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<title>
Entry
- #600223 - SPINOCEREBELLAR ATAXIA 4; SCA4
- OMIM
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<span class="h4">#600223</span>
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<strong>Table of Contents</strong>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/600223"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS164400"> <strong>Phenotypic Series</strong> </a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<div><a href="https://clinicaltrials.gov/search?cond=SPINOCEREBELLAR ATAXIA" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="http://www.informatics.jax.org/disease/600223" 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:0050957" 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>SNOMEDCT:</strong> 715755008<br />
<strong>ORPHA:</strong> 98765<br />
<strong>DO:</strong> 0050957<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>
600223
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
SPINOCEREBELLAR ATAXIA 4; SCA4
</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">
SPINOCEREBELLAR ATAXIA, AUTOSOMAL DOMINANT, WITH SENSORY AXONAL NEUROPATHY
</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/16/630?start=-3&limit=10&highlight=630">
16q22.2-q22.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Spinocerebellar ataxia 4
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600223"> 600223 </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">
ZFHX3
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/104155"> 104155 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group mim-changed mim-change">
<a href="/clinicalSynopsis/600223" 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/PS164400" 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>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/600223" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/600223" 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> Weight </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Weight loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/89362005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">89362005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/816160009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">816160009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/262285001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">262285001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/161832001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">161832001</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.21</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3540682&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3540682</a>, <a href="https://bioportal.bioontology.org/search?q=C5203233&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5203233</a>, <a href="https://bioportal.bioontology.org/search?q=C1262477&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1262477</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001824" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001824</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001824" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001824</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Head tremor (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239882&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239882</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002346" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002346</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002346" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002346</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Facial twitching (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0858722&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0858722</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011468" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011468</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Slow saccades <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/404686001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">404686001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1321329&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1321329</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000514" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000514</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000514" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000514</a>]</span><br />
- Hypometric saccades <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246768008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246768008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423082&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423082</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000571" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000571</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000571" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000571</a>]</span><br />
- Impaired smooth pursuit <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837458&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837458</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007772" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007772</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007772" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007772</a>]</span><br />
<div class="mim-changed mim-change"> - Gaze-evoked nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1220537002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1220537002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5574666&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5574666</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000640" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000640</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000640" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000640</a>]</span><br /></div>
</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 (in some patients) <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> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Vascular </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Orthostatic hypotension <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/28651003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">28651003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I95.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I95.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/458.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">458.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020651&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020651</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001278</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001278</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
<div class="mim-changed mim-change"> - Chronic cough <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/68154008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">68154008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R05.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R05.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010201&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010201</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034315</a>]</span><br /></div>
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> 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 /> -
Swallowing difficulties <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 /> -
Constipation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14760008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14760008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/564.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/564.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009806&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009806</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span><br /> -
Diarrhea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267060006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267060006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62315008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62315008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R19.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R19.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011991&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011991</a>, <a href="https://bioportal.bioontology.org/search?q=C2169706&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2169706</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Bladder </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Urinary incontinence <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/165232002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">165232002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R32" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R32</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/788.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.30</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/788.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042024&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042024</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000020</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000020</a>]</span><br /> -
Urinary urgency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75088002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75088002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R39.15" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R39.15</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/788.63" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.63</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085606&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085606</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000012" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000012</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000012" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000012</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Leg cramps <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/449918009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">449918009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3266180&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3266180</a>, <a href="https://bioportal.bioontology.org/search?q=C0023218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023218</a>]</span><br /> -
Muscle wasting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88092000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88092000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541794&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541794</a>, <a href="https://bioportal.bioontology.org/search?q=C0026846&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026846</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span><br /> -
Fasciculations <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/82470000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">82470000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R25.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R25.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015644&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015644</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002380" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002380</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002380" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002380</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cerebellar ataxia, progressive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230233000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230233000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0393525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393525</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002073" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002073</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002073" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002073</a>]</span><br />
- Gait ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25136009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25136009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R26.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R26.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span><br />
- Unsteady gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22631008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22631008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231686</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002317" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002317</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002317" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002317</a>]</span><br />
- Loss of ambulation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836843&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836843</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002505</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002505</a>]</span><br />
- Difficulty with handwriting <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4313188&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4313188</a>]</span><br />
- Limb ataxia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0750937&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0750937</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002070" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002070</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002070" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002070</a>]</span><br />
- Limb dysmetria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854489&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854489</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002406" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002406</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002406" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002406</a>]</span><br />
- Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br />
- Poor coordination <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0563243&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0563243</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002370" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002370</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002370" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002370</a>]</span><br />
- Extensor plantar responses <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246586009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246586009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366575004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366575004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034935</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span><br />
- Restless legs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32914008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32914008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G25.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G25.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/333.94" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">333.94</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035258&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035258</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:5200426" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:5200426</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0012452" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012452</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012452" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012452</a>]</span><br />
- Involuntary twitching <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5883335&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5883335</a>]</span><br />
<div class="mim-changed mim-change"> - Exercise-induced dystonia<br /></div>
- Intention tremor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30721006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30721006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G25.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G25.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551520&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551520</a>, <a href="https://bioportal.bioontology.org/search?q=C0234376&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234376</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002345" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002345</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002080" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002080</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002080" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002080</a>]</span><br />
- Autonomic disturbances <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806648&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806648</a>]</span><br />
- Cerebellar atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740279</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Peripheral Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sensory or sensorimotor axonal peripheral neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5883336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5883336</a>]</span><br /> -
Distal sensory impairment <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847584&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847584</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002936</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002936</a>]</span><br /> -
Hyporeflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700078</a>, <a href="https://bioportal.bioontology.org/search?q=C0151888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br /> -
Areflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37280007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37280007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234146</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span><br /> -
Absent or reduced sural nerve sensory responses <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1838401&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1838401</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset in fourth or fifth decades (earlier onset has been reported)<br /> -
Progressive disorder <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864985&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864985</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span><br /> -
Genetic anticipation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0600498&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0600498</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003743" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003743</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003743" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003743</a>]</span><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 expanded trinucleotide repeat (GGCn) in the zinc finger homeobox 3 gene (ZFHX3, <a href="/entry/104155#0003">104155.0003</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>
Spinocerebellar ataxia
- <a href="/phenotypicSeries/PS164400">PS164400</a>
- 49 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/1/49?start=-3&limit=10&highlight=49"> 1p36.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607454"> Spinocerebellar ataxia 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="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607454"> 607454 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616101"> TMEM240 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616101"> 616101 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/378?start=-3&limit=10&highlight=378"> 1p35.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617931"> Spinocerebellar ataxia 47 </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/617931"> 617931 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607204"> PUM1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607204"> 607204 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/653?start=-3&limit=10&highlight=653"> 1p32.2-p32.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615945"> Spinocerebellar ataxia 37 </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/615945"> 615945 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603448"> DAB1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603448"> 603448 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/919?start=-3&limit=10&highlight=919"> 1p13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607346"> Spinocerebellar ataxia 19 </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/607346"> 607346 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605411"> KCND3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605411"> 605411 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/269?start=-3&limit=10&highlight=269"> 2p16.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608703"> Spinocerebellar ataxia 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/608703"> 608703 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610316"> PNPT1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610316"> 610316 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/17?start=-3&limit=10&highlight=17"> 3p26.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606658"> Spinocerebellar ataxia 15 </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/606658"> 606658 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/147265"> ITPR1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/147265"> 147265 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/17?start=-3&limit=10&highlight=17"> 3p26.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/117360"> Spinocerebellar ataxia 29, congenital nonprogressive </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/117360"> 117360 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/147265"> ITPR1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/147265"> 147265 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/436?start=-3&limit=10&highlight=436"> 3p14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164500"> Spinocerebellar ataxia 7 </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/164500"> 164500 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607640"> ATXN7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607640"> 607640 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/798?start=-3&limit=10&highlight=798"> 3q25.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617018"> ?Spinocerebellar ataxia 43 </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/617018"> 617018 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120520"> MME </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120520"> 120520 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/531?start=-3&limit=10&highlight=531"> 4q27 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616410"> ?Spinocerebellar ataxia 41 </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/616410"> 616410 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602345"> TRPC3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602345"> 602345 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/691?start=-3&limit=10&highlight=691"> 4q34.3-q35.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613371"> ?Spinocerebellar ataxia 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="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613371"> 613371 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613371"> SCA30 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613371"> 613371 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/633?start=-3&limit=10&highlight=633"> 5q32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604326"> Spinocerebellar ataxia 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/604326"> 604326 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604325"> PPP2R2B </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604325"> 604325 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/687?start=-3&limit=10&highlight=687"> 5q33.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617769"> Spinocerebellar ataxia 45 </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/617769"> 617769 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604269"> FAT2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604269"> 604269 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/90?start=-3&limit=10&highlight=90"> 6p22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164400"> Spinocerebellar ataxia 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/164400"> 164400 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601556"> ATXN1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601556"> 601556 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/600?start=-3&limit=10&highlight=600"> 6p12.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615957"> Spinocerebellar ataxia 38 </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/615957"> 615957 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611805"> ELOVL5 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611805"> 611805 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/667?start=-3&limit=10&highlight=667"> 6q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/133190"> Spinocerebellar ataxia 34 </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/133190"> 133190 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605512"> ELOVL4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605512"> 605512 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/928?start=-3&limit=10&highlight=928"> 6q24.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617691"> Spinocerebellar ataxia 44 </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/617691"> 617691 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604473"> GRM1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604473"> 604473 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/1041?start=-3&limit=10&highlight=1041"> 6q27 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607136"> Spinocerebellar ataxia 17 </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/607136"> 607136 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600075"> TBP </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600075"> 600075 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/414?start=-3&limit=10&highlight=414"> 7q21.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619806"> ?Spinocerebellar ataxia 49 </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/619806"> 619806 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611170"> SAMD9L </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611170"> 611170 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/454?start=-3&limit=10&highlight=454"> 7q22-q32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607458"> Spinocerebellar ataxia 18 </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/607458"> 607458 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607458"> SCA18 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607458"> 607458 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/642?start=-3&limit=10&highlight=642"> 7q32-q33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613909"> Spinocerebellar ataxia 32 </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/613909"> 613909 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613909"> SCA32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613909"> 613909 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/380?start=-3&limit=10&highlight=380"> 11q12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608687"> Spinocerebellar ataxia 20 </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="4 - A contiguous gene duplication or deletion syndrome in which multiple genes are involved"> 4 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608687"> 608687 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608687"> SCA20 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608687"> 608687 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/646?start=-3&limit=10&highlight=646"> 11q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600224"> Spinocerebellar ataxia 5 </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/600224"> 600224 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604985"> SPTBN2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604985"> 604985 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/813?start=-3&limit=10&highlight=813"> 12q24.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/183090"> Spinocerebellar ataxia 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="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/183090"> 183090 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601517"> ATXN2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601517"> 601517 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/813?start=-3&limit=10&highlight=813"> 12q24.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/183090"> {Amyotrophic lateral sclerosis, susceptibility to, 13} </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/183090"> 183090 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601517"> ATXN2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601517"> 601517 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/13/204?start=-3&limit=10&highlight=204"> 13q21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608768"> Spinocerebellar ataxia 8 </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/608768"> 608768 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613289"> ATXN8 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613289"> 613289 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/13/213?start=-3&limit=10&highlight=213"> 13q21.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608768"> Spinocerebellar ataxia 8 </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/608768"> 608768 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603680"> ATXN8OS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603680"> 603680 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/13/293?start=-3&limit=10&highlight=293"> 13q33.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/193003"> Spinocerebellar ataxia 27A </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/193003"> 193003 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601515"> FGF14 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601515"> 601515 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/13/293?start=-3&limit=10&highlight=293"> 13q33.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620174"> Spinocerebellar ataxia 27B, late-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/620174"> 620174 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601515"> FGF14 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601515"> 601515 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/14/460?start=-3&limit=10&highlight=460"> 14q32.11-q32.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616053"> ?Spinocerebellar ataxia 40 </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/616053"> 616053 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611204"> CCDC88C </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611204"> 611204 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/14/466?start=-3&limit=10&highlight=466"> 14q32.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/109150"> Machado-Joseph disease </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/109150"> 109150 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607047"> ATXN3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607047"> 607047 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/139?start=-3&limit=10&highlight=139"> 15q15.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604432"> Spinocerebellar ataxia 11 </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/604432"> 604432 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611695"> TTBK2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611695"> 611695 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/37?start=-3&limit=10&highlight=37"> 16p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618093"> Spinocerebellar ataxia 48 </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/618093"> 618093 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607207"> STUB1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607207"> 607207 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/510?start=-3&limit=10&highlight=510"> 16q21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/117210"> Spinocerebellar ataxia 31 </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/117210"> 117210 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612051"> BEAN1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612051"> 612051 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/561?start=-3&limit=10&highlight=561"> 16q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620947"> Spinocerebellar ataxia 51 </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/620947"> 620947 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609119"> THAP11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609119"> 609119 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/630?start=-3&limit=10&highlight=630"> 16q22.2-q22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600223"> Spinocerebellar ataxia 4 </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/600223"> 600223 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/104155"> ZFHX3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/104155"> 104155 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/747?start=-3&limit=10&highlight=747"> 17q21.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616795"> Spinocerebellar ataxia 42 </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/616795"> 616795 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604065"> CACNA1G </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604065"> 604065 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/1021?start=-3&limit=10&highlight=1021"> 17q25.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620158"> Spinocerebellar ataxia 50 </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/620158"> 620158 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602367"> NPTX1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602367"> 602367 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/18/63?start=-3&limit=10&highlight=63"> 18p11.21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610246"> Spinocerebellar ataxia 28 </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/610246"> 610246 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604581"> AFG3L2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604581"> 604581 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/123?start=-3&limit=10&highlight=123"> 19p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609306"> ?Spinocerebellar ataxia 26 </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/609306"> 609306 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130610"> EEF2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130610"> 130610 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/355?start=-3&limit=10&highlight=355"> 19p13.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/183086"> Spinocerebellar ataxia 6 </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/183086"> 183086 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601011"> CACNA1A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601011"> 601011 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/700?start=-3&limit=10&highlight=700"> 19q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617770"> ?Spinocerebellar ataxia 46 </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/617770"> 617770 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615698"> PLD3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615698"> 615698 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/978?start=-3&limit=10&highlight=978"> 19q13.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605259"> Spinocerebellar ataxia 13 </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/605259"> 605259 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176264"> KCNC3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176264"> 176264 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/1111?start=-3&limit=10&highlight=1111"> 19q13.42 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605361"> Spinocerebellar ataxia 14 </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/605361"> 605361 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176980"> PRKCG </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176980"> 176980 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/20/29?start=-3&limit=10&highlight=29"> 20p13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610245"> Spinocerebellar ataxia 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="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610245"> 610245 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/131340"> PDYN </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/131340"> 131340 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/20/32?start=-3&limit=10&highlight=32"> 20p13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613908"> Spinocerebellar ataxia 35 </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/613908"> 613908 </a>
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<a href="/entry/613900"> TGM6 </a>
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<a href="/entry/613900"> 613900 </a>
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<a href="/geneMap/20/35?start=-3&limit=10&highlight=35"> 20p13 </a>
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<a href="/entry/614153"> Spinocerebellar ataxia 36 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<a href="/entry/614153"> 614153 </a>
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<a href="/entry/614154"> NOP56 </a>
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<a href="/entry/614154"> 614154 </a>
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<a href="/entry/603516"> Spinocerebellar ataxia 10 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/603516"> 603516 </a>
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<a href="/entry/611150"> ATXN10 </a>
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<a href="/entry/611150"> 611150 </a>
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<a href="/entry/612876"> Spinocerebellar ataxia 9 </a>
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<a href="/entry/612876"> 612876 </a>
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<a href="/entry/612876"> SCA9 </a>
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<a href="/entry/612876"> 612876 </a>
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<p>A number sign (#) is used with this entry because of evidence that spinocerebellar ataxia-4 (SCA4) is caused by a heterozygous trinucleotide repeat expansion (GGCn) in the ZFHX3 gene (<a href="/entry/104155">104155</a>) on chromosome 16q22. The normal length of the trinucleotide repeat is 14 to 26 units, with the most common length being 21 repeat units, including interruptions. Disease-causing expanded repeats are greater than 40 (range from 42 to 74) units of pure GGC repeats without interruptions.</p>
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<p>Spinocerebellar ataxia-4 (SCA4) is an autosomal dominant neurologic disorder characterized by the onset of balance disturbances and gait and limb ataxia usually in the fourth decade, although earlier onset in the teens or twenties has been reported. There is evidence of genetic anticipation within families. The disorder is slowly progressive, and most patients eventually become wheelchair-bound. Additional features include hypometric or slow saccades, sensory or sensorimotor axonal peripheral neuropathy, dysarthria, and autonomic dysfunction, including orthostatic hypotension and problems with bowel or bladder control. More severely affected individuals have dysphagia and significant unintended weight loss, which may contribute to premature death. Brain imaging shows cerebellar atrophy (<a href="#8" class="mim-tip-reference" title="Wallenius, J., Kafantari, E., Jhaveri, E., Gorcenco, S., Ameur, A., Karremo, C., Dobloug, S., Karrman, K., de Koning, T., Ilinca, A., Landqvist Waldo, M., Arvidsson, A., Persson, S., Englund, E., Ehrencrona, H., Puschmann, A. &lt;strong&gt;Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.&lt;/strong&gt; Am. J. Hum. Genet. 111: 1-14, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38035881/&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;38035881&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=38035881[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/10.1016/j.ajhg.2023.11.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38035881">Wallenius et al., 2024</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38035881" 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>For a discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (<a href="/entry/164400">164400</a>).</p>
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<p><a href="#4" class="mim-tip-reference" title="Gardner, K., Alderson, K., Galster, B., Kaplan, C., Leppert, M., Ptacek, L. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. (Abstract)&lt;/strong&gt; Neurology 44: A361 only, 1994."None>Gardner et al. (1994)</a> described a large Utah kindred with a distinct form of autosomal dominant spinocerebellar ataxia. <a href="#3" class="mim-tip-reference" title="Flanigan, K., Gardner, K., Alderson, K., Galster, B., Otterud, B., Leppert, M. F., Kaplan, C., Ptacek, L. J. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1.&lt;/strong&gt; Am. J. Hum. Genet. 59: 392-399, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8755926/&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;8755926&lt;/a&gt;]" pmid="8755926">Flanigan et al. (1996)</a> presented clinical and electrophysiologic data of the family reported by <a href="#4" class="mim-tip-reference" title="Gardner, K., Alderson, K., Galster, B., Kaplan, C., Leppert, M., Ptacek, L. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. (Abstract)&lt;/strong&gt; Neurology 44: A361 only, 1994."None>Gardner et al. (1994)</a>. The phenotype consisted of ataxia with the invariant presence of a prominent axonal sensory neuropathy. Disease onset was typically in the fourth or fifth decade, but age at onset ranged from 19 to 59 years, with a median age at onset of 39 years. The earliest symptom was usually a gait disturbance, followed by difficulty with fine motor tasks and often by dysarthria. Ataxia progressed over decades, often leading to wheelchair dependence. At presentation, most patients did not complain of symptoms of neuropathy, although evidence of a length-dependent neuropathy could invariably be demonstrated on examination: all had vibratory and joint position sense loss, and 95% had at least a minimal pinprick sensation loss. All patients had absent ankle-jerk reflexes; knee-jerk reflexes were absent in 85% and complete areflexia was seen in 25%. <a href="#8" class="mim-tip-reference" title="Wallenius, J., Kafantari, E., Jhaveri, E., Gorcenco, S., Ameur, A., Karremo, C., Dobloug, S., Karrman, K., de Koning, T., Ilinca, A., Landqvist Waldo, M., Arvidsson, A., Persson, S., Englund, E., Ehrencrona, H., Puschmann, A. &lt;strong&gt;Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.&lt;/strong&gt; Am. J. Hum. Genet. 111: 1-14, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38035881/&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;38035881&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=38035881[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/10.1016/j.ajhg.2023.11.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38035881">Wallenius et al. (2024)</a> noted that the family from Utah reported by <a href="#4" class="mim-tip-reference" title="Gardner, K., Alderson, K., Galster, B., Kaplan, C., Leppert, M., Ptacek, L. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. (Abstract)&lt;/strong&gt; Neurology 44: A361 only, 1994."None>Gardner et al. (1994)</a> and <a href="#3" class="mim-tip-reference" title="Flanigan, K., Gardner, K., Alderson, K., Galster, B., Otterud, B., Leppert, M. F., Kaplan, C., Ptacek, L. J. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1.&lt;/strong&gt; Am. J. Hum. Genet. 59: 392-399, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8755926/&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;8755926&lt;/a&gt;]" pmid="8755926">Flanigan et al. (1996)</a> originated from Sweden, suggesting that they may have had SCA4 due to ZFHX3 repeat expansions as found in other SCA4 families, all Swedish, studied by them. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=38035881+8755926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
<p><a href="#5" class="mim-tip-reference" title="Hellenbroich, Y., Bubel, S., Pawlack, H., Opitz, S., Vieregge, P., Schwinger, E., Zuhlke, C. &lt;strong&gt;Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region.&lt;/strong&gt; J. Neurol. 250: 668-671, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12796826/&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;12796826&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00415-003-1052-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12796826">Hellenbroich et al. (2003)</a> reported a German family in which more than 14 individuals spanning 5 generations were affected with autosomal dominant cerebellar ataxia. The mean age at onset was 38.3 years (range 20 to 61), and there was some suggestion of genetic anticipation. All patients had cerebellar ataxia with limb dysmetria, dysarthria, and cerebellar atrophy, as well as sensory neuropathy with hypo- or areflexia, decreased sensation, and absent sural sensory nerve action potentials. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12796826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
<p><a href="#8" class="mim-tip-reference" title="Wallenius, J., Kafantari, E., Jhaveri, E., Gorcenco, S., Ameur, A., Karremo, C., Dobloug, S., Karrman, K., de Koning, T., Ilinca, A., Landqvist Waldo, M., Arvidsson, A., Persson, S., Englund, E., Ehrencrona, H., Puschmann, A. &lt;strong&gt;Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.&lt;/strong&gt; Am. J. Hum. Genet. 111: 1-14, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38035881/&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;38035881&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=38035881[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/10.1016/j.ajhg.2023.11.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38035881">Wallenius et al. (2024)</a> reported 38 individuals in 5 multigenerational families from the region of Skane in southern Sweden with autosomal dominant spinocerebellar ataxia and autonomic neuropathy. Fifteen patients were examined by the authors. Two of the families had previously been reported by <a href="#9" class="mim-tip-reference" title="Wictorin, K., Bradvik, B., Nilsson, K., Soller, M., van Westen, D., Bynke, G., Bauer, P., Schols, L., Puschmann, A. &lt;strong&gt;Autosomal dominant cerebellar ataxia with slow ocular saccades, neuropathy and orthostatism: a novel entity?&lt;/strong&gt; Parkinsonism Relat. Disord. 20: 748-754, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24787759/&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;24787759&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.parkreldis.2014.03.029&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="24787759">Wictorin et al. (2014)</a>, including 1 who had also been reported by <a href="#6" class="mim-tip-reference" title="Moller, E., Hindfelt, B., Olsson, J. E. &lt;strong&gt;HLA-determination in families with hereditary ataxia.&lt;/strong&gt; Tissue Antigens 12: 357-366, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/85351/&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;85351&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0039.1978.tb01345.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="85351">Moller et al. (1978)</a>. The patients in the study of <a href="#8" class="mim-tip-reference" title="Wallenius, J., Kafantari, E., Jhaveri, E., Gorcenco, S., Ameur, A., Karremo, C., Dobloug, S., Karrman, K., de Koning, T., Ilinca, A., Landqvist Waldo, M., Arvidsson, A., Persson, S., Englund, E., Ehrencrona, H., Puschmann, A. &lt;strong&gt;Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.&lt;/strong&gt; Am. J. Hum. Genet. 111: 1-14, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38035881/&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;38035881&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=38035881[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/10.1016/j.ajhg.2023.11.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38035881">Wallenius et al. (2024)</a> were all adults who developed gait and balance disturbances at a mean age of 37.6 years (range 15 to 60). The disorder was slowly but relentlessly progressive, and all had both gait and limb ataxia. Most patients lost the ability to stand without support and became wheelchair-bound, as well as losing handwriting ability. Affected individuals also had slow or hypometric ocular saccades, dysarthria, and distal sensory impairment with hypo- or areflexia. Electrophysiologic studies showed a sensory or sensorimotor axonal neuropathy. More variable features included torticollis, involuntary facial twitching, head tremor, involuntary leg jerks, restless legs, leg cramps, intention tremor, fasciculations, extensor plantar responses, dysmetria, dysphagia, and muscle wasting. One individual was noted to have mirror movements. Brain imaging showed cerebellar atrophy. Dysautonomia was common, mostly manifest as orthostatic hypotension and difficulties with bladder or bowel control. Several individuals with earlier onset had severe involuntary weight loss and muscle wasting due to dysphagia or swallowing difficulties. The severe weight loss in some patients was considered to have contributed to their premature deaths between 28 and 47 years of age. Patients with earlier onset had more severe additional symptomatology. Some patients died in their forties or fifties, although others survived into the late seventies; one patient was still alive at age 80. One patient died at age 28. Postmortem examination of the patient who died at 28 years of age showed mild cerebellar atrophy with neuronal loss and gliosis, a loss of pigmented cells in the substantia nigra, and moderate cell loss in the locus ceruleus. Nerve cells of the myenteric plexus in the esophagus contained p62 (SQSTM1; <a href="/entry/601530">601530</a>)-immunoreactive inclusions. Alpha-synuclein (SNCA; <a href="/entry/163890">163890</a>) immunoreactivity was seen in brainstem and medulla oblongata neurons, in the hippocampus, and in myenteric ganglion cells in the gastrointestinal tract. Lewy bodies were not observed. Of note, 2 children in family 1 (8 and 4 years of age) who did not carry the pathogenic repeat expansion in the ZFHX3 gene had a more severe and complex neurologic disorder since infancy, including delayed psychomotor development, hypotonia, delayed walking with unsteady gait, balance problems, myoclonic jerks, leg pain, joint hyperlaxity, behavioral problems, incontinence, and cerebellar atrophy on brain imaging. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=38035881+85351+24787759" 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>
<div class="mim-changed mim-change"><p><a href="#2" class="mim-tip-reference" title="Figueroa, K. P., Gross, C., Buena-Atienza, E., Paul, S., Gandelman, M., Kakar, N., Sturm, M., Casadei, N., Admard, J., Park, J., Zuhlke, C., Hellenbroich, Y., and 18 others. &lt;strong&gt;A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.&lt;/strong&gt; Nature Genet. 56: 1080-1089, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38684900/&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;38684900&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41588-024-01719-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38684900">Figueroa et al. (2024)</a> reported numerous individuals from 8 families, including the large multigenerational Utah pedigree (UTA) previously reported by <a href="#4" class="mim-tip-reference" title="Gardner, K., Alderson, K., Galster, B., Kaplan, C., Leppert, M., Ptacek, L. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. (Abstract)&lt;/strong&gt; Neurology 44: A361 only, 1994."None>Gardner et al. (1994)</a> and <a href="#3" class="mim-tip-reference" title="Flanigan, K., Gardner, K., Alderson, K., Galster, B., Otterud, B., Leppert, M. F., Kaplan, C., Ptacek, L. J. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1.&lt;/strong&gt; Am. J. Hum. Genet. 59: 392-399, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8755926/&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;8755926&lt;/a&gt;]" pmid="8755926">Flanigan et al. (1996)</a>, with SCA4 confirmed by genetic analysis. The Utah kindred could be traced back to a likely common ancestor born in southern Sweden around the start of the 19th century. The 7 newly described families were of German descent (Lubeck, Munchen, Magdeburg 1 and 2, Essen 1 and 2, and Hamburg). Haplotype analysis showed that several of the families shared a common repeat expansion haplotype. Most patients had onset of symptoms in adulthood (range 30 to 65 years), although some patients in later generations had earlier onset in the second or third decade, consistent with genetic anticipation. The presenting feature was usually gait ataxia and impaired balance, followed by dysarthria and peripheral sensorimotor neuropathy. Most had oculomotor defects, such as saccadic pursuit, saccadic intrusions, and gaze-evoked nystagmus. Additional more variable features included dysphagia, chronic cough, and autonomic dysfunction manifest as orthostatic hypotension, erectile dysfunction, and incontinence. Rare patients had exercise-induced dystonia, tongue fasciculations, tremor, myoclonic jerks, extensor plantar responses, and sleep disturbances. Brain imaging showed cerebellar atrophy, sometimes with spinal cord atrophy. Neuropathologic examination of a man who died 30 years after onset showed depletion of Purkinje cells in the cerebellum and neuronal intranuclear inclusions (NII) that were immunoreactive to ZFHX3, ubiquitin, and p62. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8755926+38684900" 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></div>
<div class="mim-changed mim-change"><p><a href="#7" class="mim-tip-reference" title="Paucar, M., Nilsson, D., Engvall, M., Laffita-Mesa, J., Soderhall, C., Skorpil, M., Halldin, C., Fazio, P., Lagerstedt-Robinson, K., Solders, G., Angeria, M., Varrone, A., Risling, M., Jiao, H., Nennesmo, I., Wedell, A., Svenningsson, P. &lt;strong&gt;Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.&lt;/strong&gt; J. Intern. Med. 296: 234-248, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38973251/&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;38973251&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/joim.13815&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="38973251">Paucar et al. (2024)</a> reported 3 large multigenerational families from southern Sweden with SCA4. The mean age at symptom onset was 56.4 years (range 20 to 60 years), and genetic anticipation was observed in all families. Common features included gait ataxia, cerebellar atrophy, and sensorimotor neuropathy with areflexia. Additional features included dysautonomia with abnormal tilt test, motor neuron involvement (muscle weakness, Babinski sign), eye movement abnormalities (slow saccades, ophthalmoplegia), and movement disorders other than ataxia, such as dystonia and myokymia. Advanced disease was characterized by severe weight loss and recurrent pneumonias sometimes requiring gastrostomy. Moderate to severe loss of myelinated fibers was seen in 2 sural nerve biopsies. Neuroimaging showed progressive atrophy in the cerebellum, brainstem, and spinal cord, and PET scan showed brain hypometabolism in several subcortical regions and the cerebellum. Postmortem neuropathologic examination of 1 patient showed a moderate to severe loss of Purkinje cells in the cerebellum and of motor neurons in the anterior horns of the spinal cord, as well as pronounced degradation of the posterior tracts. Intranuclear, mainly neuronal, inclusions positive for p62 and ubiquitin were sparse, but widespread in the brain and upper spinal cord. Occasional polyQ-positive intranuclear inclusions were present in neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38973251" 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></div>
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<div class="mim-changed mim-change"><p>The transmission pattern of SCA4 in the families reported by <a href="#8" class="mim-tip-reference" title="Wallenius, J., Kafantari, E., Jhaveri, E., Gorcenco, S., Ameur, A., Karremo, C., Dobloug, S., Karrman, K., de Koning, T., Ilinca, A., Landqvist Waldo, M., Arvidsson, A., Persson, S., Englund, E., Ehrencrona, H., Puschmann, A. &lt;strong&gt;Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.&lt;/strong&gt; Am. J. Hum. Genet. 111: 1-14, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38035881/&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;38035881&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=38035881[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/10.1016/j.ajhg.2023.11.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38035881">Wallenius et al. (2024)</a> was consistent with autosomal dominant inheritance with genetic anticipation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38035881" 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></div>
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<p>By linkage analysis of a Utah kindred with autosomal dominant SCA with sensory neuropathy, <a href="#4" class="mim-tip-reference" title="Gardner, K., Alderson, K., Galster, B., Kaplan, C., Leppert, M., Ptacek, L. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. (Abstract)&lt;/strong&gt; Neurology 44: A361 only, 1994."None>Gardner et al. (1994)</a> identified a candidate disease locus, termed SCA4, on chromosome 16q.</p><p><a href="#3" class="mim-tip-reference" title="Flanigan, K., Gardner, K., Alderson, K., Galster, B., Otterud, B., Leppert, M. F., Kaplan, C., Ptacek, L. J. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1.&lt;/strong&gt; Am. J. Hum. Genet. 59: 392-399, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8755926/&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;8755926&lt;/a&gt;]" pmid="8755926">Flanigan et al. (1996)</a> provided full information on the mapping of the SCA4 locus identified by <a href="#4" class="mim-tip-reference" title="Gardner, K., Alderson, K., Galster, B., Kaplan, C., Leppert, M., Ptacek, L. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. (Abstract)&lt;/strong&gt; Neurology 44: A361 only, 1994."None>Gardner et al. (1994)</a> to 16q22.1. The disorder was mapped in a 5-generation family with an autosomal dominant, late-onset spinocerebellar ataxia; the gene was tightly linked to the microsatellite marker D16S397 (lod = 5.93 at theta = 0.00). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8755926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By linkage analysis of a German family with autosomal dominant SCA, <a href="#5" class="mim-tip-reference" title="Hellenbroich, Y., Bubel, S., Pawlack, H., Opitz, S., Vieregge, P., Schwinger, E., Zuhlke, C. &lt;strong&gt;Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region.&lt;/strong&gt; J. Neurol. 250: 668-671, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12796826/&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;12796826&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00415-003-1052-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12796826">Hellenbroich et al. (2003)</a> identified a 3.69-cM region on chromosome 16q22 between markers D16S3019 and D16S512 (maximum 2-point lod score of 4.48 at D16S3018). Analysis of 9 CAG/CTG tracts in this region showed no evidence for a repeat expansion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12796826" 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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<div class="mim-changed mim-change"><p>In 2024, 3 different research groups (<a href="#8" class="mim-tip-reference" title="Wallenius, J., Kafantari, E., Jhaveri, E., Gorcenco, S., Ameur, A., Karremo, C., Dobloug, S., Karrman, K., de Koning, T., Ilinca, A., Landqvist Waldo, M., Arvidsson, A., Persson, S., Englund, E., Ehrencrona, H., Puschmann, A. &lt;strong&gt;Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.&lt;/strong&gt; Am. J. Hum. Genet. 111: 1-14, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38035881/&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;38035881&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=38035881[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/10.1016/j.ajhg.2023.11.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38035881">Wallenius et al., 2024</a>, <a href="#2" class="mim-tip-reference" title="Figueroa, K. P., Gross, C., Buena-Atienza, E., Paul, S., Gandelman, M., Kakar, N., Sturm, M., Casadei, N., Admard, J., Park, J., Zuhlke, C., Hellenbroich, Y., and 18 others. &lt;strong&gt;A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.&lt;/strong&gt; Nature Genet. 56: 1080-1089, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38684900/&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;38684900&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41588-024-01719-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38684900">Figueroa et al., 2024</a>, and <a href="#7" class="mim-tip-reference" title="Paucar, M., Nilsson, D., Engvall, M., Laffita-Mesa, J., Soderhall, C., Skorpil, M., Halldin, C., Fazio, P., Lagerstedt-Robinson, K., Solders, G., Angeria, M., Varrone, A., Risling, M., Jiao, H., Nennesmo, I., Wedell, A., Svenningsson, P. &lt;strong&gt;Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.&lt;/strong&gt; J. Intern. Med. 296: 234-248, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38973251/&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;38973251&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/joim.13815&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="38973251">Paucar et al., 2024</a>) independently identified a heterozygous GGC(n) trinucleotide repeat expansion in the ZFHX3 gene (<a href="/entry/104155#0003">104155.0003</a>) as the cause of spinocerebellar ataxia-4 (SCA4) that had been mapped to chromosome 16q22. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=38973251+38035881+38684900" 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></div>
<p>In 8 affected individuals from 5 Swedish families with SCA4, <a href="#8" class="mim-tip-reference" title="Wallenius, J., Kafantari, E., Jhaveri, E., Gorcenco, S., Ameur, A., Karremo, C., Dobloug, S., Karrman, K., de Koning, T., Ilinca, A., Landqvist Waldo, M., Arvidsson, A., Persson, S., Englund, E., Ehrencrona, H., Puschmann, A. &lt;strong&gt;Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.&lt;/strong&gt; Am. J. Hum. Genet. 111: 1-14, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38035881/&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;38035881&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=38035881[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/10.1016/j.ajhg.2023.11.008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38035881">Wallenius et al. (2024)</a> identified a heterozygous 3-bp (GGC) repeat expansion in the last coding exon (exon 10) of the ZFHX3 gene (<a href="/entry/104155#0003">104155.0003</a>); the GGC repeat encoded a glycine residue. All families originated from Skane, the southernmost region of Sweden, and haplotype analysis indicated a founder effect. Two of the families had previously been reported (see <a href="#6" class="mim-tip-reference" title="Moller, E., Hindfelt, B., Olsson, J. E. &lt;strong&gt;HLA-determination in families with hereditary ataxia.&lt;/strong&gt; Tissue Antigens 12: 357-366, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/85351/&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;85351&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0039.1978.tb01345.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="85351">Moller et al., 1978</a> and <a href="#9" class="mim-tip-reference" title="Wictorin, K., Bradvik, B., Nilsson, K., Soller, M., van Westen, D., Bynke, G., Bauer, P., Schols, L., Puschmann, A. &lt;strong&gt;Autosomal dominant cerebellar ataxia with slow ocular saccades, neuropathy and orthostatism: a novel entity?&lt;/strong&gt; Parkinsonism Relat. Disord. 20: 748-754, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24787759/&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;24787759&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.parkreldis.2014.03.029&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="24787759">Wictorin et al., 2014</a>). The repeat was expanded to greater than 40 repeats (range 42 to 74) in affected individuals, whereas the most common nonexpanded repeat length was reported as 21 repeats (range 14 to 26) in controls. The nonexpanded repeat in controls consisted of 20 glycine residues interrupted by a single serine. All nonexpanded alleles had interruptions within the GGC repeat; the interruptions were predominantly synonymous GGT and a nonsynonymous AGT (serine). Pathogenic expanded alleles did not contain interruptions: GGC was the only repeat unit. Genetic anticipation was observed, and there was a correlation between longer repeat expansions and earlier age at symptom onset. Long-read sequencing in a patient from family 1 who had onset at age 37 years showed 57 uninterrupted GGC repeats, whereas a patient in a later generation in family 1 who had onset at 15 years of age had 74 uninterrupted GGC repeats. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=38035881+85351+24787759" 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>
<div class="mim-changed mim-change"><p>In affected members of 8 families with SCA4, <a href="#2" class="mim-tip-reference" title="Figueroa, K. P., Gross, C., Buena-Atienza, E., Paul, S., Gandelman, M., Kakar, N., Sturm, M., Casadei, N., Admard, J., Park, J., Zuhlke, C., Hellenbroich, Y., and 18 others. &lt;strong&gt;A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.&lt;/strong&gt; Nature Genet. 56: 1080-1089, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38684900/&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;38684900&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41588-024-01719-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="38684900">Figueroa et al. (2024)</a> identified a heterozygous a GGC(n) repeat expansion in the last coding exon (exon 10) of the ZFHX3 gene (<a href="/entry/104155#0003">104155.0003</a>). The repeat, which was found by long-read genome sequencing, segregated with the disorder in the families in an autosomal dominant pattern of inheritance. The normal allele had 21 repeats, whereas the pathogenic GGC repeat was over 45 repeats (up to 61 repeats) and was translated into a polyG domain in-frame with the rest of the ZFHX3 protein as demonstrated in patient fibroblasts. There was a significant inverse correlation between age at onset and repeat expansion length. One of the families was a large multigenerational family from Utah previously reported by <a href="#4" class="mim-tip-reference" title="Gardner, K., Alderson, K., Galster, B., Kaplan, C., Leppert, M., Ptacek, L. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. (Abstract)&lt;/strong&gt; Neurology 44: A361 only, 1994."None>Gardner et al. (1994)</a> and <a href="#3" class="mim-tip-reference" title="Flanigan, K., Gardner, K., Alderson, K., Galster, B., Otterud, B., Leppert, M. F., Kaplan, C., Ptacek, L. J. &lt;strong&gt;Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1.&lt;/strong&gt; Am. J. Hum. Genet. 59: 392-399, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8755926/&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;8755926&lt;/a&gt;]" pmid="8755926">Flanigan et al. (1996)</a> who could be traced to a common ancestor in southern Sweden around the start of the 19th century. The 7 other families were from Germany (Lubeck, Munchen, Magdeburg 1 and 2, Essen 1 and 2, and Hamburg). Haplotype analysis showed that several of the families shared a common repeat expansion haplotype. Fibroblast samples from 4 SCA4 patients in the Utah family showed evidence of abnormal autophagy compared to controls. Wildtype ATXN2 was upregulated in all patient samples. Induced pluripotent stem cells (iPSCs) generated from one SCA4 patient from the Utah family with 21/53 repeats contained increased polyG-expanded ZFHX3 protein levels, but became rapidly apoptotic upon induction of differentiation to neurons, whereas control iPSCs easily differentiated into neurons under similar conditions. Neuropathologic examination of 1 patient detected neuronal intranuclear inclusions (NII) in the cerebellum that were immunoreactive to ZFHX3, ubiquitin, and p62 (SQSTM1; <a href="/entry/601530">601530</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8755926+38684900" 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></div>
<div class="mim-changed mim-change"><p>Using a combination of methods, including long-read sequencing, <a href="#7" class="mim-tip-reference" title="Paucar, M., Nilsson, D., Engvall, M., Laffita-Mesa, J., Soderhall, C., Skorpil, M., Halldin, C., Fazio, P., Lagerstedt-Robinson, K., Solders, G., Angeria, M., Varrone, A., Risling, M., Jiao, H., Nennesmo, I., Wedell, A., Svenningsson, P. &lt;strong&gt;Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.&lt;/strong&gt; J. Intern. Med. 296: 234-248, 2024.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/38973251/&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;38973251&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/joim.13815&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="38973251">Paucar et al. (2024)</a> identified a heterozygous GGC(n) repeat expansion in the coding region of the ZFHX3 gene (<a href="/entry/104155#0003">104155.0003</a>) in affected member of 3 multigenerational Swedish families with SCA4. The pathogenic repeat ranged from 46 to 64 copies. The majority of normal alleles contained 21 copies, with a maximum of 26 copies. Functional studies of the variant were not performed, but neuropathologic studies of 4 patients showed intranuclear inclusions positive for ubiquitin and p62. Polyglycine-positive inclusions were found in neurons in 1 patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38973251" 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></div>
<p><strong><em>Exclusion Studies</em></strong>
</p>
<p><a href="#1" class="mim-tip-reference" title="Edener, U., Bernard, V., Hellenbroich, Y., Gillessen-Kaesbach, G., Zuhlke, C. &lt;strong&gt;Two dominantly inherited ataxias linked to chromosome 16q22.1: SCA4 and SCA31 are not allelic.&lt;/strong&gt; J. Neurol. 258: 1223-1227, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21267591/&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;21267591&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00415-011-5905-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21267591">Edener et al. (2011)</a> excluded a pathogenic pentanucleotide repeat in the BEAN gene, which causes SCA31, as a cause of SCA4 in the family reported by <a href="#5" class="mim-tip-reference" title="Hellenbroich, Y., Bubel, S., Pawlack, H., Opitz, S., Vieregge, P., Schwinger, E., Zuhlke, C. &lt;strong&gt;Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region.&lt;/strong&gt; J. Neurol. 250: 668-671, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12796826/&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;12796826&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00415-003-1052-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12796826">Hellenbroich et al. (2003)</a>, indicating that SCA4 and SCA31 are not allelic disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21267591+12796826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
<a id="Edener2011" class="mim-anchor"></a>
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<p class="mim-text-font">
Edener, U., Bernard, V., Hellenbroich, Y., Gillessen-Kaesbach, G., Zuhlke, C.
<strong>Two dominantly inherited ataxias linked to chromosome 16q22.1: SCA4 and SCA31 are not allelic.</strong>
J. Neurol. 258: 1223-1227, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21267591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21267591</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21267591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s00415-011-5905-4" target="_blank">Full Text</a>]
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<a id="Figueroa2024" class="mim-anchor"></a>
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Figueroa, K. P., Gross, C., Buena-Atienza, E., Paul, S., Gandelman, M., Kakar, N., Sturm, M., Casadei, N., Admard, J., Park, J., Zuhlke, C., Hellenbroich, Y., and 18 others.
<strong>A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.</strong>
Nature Genet. 56: 1080-1089, 2024.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38684900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38684900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38684900" 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/s41588-024-01719-5" target="_blank">Full Text</a>]
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<a id="Flanigan1996" class="mim-anchor"></a>
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Flanigan, K., Gardner, K., Alderson, K., Galster, B., Otterud, B., Leppert, M. F., Kaplan, C., Ptacek, L. J.
<strong>Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1.</strong>
Am. J. Hum. Genet. 59: 392-399, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8755926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8755926</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8755926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Gardner1994" class="mim-anchor"></a>
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<p class="mim-text-font">
Gardner, K., Alderson, K., Galster, B., Kaplan, C., Leppert, M., Ptacek, L.
<strong>Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. (Abstract)</strong>
Neurology 44: A361 only, 1994.
</p>
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<a id="5" class="mim-anchor"></a>
<a id="Hellenbroich2003" class="mim-anchor"></a>
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<p class="mim-text-font">
Hellenbroich, Y., Bubel, S., Pawlack, H., Opitz, S., Vieregge, P., Schwinger, E., Zuhlke, C.
<strong>Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region.</strong>
J. Neurol. 250: 668-671, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12796826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12796826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12796826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s00415-003-1052-x" target="_blank">Full Text</a>]
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<a id="Moller1978" class="mim-anchor"></a>
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Moller, E., Hindfelt, B., Olsson, J. E.
<strong>HLA-determination in families with hereditary ataxia.</strong>
Tissue Antigens 12: 357-366, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/85351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">85351</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=85351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0039.1978.tb01345.x" target="_blank">Full Text</a>]
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<a id="Paucar2024" class="mim-anchor"></a>
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Paucar, M., Nilsson, D., Engvall, M., Laffita-Mesa, J., Soderhall, C., Skorpil, M., Halldin, C., Fazio, P., Lagerstedt-Robinson, K., Solders, G., Angeria, M., Varrone, A., Risling, M., Jiao, H., Nennesmo, I., Wedell, A., Svenningsson, P.
<strong>Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.</strong>
J. Intern. Med. 296: 234-248, 2024.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38973251</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38973251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/joim.13815" target="_blank">Full Text</a>]
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<a id="Wallenius2024" class="mim-anchor"></a>
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Wallenius, J., Kafantari, E., Jhaveri, E., Gorcenco, S., Ameur, A., Karremo, C., Dobloug, S., Karrman, K., de Koning, T., Ilinca, A., Landqvist Waldo, M., Arvidsson, A., Persson, S., Englund, E., Ehrencrona, H., Puschmann, A.
<strong>Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.</strong>
Am. J. Hum. Genet. 111: 1-14, 2024.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38035881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38035881</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=38035881[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=38035881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ajhg.2023.11.008" target="_blank">Full Text</a>]
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<a id="Wictorin2014" class="mim-anchor"></a>
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Wictorin, K., Bradvik, B., Nilsson, K., Soller, M., van Westen, D., Bynke, G., Bauer, P., Schols, L., Puschmann, A.
<strong>Autosomal dominant cerebellar ataxia with slow ocular saccades, neuropathy and orthostatism: a novel entity?</strong>
Parkinsonism Relat. Disord. 20: 748-754, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24787759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24787759</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24787759" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.parkreldis.2014.03.029" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 12/13/2024
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Cassandra L. Kniffin - updated : 12/11/2023<br>Cassandra L. Kniffin - updated : 9/20/2011<br>Cassandra L. Kniffin - updated : 11/4/2005<br>Cassandra L. Kniffin - updated : 8/9/2005<br>Victor A. McKusick - updated : 3/26/2003
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Victor A. McKusick : 12/7/1994
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carol : 02/07/2025
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alopez : 12/13/2024<br>ckniffin : 12/13/2024<br>alopez : 12/15/2023<br>ckniffin : 12/11/2023<br>carol : 09/22/2011<br>ckniffin : 9/20/2011<br>carol : 3/29/2011<br>terry : 12/22/2010<br>wwang : 2/5/2010<br>wwang : 11/14/2005<br>ckniffin : 11/4/2005<br>wwang : 9/22/2005<br>ckniffin : 9/21/2005<br>ckniffin : 8/9/2005<br>joanna : 3/17/2004<br>carol : 3/26/2003<br>carol : 3/26/2003<br>terry : 3/26/2003<br>alopez : 9/29/2000<br>mark : 9/11/1996<br>terry : 9/3/1996<br>mimadm : 9/23/1995<br>carol : 12/7/1994
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<strong>#</strong> 600223
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<span class="mim-font">
SPINOCEREBELLAR ATAXIA 4; SCA4
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<em>Alternative titles; symbols</em>
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SPINOCEREBELLAR ATAXIA, AUTOSOMAL DOMINANT, WITH SENSORY AXONAL NEUROPATHY
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<strong>SNOMEDCT:</strong> 715755008; &nbsp;
<strong>ORPHA:</strong> 98765; &nbsp;
<strong>DO:</strong> 0050957; &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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16q22.2-q22.3
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Spinocerebellar ataxia 4
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600223
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Autosomal dominant
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3
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ZFHX3
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104155
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that spinocerebellar ataxia-4 (SCA4) is caused by a heterozygous trinucleotide repeat expansion (GGCn) in the ZFHX3 gene (104155) on chromosome 16q22. The normal length of the trinucleotide repeat is 14 to 26 units, with the most common length being 21 repeat units, including interruptions. Disease-causing expanded repeats are greater than 40 (range from 42 to 74) units of pure GGC repeats without interruptions.</p>
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<strong>Description</strong>
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<p>Spinocerebellar ataxia-4 (SCA4) is an autosomal dominant neurologic disorder characterized by the onset of balance disturbances and gait and limb ataxia usually in the fourth decade, although earlier onset in the teens or twenties has been reported. There is evidence of genetic anticipation within families. The disorder is slowly progressive, and most patients eventually become wheelchair-bound. Additional features include hypometric or slow saccades, sensory or sensorimotor axonal peripheral neuropathy, dysarthria, and autonomic dysfunction, including orthostatic hypotension and problems with bowel or bladder control. More severely affected individuals have dysphagia and significant unintended weight loss, which may contribute to premature death. Brain imaging shows cerebellar atrophy (Wallenius et al., 2024). </p><p>For a discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).</p>
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<strong>Clinical Features</strong>
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<p>Gardner et al. (1994) described a large Utah kindred with a distinct form of autosomal dominant spinocerebellar ataxia. Flanigan et al. (1996) presented clinical and electrophysiologic data of the family reported by Gardner et al. (1994). The phenotype consisted of ataxia with the invariant presence of a prominent axonal sensory neuropathy. Disease onset was typically in the fourth or fifth decade, but age at onset ranged from 19 to 59 years, with a median age at onset of 39 years. The earliest symptom was usually a gait disturbance, followed by difficulty with fine motor tasks and often by dysarthria. Ataxia progressed over decades, often leading to wheelchair dependence. At presentation, most patients did not complain of symptoms of neuropathy, although evidence of a length-dependent neuropathy could invariably be demonstrated on examination: all had vibratory and joint position sense loss, and 95% had at least a minimal pinprick sensation loss. All patients had absent ankle-jerk reflexes; knee-jerk reflexes were absent in 85% and complete areflexia was seen in 25%. Wallenius et al. (2024) noted that the family from Utah reported by Gardner et al. (1994) and Flanigan et al. (1996) originated from Sweden, suggesting that they may have had SCA4 due to ZFHX3 repeat expansions as found in other SCA4 families, all Swedish, studied by them. </p><p>Hellenbroich et al. (2003) reported a German family in which more than 14 individuals spanning 5 generations were affected with autosomal dominant cerebellar ataxia. The mean age at onset was 38.3 years (range 20 to 61), and there was some suggestion of genetic anticipation. All patients had cerebellar ataxia with limb dysmetria, dysarthria, and cerebellar atrophy, as well as sensory neuropathy with hypo- or areflexia, decreased sensation, and absent sural sensory nerve action potentials. </p><p>Wallenius et al. (2024) reported 38 individuals in 5 multigenerational families from the region of Skane in southern Sweden with autosomal dominant spinocerebellar ataxia and autonomic neuropathy. Fifteen patients were examined by the authors. Two of the families had previously been reported by Wictorin et al. (2014), including 1 who had also been reported by Moller et al. (1978). The patients in the study of Wallenius et al. (2024) were all adults who developed gait and balance disturbances at a mean age of 37.6 years (range 15 to 60). The disorder was slowly but relentlessly progressive, and all had both gait and limb ataxia. Most patients lost the ability to stand without support and became wheelchair-bound, as well as losing handwriting ability. Affected individuals also had slow or hypometric ocular saccades, dysarthria, and distal sensory impairment with hypo- or areflexia. Electrophysiologic studies showed a sensory or sensorimotor axonal neuropathy. More variable features included torticollis, involuntary facial twitching, head tremor, involuntary leg jerks, restless legs, leg cramps, intention tremor, fasciculations, extensor plantar responses, dysmetria, dysphagia, and muscle wasting. One individual was noted to have mirror movements. Brain imaging showed cerebellar atrophy. Dysautonomia was common, mostly manifest as orthostatic hypotension and difficulties with bladder or bowel control. Several individuals with earlier onset had severe involuntary weight loss and muscle wasting due to dysphagia or swallowing difficulties. The severe weight loss in some patients was considered to have contributed to their premature deaths between 28 and 47 years of age. Patients with earlier onset had more severe additional symptomatology. Some patients died in their forties or fifties, although others survived into the late seventies; one patient was still alive at age 80. One patient died at age 28. Postmortem examination of the patient who died at 28 years of age showed mild cerebellar atrophy with neuronal loss and gliosis, a loss of pigmented cells in the substantia nigra, and moderate cell loss in the locus ceruleus. Nerve cells of the myenteric plexus in the esophagus contained p62 (SQSTM1; 601530)-immunoreactive inclusions. Alpha-synuclein (SNCA; 163890) immunoreactivity was seen in brainstem and medulla oblongata neurons, in the hippocampus, and in myenteric ganglion cells in the gastrointestinal tract. Lewy bodies were not observed. Of note, 2 children in family 1 (8 and 4 years of age) who did not carry the pathogenic repeat expansion in the ZFHX3 gene had a more severe and complex neurologic disorder since infancy, including delayed psychomotor development, hypotonia, delayed walking with unsteady gait, balance problems, myoclonic jerks, leg pain, joint hyperlaxity, behavioral problems, incontinence, and cerebellar atrophy on brain imaging. </p><p>Figueroa et al. (2024) reported numerous individuals from 8 families, including the large multigenerational Utah pedigree (UTA) previously reported by Gardner et al. (1994) and Flanigan et al. (1996), with SCA4 confirmed by genetic analysis. The Utah kindred could be traced back to a likely common ancestor born in southern Sweden around the start of the 19th century. The 7 newly described families were of German descent (Lubeck, Munchen, Magdeburg 1 and 2, Essen 1 and 2, and Hamburg). Haplotype analysis showed that several of the families shared a common repeat expansion haplotype. Most patients had onset of symptoms in adulthood (range 30 to 65 years), although some patients in later generations had earlier onset in the second or third decade, consistent with genetic anticipation. The presenting feature was usually gait ataxia and impaired balance, followed by dysarthria and peripheral sensorimotor neuropathy. Most had oculomotor defects, such as saccadic pursuit, saccadic intrusions, and gaze-evoked nystagmus. Additional more variable features included dysphagia, chronic cough, and autonomic dysfunction manifest as orthostatic hypotension, erectile dysfunction, and incontinence. Rare patients had exercise-induced dystonia, tongue fasciculations, tremor, myoclonic jerks, extensor plantar responses, and sleep disturbances. Brain imaging showed cerebellar atrophy, sometimes with spinal cord atrophy. Neuropathologic examination of a man who died 30 years after onset showed depletion of Purkinje cells in the cerebellum and neuronal intranuclear inclusions (NII) that were immunoreactive to ZFHX3, ubiquitin, and p62. </p><p>Paucar et al. (2024) reported 3 large multigenerational families from southern Sweden with SCA4. The mean age at symptom onset was 56.4 years (range 20 to 60 years), and genetic anticipation was observed in all families. Common features included gait ataxia, cerebellar atrophy, and sensorimotor neuropathy with areflexia. Additional features included dysautonomia with abnormal tilt test, motor neuron involvement (muscle weakness, Babinski sign), eye movement abnormalities (slow saccades, ophthalmoplegia), and movement disorders other than ataxia, such as dystonia and myokymia. Advanced disease was characterized by severe weight loss and recurrent pneumonias sometimes requiring gastrostomy. Moderate to severe loss of myelinated fibers was seen in 2 sural nerve biopsies. Neuroimaging showed progressive atrophy in the cerebellum, brainstem, and spinal cord, and PET scan showed brain hypometabolism in several subcortical regions and the cerebellum. Postmortem neuropathologic examination of 1 patient showed a moderate to severe loss of Purkinje cells in the cerebellum and of motor neurons in the anterior horns of the spinal cord, as well as pronounced degradation of the posterior tracts. Intranuclear, mainly neuronal, inclusions positive for p62 and ubiquitin were sparse, but widespread in the brain and upper spinal cord. Occasional polyQ-positive intranuclear inclusions were present in neurons. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of SCA4 in the families reported by Wallenius et al. (2024) was consistent with autosomal dominant inheritance with genetic anticipation. </p>
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<strong>Mapping</strong>
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<p>By linkage analysis of a Utah kindred with autosomal dominant SCA with sensory neuropathy, Gardner et al. (1994) identified a candidate disease locus, termed SCA4, on chromosome 16q.</p><p>Flanigan et al. (1996) provided full information on the mapping of the SCA4 locus identified by Gardner et al. (1994) to 16q22.1. The disorder was mapped in a 5-generation family with an autosomal dominant, late-onset spinocerebellar ataxia; the gene was tightly linked to the microsatellite marker D16S397 (lod = 5.93 at theta = 0.00). </p><p>By linkage analysis of a German family with autosomal dominant SCA, Hellenbroich et al. (2003) identified a 3.69-cM region on chromosome 16q22 between markers D16S3019 and D16S512 (maximum 2-point lod score of 4.48 at D16S3018). Analysis of 9 CAG/CTG tracts in this region showed no evidence for a repeat expansion. </p>
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<strong>Molecular Genetics</strong>
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<p>In 2024, 3 different research groups (Wallenius et al., 2024, Figueroa et al., 2024, and Paucar et al., 2024) independently identified a heterozygous GGC(n) trinucleotide repeat expansion in the ZFHX3 gene (104155.0003) as the cause of spinocerebellar ataxia-4 (SCA4) that had been mapped to chromosome 16q22. </p><p>In 8 affected individuals from 5 Swedish families with SCA4, Wallenius et al. (2024) identified a heterozygous 3-bp (GGC) repeat expansion in the last coding exon (exon 10) of the ZFHX3 gene (104155.0003); the GGC repeat encoded a glycine residue. All families originated from Skane, the southernmost region of Sweden, and haplotype analysis indicated a founder effect. Two of the families had previously been reported (see Moller et al., 1978 and Wictorin et al., 2014). The repeat was expanded to greater than 40 repeats (range 42 to 74) in affected individuals, whereas the most common nonexpanded repeat length was reported as 21 repeats (range 14 to 26) in controls. The nonexpanded repeat in controls consisted of 20 glycine residues interrupted by a single serine. All nonexpanded alleles had interruptions within the GGC repeat; the interruptions were predominantly synonymous GGT and a nonsynonymous AGT (serine). Pathogenic expanded alleles did not contain interruptions: GGC was the only repeat unit. Genetic anticipation was observed, and there was a correlation between longer repeat expansions and earlier age at symptom onset. Long-read sequencing in a patient from family 1 who had onset at age 37 years showed 57 uninterrupted GGC repeats, whereas a patient in a later generation in family 1 who had onset at 15 years of age had 74 uninterrupted GGC repeats. Functional studies of the variant and studies of patient cells were not performed. </p><p>In affected members of 8 families with SCA4, Figueroa et al. (2024) identified a heterozygous a GGC(n) repeat expansion in the last coding exon (exon 10) of the ZFHX3 gene (104155.0003). The repeat, which was found by long-read genome sequencing, segregated with the disorder in the families in an autosomal dominant pattern of inheritance. The normal allele had 21 repeats, whereas the pathogenic GGC repeat was over 45 repeats (up to 61 repeats) and was translated into a polyG domain in-frame with the rest of the ZFHX3 protein as demonstrated in patient fibroblasts. There was a significant inverse correlation between age at onset and repeat expansion length. One of the families was a large multigenerational family from Utah previously reported by Gardner et al. (1994) and Flanigan et al. (1996) who could be traced to a common ancestor in southern Sweden around the start of the 19th century. The 7 other families were from Germany (Lubeck, Munchen, Magdeburg 1 and 2, Essen 1 and 2, and Hamburg). Haplotype analysis showed that several of the families shared a common repeat expansion haplotype. Fibroblast samples from 4 SCA4 patients in the Utah family showed evidence of abnormal autophagy compared to controls. Wildtype ATXN2 was upregulated in all patient samples. Induced pluripotent stem cells (iPSCs) generated from one SCA4 patient from the Utah family with 21/53 repeats contained increased polyG-expanded ZFHX3 protein levels, but became rapidly apoptotic upon induction of differentiation to neurons, whereas control iPSCs easily differentiated into neurons under similar conditions. Neuropathologic examination of 1 patient detected neuronal intranuclear inclusions (NII) in the cerebellum that were immunoreactive to ZFHX3, ubiquitin, and p62 (SQSTM1; 601530). </p><p>Using a combination of methods, including long-read sequencing, Paucar et al. (2024) identified a heterozygous GGC(n) repeat expansion in the coding region of the ZFHX3 gene (104155.0003) in affected member of 3 multigenerational Swedish families with SCA4. The pathogenic repeat ranged from 46 to 64 copies. The majority of normal alleles contained 21 copies, with a maximum of 26 copies. Functional studies of the variant were not performed, but neuropathologic studies of 4 patients showed intranuclear inclusions positive for ubiquitin and p62. Polyglycine-positive inclusions were found in neurons in 1 patient. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
Edener et al. (2011) excluded a pathogenic pentanucleotide repeat in the BEAN gene, which causes SCA31, as a cause of SCA4 in the family reported by Hellenbroich et al. (2003), indicating that SCA4 and SCA31 are not allelic disorders. </p>
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<strong>REFERENCES</strong>
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Edener, U., Bernard, V., Hellenbroich, Y., Gillessen-Kaesbach, G., Zuhlke, C.
<strong>Two dominantly inherited ataxias linked to chromosome 16q22.1: SCA4 and SCA31 are not allelic.</strong>
J. Neurol. 258: 1223-1227, 2011.
[PubMed: 21267591]
[Full Text: https://doi.org/10.1007/s00415-011-5905-4]
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Figueroa, K. P., Gross, C., Buena-Atienza, E., Paul, S., Gandelman, M., Kakar, N., Sturm, M., Casadei, N., Admard, J., Park, J., Zuhlke, C., Hellenbroich, Y., and 18 others.
<strong>A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.</strong>
Nature Genet. 56: 1080-1089, 2024.
[PubMed: 38684900]
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Flanigan, K., Gardner, K., Alderson, K., Galster, B., Otterud, B., Leppert, M. F., Kaplan, C., Ptacek, L. J.
<strong>Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1.</strong>
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Gardner, K., Alderson, K., Galster, B., Kaplan, C., Leppert, M., Ptacek, L.
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Hellenbroich, Y., Bubel, S., Pawlack, H., Opitz, S., Vieregge, P., Schwinger, E., Zuhlke, C.
<strong>Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region.</strong>
J. Neurol. 250: 668-671, 2003.
[PubMed: 12796826]
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Moller, E., Hindfelt, B., Olsson, J. E.
<strong>HLA-determination in families with hereditary ataxia.</strong>
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<strong>Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.</strong>
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<strong>Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.</strong>
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