font">
Jarman, P. R., del Grosso, N., Valente, E. M., Leube, B., Cassetta, E., Bentivoglio, A. R., Waddy, H. M., Uitti, R. J., Maraganore, D. M., Albanese, A., Frontali, M., Auburger, G., Bressman, S. B., Wood, N. W., Nygaard, T. G.
<strong>Primary torsion dystonia: the search for genes is not over.</strong>
J. Neurol. Neurosurg. Psychiat. 67: 395-397, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10449567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10449567</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10449567" 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/jnnp.67.3.395" target="_blank">Full Text</a>]
</p>
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<a id="5" class="mim-anchor"></a>
<a id="Lohmann2013" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lohmann, K., Wilcox, R. A., Winkler, S., Ramirez, A., Rakovic, A., Park, J.-S., Arns, B., Lohnau, T., Groen, J., Kasten, M., Bruggemann, N., Hagenah, J., and 17 others.
<strong>Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene.</strong>
Ann. Neurol. 73: 537-545, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23595291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23595291</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23595291[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=23595291" 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.23829" target="_blank">Full Text</a>]
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<a id="Parker1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Parker, N.
<strong>Hereditary whispering dysphonia.</strong>
J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3156966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3156966</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3156966" 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/jnnp.48.3.218" target="_blank">Full Text</a>]
</p>
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<a id="Wilcox2011" class="mim-anchor"></a>
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<p class="mim-text-font">
Wilcox, R. A., Winkler, S., Lohmann, K., Klein, C.
<strong>Whispering dysphonia in an Australian family (DYT4): a clinical and genetic reappraisal.</strong>
Mov. Disord. 26: 2404-2408, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21956287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21956287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21956287" 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.23866" target="_blank">Full Text</a>]
</p>
</div>
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<a id="8" class="mim-anchor"></a>
<a id="Yen1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Yen, T. J., Machlin, P. S., Cleveland, D. W.
<strong>Autoregulated instability of beta-tubulin mRNAs by recognition of the nascent amino terminus of beta-tubulin.</strong>
Nature 334: 580-585, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3405308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3405308</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3405308" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/334580a0" target="_blank">Full Text</a>]
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Sonja A. Rasmussen - updated : 07/07/2022
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Cassandra L. Kniffin - updated : 12/30/2013<br>Cassandra L. Kniffin - updated : 6/10/2013<br>Carol A. Bocchini - updated : 2/14/2013
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Victor A. McKusick : 2/11/1993
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carol : 08/06/2024
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alopez : 07/07/2022<br>carol : 01/06/2014<br>ckniffin : 12/30/2013<br>carol : 6/20/2013<br>ckniffin : 6/10/2013<br>carol : 2/14/2013<br>carol : 2/14/2013<br>wwang : 11/25/2008<br>carol : 3/18/2004<br>dkim : 9/9/1998<br>mimadm : 6/25/1994<br>carol : 2/11/1993
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<h3>
<span class="mim-font">
<strong>#</strong> 128101
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<span class="mim-font">
DYSTONIA 4, TORSION, AUTOSOMAL DOMINANT; DYT4
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<span class="mim-font">
<em>Alternative titles; symbols</em>
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WHISPERING DYSPHONIA, HEREDITARY<br />
DYSTONIA MUSCULORUM DEFORMANS 4
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<strong>ORPHA:</strong> 98805; &nbsp;
<strong>DO:</strong> 0090041; &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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<span class="mim-font">
19p13.3
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Dystonia 4, torsion, autosomal dominant
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128101
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Autosomal dominant
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3
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TUBB4A
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602662
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<span class="mim-font">
<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that autosomal dominant torsion dystonia-4 (DYT4) is caused by heterozygous mutation in the TUBB4A gene (602662) on chromosome 19p13.</p><p>Mutation in the TUBB4A gene can also cause hypomyelinating leukodystrophy-6 (HLD6; 612438), a more severe disorder.</p>
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<strong>Description</strong>
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<p>Dystonia-4 (DYT4), also known as whispering dysphonia, is an autosomal dominant neurologic disorder characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait (summary by Hersheson et al., 2013). </p>
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<span class="mim-font">
<strong>Clinical Features</strong>
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<p>Parker (1985) described an extensive Australian kindred in which persons through 4 generations and by implication a fifth had torsion dystonia manifested mainly by a whispering dysphonia. They were able to shout and yell when emotional, had no trouble communicating after drinking alcohol, and talked normally in their sleep, yet when they tried under most circumstances to speak their voices came out only in a faint whisper. The ailment sometimes progressed to the point that the affected persons were unable to utter a sound when trying to speak. In some persons the whispering dysphonia continued throughout life as an isolated feature but more commonly it was the initial presentation of a 'more pervasive disease with extremely varied expression.' One living affected person with involuntary movements had classical findings of idiopathic dystonia musculorum deformans. At least 3 deceased members had been diagnosed as having Huntington disease. Others had isolated dystonic features, particularly torticollis and spastic dysphonia. The kindred contained a brother and sister with Wilson disease (277900). The occurrence of Wilson disease in the same kindred may have been coincidental. Ahmad et al. (1993) provided a follow-up of the family reported by Parker (1985), which then contained affected members in 5 generations. The onset of symptoms ranged from 13 to 37 years. </p><p>Wilcox et al. (2011) provided another follow-up of the family reported by Parker (1985). Affected family members tended to have a thin face and body habitus, even before the development of any speech or swallowing problems. Soon after the onset of spasmodic dysphonia, the cheeks became hollowed, the lower face tapered to the chin, the tongue became bradykinetic and showed poor motor patterning, and the mouth was open. All patients had laryngeal adductor dysphonia, which was responsive to alcohol. Several patients developed generalized dystonia or an unusual 'hobby horse gait,' with toe walking, stiff legs, and skipping gait. Brain MRI was unremarkable. </p><p>Bally et al. (2021) reported 11 family members from 4 families with DYT4. The dystonia ranged from mild to very severe (death at age 13 years). Mean and median ages of onset were 17 and 21 years, respectively (range 2-30 years). The site of onset was most often the larynx (in 6), followed by arm (in 5) and neck (in 4). Nearly all patients (9 of 11) developed laryngeal involvement. Generalized dystonia was seen in 8 of the 11 patients. The rate of progression varied markedly among the patients. </p>
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<strong>Inheritance</strong>
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<p>The pedigree pattern of the Australian family with dystonia reported by Parker (1985) was consistent with autosomal dominant inheritance. Ahmad et al. (1993) noted that no male-to-male transmission had occurred in the family. Among patients' offspring over the age of 40 years, the ratio of affected to unaffected subjects was 21:31 (40.4% affected). Nine of 22 affected members were male. Only 2 of the males had children: 2 sons and 4 daughters, of whom only 1 daughter was affected. </p>
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<h4>
<span class="mim-font">
<strong>Mapping</strong>
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<p>By linkage analysis of the large family with DYT4 originally reported by Parker (1985), Hersheson et al. (2013) found linkage to chromosome 19p13.12 between rs12977803 and rs2303099 (maximum multipoint lod score of 6.33). </p>
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<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
<p>In members of the large multigenerational family of English and Australian origin with dystonia and Wilson disease originally reported by Parker (1985), Wilcox et al. (2011) identified mutations in the ATP7B gene (606882), thus explaining the Wilson disease phenotype in the family. The ATP7B mutations did not segregate with the dystonia phenotype, confirming 2 genetic disorders in the family. </p><p>In affected members of the family with dystonia originally reported by Parker (1985), Hersheson et al. (2013) identified a heterozygous mutation in the TUBB4A gene (R2G; 602662.0001). The mutation, which was found by linkage analysis and exome sequencing, was not found in several large control databases and segregated with dystonia in the family. Previous site-directed mutagenesis studies by Yen et al. (1988) had shown that mutations in the MREI domain of TUBB4A, including R2G, abrogate the autoregulatory capability of TUBB4A, which may affect the balance of tubulin subunits and interfere with proper assembly. The findings suggested a role for the cytoskeleton in dystonia pathogenesis. </p><p>Independently and simultaneously, Lohmann et al. (2013) identified a heterozygous R2G mutation in the TUBB4A gene in affected members of the family with DYT4 originally reported by Parker (1985). The mutation was found by genomewide linkage analysis combined with genome sequencing in 2 family members. The mutation was confirmed by Sanger sequencing, segregated with the disorder in the family, and was not present in 1,000 control chromosomes or in the Exome Variant Server database. Primary cells from 1 of the mutation carriers showed decreased levels of mutant TUBB4A mRNA compared to controls, suggesting that the pathogenesis involved reduced levels of TUBB4. Screening of the TUBB4A gene in 394 unrelated patients with dystonia revealed a different heterozygous missense variant (A271T; 602662.0003) in a woman with onset of spasmodic dysphonia at age 60 years; functional studies of this variant were not performed. </p><p>In 4 families with 11 family members with autosomal dominant dystonia, Bally et al. (2021) used next-generation sequencing with a dystonia gene panel or whole-exome sequencing to identify 4 novel heterozygous missense variants in the TUBB4A gene (602662) (D295N, R46M, Q424H, and R121W). Variants segregated with disease in 3 of the families, with evidence for incomplete penetrance in 2 of them; in the fourth family, 1 affected and 4 unaffected members carried the variant (D295N). All variants changed highly conserved amino acids. No functional studies were performed, but all variants were predicted to be deleterious by in silico analysis. All were confirmed by Sanger sequencing, and none was seen in population databases. </p>
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<strong>History</strong>
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<p>Ahmad et al. (1993) performed linkage studies in the large Australian pedigree originally reported by Parker (1985) and excluded location of the responsible locus (here symbolized DYT4) on 9q (see DYT1, 128100). Investigation for linkage using markers flanking the Wilson disease locus likewise yielded negative results, thus excluding the possibility that the disorder was due to an allele at the WND locus. </p><p>In the family with dystonia reported by Parker (1985), Jarman et al. (1999) excluded linkage to selected markers on chromosomes 8 and 18. </p>
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<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Ahmad, F., Davis, M. B., Waddy, H. M., Oley, C. A., Marsden, C. D., Harding, A. E.
<strong>Evidence for locus heterogeneity in autosomal dominant torsion dystonia.</strong>
Genomics 15: 9-12, 1993.
[PubMed: 8432555]
[Full Text: https://doi.org/10.1006/geno.1993.1003]
</p>
</li>
<li>
<p class="mim-text-font">
Bally, J. F., Camargos, S., Oliveira Dos Santos, C., Kern, D. S., Lee, T., Pereira da Silva-Junior, F., Puga, R. D., Cardoso, F., Barbosa, E. R., Yadav, R., Ozelius, L. J., de Carvalho Aguiar, P., Lang, A. E. DYT-TUBB4A (DYT4 dystonia).
<strong>new clinical and genetic observations.</strong>
Neurology 96: e1887-e1897, 2021.
[PubMed: 32943487]
[Full Text: https://doi.org/10.1212/WNL.0000000000010882]
</p>
</li>
<li>
<p class="mim-text-font">
Hersheson, J., Mencacci, N. E., Davis, M., MacDonald, N., Trabzuni, D., Ryten, M., Pittman, A., Paudel, R., Kara, E., Fawcett, K., Plagnol, V., Bhatia, K. P., Medlar, A. J., Stanescu, H. C., Hardy, J., Kleta, R., Wood, N. W., Houlden, H.
<strong>Mutations in the autoregulatory domain of beta-tubulin 4a cause hereditary dystonia.</strong>
Ann. Neurol. 73: 546-553, 2013.
[PubMed: 23424103]
[Full Text: https://doi.org/10.1002/ana.23832]
</p>
</li>
<li>
<p class="mim-text-font">
Jarman, P. R., del Grosso, N., Valente, E. M., Leube, B., Cassetta, E., Bentivoglio, A. R., Waddy, H. M., Uitti, R. J., Maraganore, D. M., Albanese, A., Frontali, M., Auburger, G., Bressman, S. B., Wood, N. W., Nygaard, T. G.
<strong>Primary torsion dystonia: the search for genes is not over.</strong>
J. Neurol. Neurosurg. Psychiat. 67: 395-397, 1999.
[PubMed: 10449567]
[Full Text: https://doi.org/10.1136/jnnp.67.3.395]
</p>
</li>
<li>
<p class="mim-text-font">
Lohmann, K., Wilcox, R. A., Winkler, S., Ramirez, A., Rakovic, A., Park, J.-S., Arns, B., Lohnau, T., Groen, J., Kasten, M., Bruggemann, N., Hagenah, J., and 17 others.
<strong>Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene.</strong>
Ann. Neurol. 73: 537-545, 2013.
[PubMed: 23595291]
[Full Text: https://doi.org/10.1002/ana.23829]
</p>
</li>
<li>
<p class="mim-text-font">
Parker, N.
<strong>Hereditary whispering dysphonia.</strong>
J. Neurol. Neurosurg. Psychiat. 48: 218-224, 1985.
[PubMed: 3156966]
[Full Text: https://doi.org/10.1136/jnnp.48.3.218]
</p>
</li>
<li>
<p class="mim-text-font">
Wilcox, R. A., Winkler, S., Lohmann, K., Klein, C.
<strong>Whispering dysphonia in an Australian family (DYT4): a clinical and genetic reappraisal.</strong>
Mov. Disord. 26: 2404-2408, 2011.
[PubMed: 21956287]
[Full Text: https://doi.org/10.1002/mds.23866]
</p>
</li>
<li>
<p class="mim-text-font">
Yen, T. J., Machlin, P. S., Cleveland, D. W.
<strong>Autoregulated instability of beta-tubulin mRNAs by recognition of the nascent amino terminus of beta-tubulin.</strong>
Nature 334: 580-585, 1988.
[PubMed: 3405308]
[Full Text: https://doi.org/10.1038/334580a0]
</p>
</li>
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Contributors:
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Sonja A. Rasmussen - updated : 07/07/2022<br>Cassandra L. Kniffin - updated : 12/30/2013<br>Cassandra L. Kniffin - updated : 6/10/2013<br>Carol A. Bocchini - updated : 2/14/2013
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Creation Date:
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Victor A. McKusick : 2/11/1993
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carol : 08/06/2024<br>alopez : 07/07/2022<br>carol : 01/06/2014<br>ckniffin : 12/30/2013<br>carol : 6/20/2013<br>ckniffin : 6/10/2013<br>carol : 2/14/2013<br>carol : 2/14/2013<br>wwang : 11/25/2008<br>carol : 3/18/2004<br>dkim : 9/9/1998<br>mimadm : 6/25/1994<br>carol : 2/11/1993
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