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Entry
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- #183086 - SPINOCEREBELLAR ATAXIA 6; SCA6
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- OMIM
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<p>
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<span class="h4">#183086</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/183086"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS164400"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#otherFeatures">Other Features</a>
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<a href="#mapping">Mapping</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#heterogeneity">Heterogeneity</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</a>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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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="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=13775&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="#mimGeneReviewsFold" id="mimGeneReviewsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling."><span id="mimGeneReviewsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Gene Reviews</div>
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<div id="mimGeneReviewsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK1138/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Hereditary Ataxia Overview</a></div><div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK1140/" title="Spinocerebellar Ataxia Type 6" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Spinocerebellar Ataxia Typ…</a></div>
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</div>
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<div><a href="https://www.diseaseinfosearch.org/x/6767" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/spinocerebellar-ataxia-type-6" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=183086[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98758" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0050956" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/183086" 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>
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<div><a href="https://omia.org/OMIA001270/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0050956" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 715752006<br />
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<strong>ORPHA:</strong> 98758<br />
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<strong>DO:</strong> 0050956<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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183086
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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SPINOCEREBELLAR ATAXIA 6; SCA6
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</h3>
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</div>
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<div>
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<br />
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
|
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<td>
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<span class="mim-font">
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<a href="/geneMap/19/355?start=-3&limit=10&highlight=355">
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19p13.13
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</a>
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</span>
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Spinocerebellar ataxia 6
|
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|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/183086"> 183086 </a>
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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|
|
</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>
|
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<td>
|
|
<span class="mim-font">
|
|
CACNA1A
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601011"> 601011 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
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</tbody>
|
|
</table>
|
|
</div>
|
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</div>
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<div>
|
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|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/183086" 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>
|
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|
|
<div class="btn-group">
|
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|
|
<a href="/phenotypicSeries/PS164400" class="btn btn-info" role="button"> Phenotypic Series </a>
|
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|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
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<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/183086" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/183086" 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>
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|
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<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
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|
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<div>
|
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<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>
|
|
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|
|
|
|
|
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|
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|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- 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 /> -
|
|
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 /> -
|
|
Abnormal vestibuloocular reflex (VOR) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866764&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866764</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007670" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007670</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
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|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<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 <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
|
|
Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
|
|
Dysphagia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/288939007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">288939007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40739000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40739000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/787.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span><br /> -
|
|
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 /> -
|
|
Hemiplegic migraine in some patients <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866762&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866762</a>]</span><br /> -
|
|
Selective loss of cerebellar Purkinje cells <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277660&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277660</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 neuropathy (not a prominent feature) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866763&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866763</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95662005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95662005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/789588003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">789588003</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000763" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000763</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
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|
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|
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|
|
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|
|
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|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Age of onset 20-65 years<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 /> -
|
|
Normal alleles have 4 to 18 repeats<br /> -
|
|
Pathogenic alleles have 19 to 33 repeats<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">
|
|
|
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- Caused by expanded CAG trinucleotide repeats in the alpha-1A calcium channel subunit gene (CACNA1A, <a href="/entry/601011#0007">601011.0007</a>)<br /> -
|
|
Caused by mutation in the alpha-1A calcium channel subunit gene (CACNA1A, <a href="/entry/601011#0002">601011.0002</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small">
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<div class="row">
|
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
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<h5>
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|
Spinocerebellar ataxia
|
|
- <a href="/phenotypicSeries/PS164400">PS164400</a>
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- 49 Entries
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</h5>
|
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</div>
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</div>
|
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|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<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">
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<strong>Location</strong>
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</th>
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|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
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|
<strong>Phenotype</strong>
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</th>
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|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<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/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/3/17?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/3/436?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>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/620158"> 620158 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/602367"> NPTX1 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/602367"> 602367 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/18/63?start=-3&limit=10&highlight=63"> 18p11.21 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/610246"> Spinocerebellar ataxia 28 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/610246"> 610246 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/604581"> AFG3L2 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/604581"> 604581 </a>
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</span>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/19/123?start=-3&limit=10&highlight=123"> 19p13.3 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/609306"> ?Spinocerebellar ataxia 26 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/609306"> 609306 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/130610"> EEF2 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/130610"> 130610 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/19/355?start=-3&limit=10&highlight=355"> 19p13.13 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/183086"> Spinocerebellar ataxia 6 </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/183086"> 183086 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/601011"> CACNA1A </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/601011"> 601011 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/19/700?start=-3&limit=10&highlight=700"> 19q13.2 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/617770"> ?Spinocerebellar ataxia 46 </a>
|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
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|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
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|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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|
</span>
|
|
</td>
|
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<td>
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<span class="mim-font">
|
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<a href="/entry/617770"> 617770 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615698"> PLD3 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615698"> 615698 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
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<a href="/geneMap/19/978?start=-3&limit=10&highlight=978"> 19q13.33 </a>
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|
</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>
|
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</span>
|
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</td>
|
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</tr>
|
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|
<tr>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<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>
|
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</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>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613900"> TGM6 </a>
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
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<a href="/entry/613900"> 613900 </a>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
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<span class="mim-font">
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<a href="/geneMap/20/35?start=-3&limit=10&highlight=35"> 20p13 </a>
|
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|
|
</span>
|
|
</td>
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<td>
|
|
<span class="mim-font">
|
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<a href="/entry/614153"> Spinocerebellar ataxia 36 </a>
|
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</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>
|
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|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
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<a href="/entry/614153"> 614153 </a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/614154"> NOP56 </a>
|
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</span>
|
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/614154"> 614154 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/22/380?start=-3&limit=10&highlight=380"> 22q13.31 </a>
|
|
|
|
</span>
|
|
</td>
|
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<td>
|
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<span class="mim-font">
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<a href="/entry/603516"> Spinocerebellar ataxia 10 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
|
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/603516"> 603516 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/611150"> ATXN10 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/611150"> 611150 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Not Mapped
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/612876"> Spinocerebellar ataxia 9 </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/612876"> 612876 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/612876"> SCA9 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<a href="/entry/612876"> 612876 </a>
|
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</span>
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</td>
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</tbody>
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</table>
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<div class="text-right small">
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</h4>
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<p>A number sign (#) is used with this entry because spinocerebellar ataxia-6 (SCA6) is caused by heterozygous mutation in the CACNA1A gene (<a href="/entry/601011">601011</a>) on chromosome 19p13.</p><p>The most common mutation is an expanded CAG(n) repeat in exon 47 of the CACNA1A gene (<a href="/entry/601011#0007">601011.0007</a>). Normal alleles contain 4 to 18 repeats, whereas pathogenic alleles contain 19 to 33 repeats (<a href="#15" class="mim-tip-reference" title="Li, L., Saegusa, H., Tanabe, T. <strong>Deficit of heat shock transcription factor 1-heat shock 70 kDa protein 1A axis determines the cell death vulnerability in a model of spinocerebellar ataxia type 6.</strong> Genes Cells 14: 1253-1269, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19817876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19817876</a>] [<a href="https://doi.org/10.1111/j.1365-2443.2009.01348.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19817876">Li et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19817876" 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 general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (<a href="/entry/164400">164400</a>).</p>
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</span>
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<div>
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<p><a href="#28" class="mim-tip-reference" title="Subramony, S. H., Fratkin, J. D., Manyam, B. V., Currier, R. D. <strong>Dominantly inherited cerebello-olivary atrophy is not due to a mutation at the spinocerebellar ataxia-I, Machado-Joseph disease, or dentato-rubro-pallido-luysian atrophy locus.</strong> Movement Disorders 11: 174-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8684388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8684388</a>] [<a href="https://doi.org/10.1002/mds.870110210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8684388">Subramony et al. (1996)</a> described a family segregating late-onset progressive cerebellar ataxia with onset of gait difficulties at age 50. There was no pontine atrophy at autopsy nor was there evidence of hypogonadism. The segregation appeared to be autosomal dominant with multiple instances of male-to-male transmission. Direct DNA analysis excluded expansions at the SCA1 (<a href="/entry/164400">164400</a>), Machado-Joseph (<a href="/entry/607047">607047</a>), and DRPLA (<a href="/entry/125370">125370</a>) loci. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8684388" 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="#42" class="mim-tip-reference" title="Zhuchenko, O., Bailey, J., Bonnen, P., Ashizawa, T., Stockton, D. W., Amos, C., Dobyns, W. B., Subramony, S. H., Zoghbi, H. Y., Lee, C. C. <strong>Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha(1A)-voltage-dependent calcium channel.</strong> Nature Genet. 15: 62-69, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988170</a>] [<a href="https://doi.org/10.1038/ng0197-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8988170">Zhuchenko et al. (1997)</a> reported 8 unrelated families who showed a very similar clinical picture consisting predominantly of mild but slowly progressive cerebellar ataxia of the limbs and gait, dysarthria, nystagmus, and mild vibratory and proprioceptive sensory loss. The disease is insidious and most patients do not realize they are affected initially but do describe a sense of momentary imbalance and 'wooziness' when they make a quick turn or a rapid movement. Typically, it is years after this initial sensation when the patients realize they have developed balance and coordination difficulties. The disease usually progresses over 20 to 30 years, leading to impairment of gait and causing the patient to become wheelchair-bound. In a few older patients, choking has been observed, suggesting involvement of the brainstem. The disease was the cause of death in several members of 2 kindreds. Magnetic resonance imaging (MRI) of the brain in affected individuals demonstrated isolated cerebellar atrophy. By genotype survey, <a href="#42" class="mim-tip-reference" title="Zhuchenko, O., Bailey, J., Bonnen, P., Ashizawa, T., Stockton, D. W., Amos, C., Dobyns, W. B., Subramony, S. H., Zoghbi, H. Y., Lee, C. C. <strong>Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha(1A)-voltage-dependent calcium channel.</strong> Nature Genet. 15: 62-69, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988170</a>] [<a href="https://doi.org/10.1038/ng0197-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8988170">Zhuchenko et al. (1997)</a> found a CAG repeat expansion in the CACNA1A gene (see MOLECULAR GENETICS). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8988170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The clinical and genetic features of 38 genetically confirmed cases of SCA6 from 8 families were described by <a href="#11" class="mim-tip-reference" title="Ishikawa, K., Tanaka, H., Saito, M., Ohkoshi, N., Fujita, T., Yoshizawa, K., Ikeuchi, T., Watanabe, M., Hayashi, A., Takiyama, Y., Nishizawa, M., Nakano, I., Matsubayashi, K., Miwa, M., Shoji, S., Kanazawa, I., Tsuji, S., Mizusawa, H. <strong>Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1.</strong> Am. J. Hum. Genet. 61: 336-346, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9311738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9311738</a>] [<a href="https://doi.org/10.1086/514867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9311738">Ishikawa et al. (1997)</a>. Gait ataxia was invariably the initial symptom and was the chief symptom throughout the clinical course. Other symptoms were cerebellar speech, limb ataxia, decreased muscle tonus, and horizontal gaze nystagmus. Tendon reflexes were normal or slightly increased. Extracerebellar symptoms, such as pyramidal or extrapyramidal tract signs, ophthalmoparesis, or decreased sensation, were not seen. None of the patients complained of migraine. Magnetic resonance imaging demonstrated atrophy restricted to the cerebellum. The age at onset ranged from 20 to 66 years, and the average age at onset was 45 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9311738" 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="#9" class="mim-tip-reference" title="Gomez, C. M., Thompson, R. M., Gammack, J. T., Perlman, S. L., Dobyns, W. B., Truwit, C. L., Zee, D. S., Clark, H. B., Anderson, J. H. <strong>Spinocerebellar ataxia type 6: gaze-evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset.</strong> Ann. Neurol. 42: 933-950, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9403487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9403487</a>] [<a href="https://doi.org/10.1002/ana.410420616" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9403487">Gomez et al. (1997)</a> described clinical, genetic, neuroimaging, neuropathologic, and quantitative oculomotor studies in 4 kindreds with genotypically confirmed SCA6. The age of onset of ataxia ranged from 24 to 63 years among affected individuals. Radiographically and pathologically, there was selective atrophy of the cerebellum and extensive loss of Purkinje cells in the cerebellar cortex. In addition, clinical and quantitative measurement of extraocular movements demonstrated a characteristic pattern of oculomotor and vestibular abnormalities, including horizontal and vertical nystagmus and an abnormal vestibuloocular reflex. In 2 of the kindreds, they found strong linkage to the CACNL1A4 locus and strong association with the expanded (CAG)n alleles, which were a single size in the 2 kindreds (22 and 23 units). These studies identified a distinct phenotype associated with SCA6, just as SCA7 (<a href="/entry/164500">164500</a>) is associated with retinopathy and blindness, and SCA2 (<a href="/entry/183090">183090</a>) is associated with pronounced slowing or loss of saccadic eye movements. One of the families in which the expanded CAG repeat was identified was the family previously reported by <a href="#41" class="mim-tip-reference" title="Zee, D. S., Yee, R. D., Cogan, D. G., Robinson, D. A., Engel, W. K. <strong>Ocular motor abnormalities in hereditary cerebellar ataxia.</strong> Brain 99: 207-234, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/990897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">990897</a>] [<a href="https://doi.org/10.1093/brain/99.2.207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="990897">Zee et al. (1976)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=990897+9403487" 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="#21" class="mim-tip-reference" title="Schols, L., Kruger, R., Amoiridis, G., Przuntek, H., Epplen, J. T., Riess, O. <strong>Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds.</strong> J. Neurol. Neurosurg. Psychiat. 64: 67-73, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9436730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9436730</a>] [<a href="https://doi.org/10.1136/jnnp.64.1.67" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9436730">Schols et al. (1998)</a> studied 9 German families with spinocerebellar ataxia-6 and found that the phenotype comprised predominantly cerebellar signs in accord with isolated cerebellar atrophy on MRI. Noncerebellar systems were only mildly affected with external ophthalmoplegia, spasticity, peripheral neuropathy, and parkinsonism. Disease onset ranged from 30 to 71 years of age and was significantly later than in other forms of autosomal dominant cerebellar ataxia. Although age at onset correlated inversely with CAG repeat length, other clinical signs and progression rate did not. By comparison with SCA1, SCA2, and SCA3, no clinical or electrophysiologic findings were specific for SCA6. Moreover, the molecular defect could not be predicted from clinical investigations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9436730" 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="Fukutake, T., Kamitsukasa, T., Arai, K., Hattori, T., Nakajima, T. <strong>A patient homozygous for the SCA6 gene with retinitis pigmentosa.</strong> Clin. Genet. 61: 375-379, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12081723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12081723</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.610510.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12081723">Fukutake et al. (2002)</a> described a 55-year-old man, the offspring of first-cousin parents, who presented not only with cerebellar ataxia and vertical antidirectional nystagmus but also with retinitis pigmentosa. The numbers of CAG repeats in the expanded alleles of the SCA6 gene were 21 on each chromosome. The retinal degeneration was thought to be secondary to a genetic disorder of either autosomal or X-linked recessive inheritance rather than SCA6. The association of retinitis pigmentosa with spinocerebellar ataxia is most characteristic of SCA7 (<a href="/entry/164500">164500</a>). Both parents had staggering gait and slurred speech late in life, but were not available for study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12081723" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 7 SCA6 patients, <a href="#35" class="mim-tip-reference" title="van de Warrenburg, B. P. C., Notermans, N. C., Schelhaas, H. J., van Alfen, N., Sinke, R. J., Knoers, N. V. A. M., Zwarts, M. J., Kremer, B. P. H. <strong>Peripheral nerve involvement in spinocerebellar ataxias.</strong> Arch. Neurol. 61: 257-261, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14967775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14967775</a>] [<a href="https://doi.org/10.1001/archneur.61.2.257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14967775">van de Warrenburg et al. (2004)</a> found no significant electrophysiologic evidence of peripheral nerve involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14967775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Pathologic Findings</em></strong></p><p>
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<a href="#33" class="mim-tip-reference" title="Tsuchiya, K., Ishikawa, K., Watabiki, S., Tone, O., Taki, K., Haga, C., Takashima, M., Ito, U., Okeda, R., Mizusawa, H., Ikeda, K. <strong>A clinical, genetic, neuropathological study in a Japanese family with SCA 6 and a review of Japanese autopsy cases of autosomal dominant cortical cerebellar atrophy.</strong> J. Neurol. Sci. 160: 54-59, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9804117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9804117</a>] [<a href="https://doi.org/10.1016/s0022-510x(98)00189-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9804117">Tsuchiya et al. (1998)</a> described a Japanese family with 2 affected sisters and an affected father. The proband developed gait disturbance at age 62 years and died at age 67 years due to subarachnoid hemorrhage. Neuropathologic examination showed severe loss of Purkinje cells in the cerebellum, predominantly in the dorsal vermis, and absence of neuronal loss in the inferior olives. The younger sister developed gait disturbance also at age 62 years. Neuroimaging at the age of 66 years showed cerebellar atrophy, predominantly in the vermis. <a href="#33" class="mim-tip-reference" title="Tsuchiya, K., Ishikawa, K., Watabiki, S., Tone, O., Taki, K., Haga, C., Takashima, M., Ito, U., Okeda, R., Mizusawa, H., Ikeda, K. <strong>A clinical, genetic, neuropathological study in a Japanese family with SCA 6 and a review of Japanese autopsy cases of autosomal dominant cortical cerebellar atrophy.</strong> J. Neurol. Sci. 160: 54-59, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9804117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9804117</a>] [<a href="https://doi.org/10.1016/s0022-510x(98)00189-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9804117">Tsuchiya et al. (1998)</a> performed a neuropathologic review of Japanese autopsy cases of autosomal dominant cortical cerebellar atrophy and found 2 patterns in the distribution of cerebellar cortical lesions. The distribution of cerebellar cortical lesions in genetically confirmed Japanese patients with SCA6 was more prominent in the vermis than in the hemisphere. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9804117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Takahashi, H., Ikeuchi, T., Honma, Y., Hayashi, S., Tsuji, S. <strong>Autosomal dominant cerebellar ataxia (SCA6): clinical, genetic and neuropathological study in a family.</strong> Acta Neuropath. 95: 333-337, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9560009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9560009</a>] [<a href="https://doi.org/10.1007/s004010050807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9560009">Takahashi et al. (1998)</a> described a family with dominantly inherited ataxia of late adult onset with affected individuals in 4 generations. Expansion of a CAG repeat in the CACNA1A gene was identified at autopsy in 1 patient, a 65-year-old woman with a disease duration of 11 years. In this patient, pathologic changes were confined to the cerebellar cortex and inferior olivary complex. The cerebellar cortex showed severe loss of Purkinje cells with proliferation of Bergmann glia, more pronounced in the superior parts of the vermis and hemispheres. In the inferior olivary complex, a reduced neuronal cell population, which could be interpreted as a change secondary to the cerebellar cortical lesion, was evident. They concluded that the pathologic phenotype of SCA6 is cerebelloolivary atrophy, or more strictly cerebellar cortical atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9560009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#25" class="mim-tip-reference" title="Soong, B., Liu, R., Wu, L., Lu, Y., Lee, H. <strong>Metabolic characterization of spinocerebellar ataxia type 6.</strong> Arch. Neurol. 58: 300-304, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11176970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11176970</a>] [<a href="https://doi.org/10.1001/archneur.58.2.300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11176970">Soong et al. (2001)</a> performed positron emission tomography using labeled glucose on 7 patients with SCA6 and 7 healthy controls to elucidate metabolic features of SCA6. They found significant hypometabolism in the patients with SCA6, ranging from 63 to 78% that of controls, in the brainstem, cerebellar hemisphere, basal ganglia, and various areas of the cortex. None of the patients manifested symptoms referable to the basal ganglia or cerebral cortices. Although <a href="#25" class="mim-tip-reference" title="Soong, B., Liu, R., Wu, L., Lu, Y., Lee, H. <strong>Metabolic characterization of spinocerebellar ataxia type 6.</strong> Arch. Neurol. 58: 300-304, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11176970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11176970</a>] [<a href="https://doi.org/10.1001/archneur.58.2.300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11176970">Soong et al. (2001)</a> postulated that the differences may be due to subclinical neuronal cell dysfunction, variation in regional blood flow, or metabolic dysfunction in structurally intact neurons, they suggested that the findings may indicate that SCA6 is not a purely cerebellar syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11176970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Christova, P., Anderson, J. H., Gomez, C. M. <strong>Impaired eye movements in presymptomatic spinocerebellar ataxia type 6.</strong> Arch. Neurol. 65: 530-536, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18413478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18413478</a>] [<a href="https://doi.org/10.1001/archneur.65.4.530" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18413478">Christova et al. (2008)</a> observed abnormal ocular motor anomalies in 4 presymptomatic SCA6 patients with CACNA1A mutations. Two patients had a low-amplitude horizontal gaze-evoked nystagmus, 1 of whom had a significantly decreased eye velocity for upward saccades and an abnormal frequency of square-wave jerks. Another had abnormal square-wave jerks, and a fourth had a reduced gain for pursuit tracking. Multivariate analysis discriminated the presymptomatic patients as a group from healthy controls and 5 manifesting SCA6 patients. <a href="#4" class="mim-tip-reference" title="Christova, P., Anderson, J. H., Gomez, C. M. <strong>Impaired eye movements in presymptomatic spinocerebellar ataxia type 6.</strong> Arch. Neurol. 65: 530-536, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18413478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18413478</a>] [<a href="https://doi.org/10.1001/archneur.65.4.530" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18413478">Christova et al. (2008)</a> suggested that early functional oculomotor impairments in SCA6 are caused by cellular dysfunction and/or loss in the posterior cerebellar vermis and flocculus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18413478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Ishikawa, K., Tanaka, H., Saito, M., Ohkoshi, N., Fujita, T., Yoshizawa, K., Ikeuchi, T., Watanabe, M., Hayashi, A., Takiyama, Y., Nishizawa, M., Nakano, I., Matsubayashi, K., Miwa, M., Shoji, S., Kanazawa, I., Tsuji, S., Mizusawa, H. <strong>Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1.</strong> Am. J. Hum. Genet. 61: 336-346, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9311738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9311738</a>] [<a href="https://doi.org/10.1086/514867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9311738">Ishikawa et al. (1997)</a> carried out genomewide linkage analysis in 15 Japanese families with autosomal dominant pure cerebellar ataxia (ADPCA). Evidence for linkage to chromosome 19p markers was found in 8 families, all of whom showed expansion of a CAG repeat in the CACNA1A gene, and combined multipoint analysis refined the candidate region to a 13.3-cM interval in 19p13.2-p13.1. 6 families were excluded for this region and 1 family was inconclusive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9311738" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Expansion of repeat sequences involving the trinucleotides CAG, CTG, CGG, or GAA is the primary cause of several dominantly inherited neurologic disorders. Among them, CAG repeat expansions have been associated with Huntington disease (HD; <a href="/entry/143100">143100</a>), X-linked spinobulbar muscular atrophy (<a href="/entry/313200">313200</a>), and several spinocerebellar ataxias. <a href="#42" class="mim-tip-reference" title="Zhuchenko, O., Bailey, J., Bonnen, P., Ashizawa, T., Stockton, D. W., Amos, C., Dobyns, W. B., Subramony, S. H., Zoghbi, H. Y., Lee, C. C. <strong>Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha(1A)-voltage-dependent calcium channel.</strong> Nature Genet. 15: 62-69, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988170</a>] [<a href="https://doi.org/10.1038/ng0197-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8988170">Zhuchenko et al. (1997)</a> noted that the CAG repeat arrays in these diseases are located in the coding region of the involved gene and are translated into polyglutamine tracts in the protein product. It is postulated that an expansion of the polyglutamine tract produces a gain of function in the protein product in each disease, accounting for the dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8988170" 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="#10" class="mim-tip-reference" title="Ishikawa, K., Fujigasaki, H., Saegusa, H., Ohwada, K., Fujita, T., Iwamoto, H., Komatsuzaki, Y., Toru, S., Toriyama, H., Watanabe, M., Ohkoshi, N., Shoji, S., Kanazawa, I., Tanabe, T., Mizusawa, H. <strong>Abundant expression and cytoplasmic aggregations of alpha-1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6.</strong> Hum. Molec. Genet. 8: 1185-1193, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369863</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369863">Ishikawa et al. (1999)</a> used RT-PCR and in situ hybridization to demonstrate that the calcium channel mRNA/protein containing the CAG repeat/polyglutamine tract is most intensely expressed in Purkinje cells of normal human brains. In SCA6 brains, numerous oval or rod-shaped aggregates were seen exclusively in the cytoplasm of Purkinje cells. These cytoplasmic inclusions were not ubiquitinated, which contrasts with the neuronal intranuclear inclusions of other CAG repeat/polyglutamine diseases. In cultured cells, formation of perinuclear aggregates of the channel protein and apoptotic cell death were seen when transfected with full-length CACNA1A coding an expanded polyglutamine tract. The authors concluded that the mechanism of neurodegeneration in SCA6 is associated with cytoplasmic aggregations of the alpha-1A calcium channel protein caused by a small CAG repeat/polyglutamine expansion in CACNA1A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Kordasiewicz, H. B., Thompson, R. M., Clark, H. B., Gomez, C. M. <strong>C-termini of P/Q-type Ca2+ channel alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity.</strong> Hum. Molec. Genet. 15: 1587-1599, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16595610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16595610</a>] [<a href="https://doi.org/10.1093/hmg/ddl080" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16595610">Kordasiewicz et al. (2006)</a> found that a 75-kD C-terminal fragment of CACNA1A, which is the location of the polyglutamine tract expanded in SCA6, is cleaved from the full-length protein and translocated to the nucleus, where it is toxic to cells when in the expanded state. The polyglutamine-mediated cell toxicity was dependent on nuclear localization, suggesting that specific processing and localization of the mutant protein is involved in the pathogenesis of SCA6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16595610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Li, L., Saegusa, H., Tanabe, T. <strong>Deficit of heat shock transcription factor 1-heat shock 70 kDa protein 1A axis determines the cell death vulnerability in a model of spinocerebellar ataxia type 6.</strong> Genes Cells 14: 1253-1269, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19817876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19817876</a>] [<a href="https://doi.org/10.1111/j.1365-2443.2009.01348.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19817876">Li et al. (2009)</a> confirmed that C-terminal fragments of CACNA1A localized predominantly to the nucleus of HEK293 cells where they existed as speckle-like structures resembling promyelocytic leukemia nuclear bodies (PMLNBs). HEK293 cells expressing an expanded (24 CAG repeats) C-terminal end of CACNA1A showed decreased viability when exposed to toxic cadmium compared to cells with nonexpanded (13 CAG) repeats. However, there were no differences in viability under normal culture conditions. Cadmium treatment also disrupted the PMLNBs and enhanced aggregation of C-terminal CACNA1A fragments, particularly in CAG-expanded cells. Immunocytochemical studies showed that cadmium-induced death was caspase-3 (CASP3; <a href="/entry/600636">600636</a>)-dependent, indicating apoptosis. Gene expression studies showed downregulation of the HSF1 (<a href="/entry/140580">140580</a>)-HSPA1A (<a href="/entry/140550">140550</a>) axis as an event in 24-CAG repeat cells that appeared to be critical for cellular toxicity. The findings were consistent with SCA6 pathogenesis being related to polyglutamine diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19817876" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of SCA6 in the families reported by <a href="#42" class="mim-tip-reference" title="Zhuchenko, O., Bailey, J., Bonnen, P., Ashizawa, T., Stockton, D. W., Amos, C., Dobyns, W. B., Subramony, S. H., Zoghbi, H. Y., Lee, C. C. <strong>Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha(1A)-voltage-dependent calcium channel.</strong> Nature Genet. 15: 62-69, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988170</a>] [<a href="https://doi.org/10.1038/ng0197-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8988170">Zhuchenko et al. (1997)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8988170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#42" class="mim-tip-reference" title="Zhuchenko, O., Bailey, J., Bonnen, P., Ashizawa, T., Stockton, D. W., Amos, C., Dobyns, W. B., Subramony, S. H., Zoghbi, H. Y., Lee, C. C. <strong>Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha(1A)-voltage-dependent calcium channel.</strong> Nature Genet. 15: 62-69, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988170</a>] [<a href="https://doi.org/10.1038/ng0197-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8988170">Zhuchenko et al. (1997)</a> performed a genotyping survey using polymorphic CAG repeats and DNA samples from patients with late-onset neurogenic diseases. In the course of these studies they found an expansion of a CAG repeat in the human alpha-1A-voltage-dependent Ca(2+) channel gene (<a href="/entry/601011#0007">601011.0007</a>), which maps to 19p13. They identified 6 isoforms of the human alpha-1A calcium channel subunit. The CAG repeat was within the open reading frame and was predicted to encode glutamine in 3 of the isoforms. In 8 families, the CAG repeat expansion of the Ca(2+) channel gene was the mutation mechanism for SCA6. One of the families had been reported by <a href="#28" class="mim-tip-reference" title="Subramony, S. H., Fratkin, J. D., Manyam, B. V., Currier, R. D. <strong>Dominantly inherited cerebello-olivary atrophy is not due to a mutation at the spinocerebellar ataxia-I, Machado-Joseph disease, or dentato-rubro-pallido-luysian atrophy locus.</strong> Movement Disorders 11: 174-180, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8684388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8684388</a>] [<a href="https://doi.org/10.1002/mds.870110210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8684388">Subramony et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8684388+8988170" 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>Analysis of CAG repeat expansion in the CACNL1A4 gene by <a href="#11" class="mim-tip-reference" title="Ishikawa, K., Tanaka, H., Saito, M., Ohkoshi, N., Fujita, T., Yoshizawa, K., Ikeuchi, T., Watanabe, M., Hayashi, A., Takiyama, Y., Nishizawa, M., Nakano, I., Matsubayashi, K., Miwa, M., Shoji, S., Kanazawa, I., Tsuji, S., Mizusawa, H. <strong>Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1.</strong> Am. J. Hum. Genet. 61: 336-346, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9311738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9311738</a>] [<a href="https://doi.org/10.1086/514867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9311738">Ishikawa et al. (1997)</a> revealed expansion in 8 of 15 Japanese families with autosomal dominant cerebellar ataxia; all affected individuals had larger alleles (range of CAG repeats 21 to 25), compared with alleles observed in neurologically normal Japanese (range 5 to 20 repeats). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9311738" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Takiyama, Y., Sakoe, K., Namekawa, M., Soutome, M., Esumi, E., Ogawa, T., Ishikawa, K., Mizusawa, H., Nakano, I., Nishizawa, M. <strong>A Japanese family with spinocerebellar ataxia type 6 which includes three individuals homozygous for an expanded CAG repeat in the SCA6/CACNL1A4 gene.</strong> J. Neurol. Sci. 158: 141-147, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9702684/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9702684</a>] [<a href="https://doi.org/10.1016/s0022-510x(98)00108-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9702684">Takiyama et al. (1998)</a> studied a Japanese family that included 13 persons with SCA6 in 5 generations. Molecular testing revealed that the patients carried the smallest known expanded CAG repeat (21 repeat units). The clinical features of these patients included predominantly cerebellar ataxia with onset late in adult life and a very slowly progressive course. In addition, this SCA6 family showed some characteristic clinical and genetic features, including (1) apparent lack of genetic anticipation, with an intergenerationally stable CAG repeat size, and (2) down-beat nystagmus and diabetes mellitus in some of the SCA6 patients. They identified 3 individuals homozygous for an expanded CAG repeat (21/21) in the CACNL1A4 gene; 2 were symptomatic and 1 was asymptomatic at age 50 years. There was no apparent difference in clinical phenotype between the homozygotes and the heterozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9702684" 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="Fukutake, T., Kamitsukasa, T., Arai, K., Hattori, T., Nakajima, T. <strong>A patient homozygous for the SCA6 gene with retinitis pigmentosa.</strong> Clin. Genet. 61: 375-379, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12081723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12081723</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.610510.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12081723">Fukutake et al. (2002)</a> stated that 11 patients with genetically verified SCA6 who were homozygous or compound heterozygous for (CAG)n repeats in the CACNA1A gene (<a href="/entry/601011#0007">601011.0007</a>) had previously been reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12081723" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a family in which multiple members had severe progressive cerebellar ataxia involving the trunk, extremities, and speech, <a href="#40" class="mim-tip-reference" title="Yue, Q., Jen, J. C., Nelson, S. F., Baloh, R. W. <strong>Progressive ataxia due to a missense mutation in a calcium-channel gene.</strong> Am. J. Hum. Genet. 61: 1078-1087, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9345107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9345107</a>] [<a href="https://doi.org/10.1086/301613" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9345107">Yue et al. (1997)</a> identified a 1152G-A transition in exon 6 of the CACNA1A gene, resulting in a gly293-to-arg substitution (G293R; <a href="/entry/601011#0009">601011.0009</a>). The CAG(n) repeat expansion associated with SCA6 was not present in any family member. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9345107" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a large Portuguese family in which 17 patients over 4 generations were affected with hemiplegic migraine and/or progressive SCA6, <a href="#1" class="mim-tip-reference" title="Alonso, I., Barros, J., Tuna, A., Coelho, J., Sequeiros, J., Silveira, I., Coutinho, P. <strong>Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family.</strong> Arch. Neurol. 60: 610-614, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707077</a>] [<a href="https://doi.org/10.1001/archneur.60.4.610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12707077">Alonso et al. (2003)</a> found that all patients shared a common haplotype and carried an arg583-to-gln mutation in the CACNA1A gene (R583Q; <a href="/entry/601011#0018">601011.0018</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12707077" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Anticipation</em></strong></p><p>
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In his studies of families with SCA6, <a href="#42" class="mim-tip-reference" title="Zhuchenko, O., Bailey, J., Bonnen, P., Ashizawa, T., Stockton, D. W., Amos, C., Dobyns, W. B., Subramony, S. H., Zoghbi, H. Y., Lee, C. C. <strong>Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha(1A)-voltage-dependent calcium channel.</strong> Nature Genet. 15: 62-69, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988170</a>] [<a href="https://doi.org/10.1038/ng0197-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8988170">Zhuchenko et al. (1997)</a> noted that there seemed to be a correlation between the repeat number and earlier onset of the disorder. <a href="#17" class="mim-tip-reference" title="Matsuyama, Z., Kawakami, H., Maruyama, H., Izumi, Y., Komure, O., Udaka, F., Kameyama, M., Nishio, T., Kuroda, Y., Nishimura, M., Nakamura, S. <strong>Molecular features of the CAG repeats of spinocerebellar ataxia 6 (SCA6).</strong> Hum. Molec. Genet. 6: 1283-1287, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259274</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259274">Matsuyama et al. (1997)</a> analyzed 60 SCA6 individuals from 39 independent Japanese SCA6 families and found that the CAG repeat length in the CACNL1A4 gene was inversely correlated with age of onset. SCA6 chromosomes contained 21 to 30 repeat units, whereas normal chromosomes displayed 6 to 17 repeats. There was no overlap between the normal and affected CAG repeat number. Anticipation was observed clinically in all 8 parent-child pairs examined; the mean age of onset was significantly lower (P = 0.0042) in children than in parents. However, a parent-child analysis showed an increase in the expansion of CAG repeats only in 1 pair and no diminution in any affected cases. The results suggested that factors other than CAG repeats may produce the clinical anticipation. A homozygotic case could not demonstrate unequivocal gene dosage effect on the age of onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8988170+9259274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the 8 families with SCA6 reported by <a href="#11" class="mim-tip-reference" title="Ishikawa, K., Tanaka, H., Saito, M., Ohkoshi, N., Fujita, T., Yoshizawa, K., Ikeuchi, T., Watanabe, M., Hayashi, A., Takiyama, Y., Nishizawa, M., Nakano, I., Matsubayashi, K., Miwa, M., Shoji, S., Kanazawa, I., Tsuji, S., Mizusawa, H. <strong>Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1.</strong> Am. J. Hum. Genet. 61: 336-346, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9311738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9311738</a>] [<a href="https://doi.org/10.1086/514867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9311738">Ishikawa et al. (1997)</a>, inverse correlation between the CAG-repeat number and the age of onset was found in affected individuals with expansion. The number of CAG repeats in expanded chromosomes was completely stable within each family, which was consistent with the fact that anticipation was not statistically proven in these SCA6 families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9311738" 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="#18" class="mim-tip-reference" title="Riess, O., Schols, L., Bottger, H., Nolte, D., Viera-Saecker, A. M. M., Schimming, C., Kreuz, F., Macek, M., Jr., Krebsova, A., Macek, M., Sr., Klockgether, T., Zuhlke, C., Laccone, F. A. <strong>SCA6 is caused by moderate CAG expansion in the alpha(1A)-voltage-dependent calcium channel gene.</strong> Hum. Molec. Genet. 6: 1289-1293, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259275</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1289" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259275">Riess et al. (1997)</a> observed the trinucleotide expansion in 4 ataxia patients without obvious family history of the disease, indicating the necessity to search for the SCA6 (CAG)n expansion even in sporadic patients. In their series of 32 patients, onset was usually late and the (CAG)n stretch varied between 22 and 28 trinucleotide units, the shortest trinucleotide repeat expansion causing spinocerebellar ataxia. Analyzing 248 apparently healthy octogenarians, <a href="#18" class="mim-tip-reference" title="Riess, O., Schols, L., Bottger, H., Nolte, D., Viera-Saecker, A. M. M., Schimming, C., Kreuz, F., Macek, M., Jr., Krebsova, A., Macek, M., Sr., Klockgether, T., Zuhlke, C., Laccone, F. A. <strong>SCA6 is caused by moderate CAG expansion in the alpha(1A)-voltage-dependent calcium channel gene.</strong> Hum. Molec. Genet. 6: 1289-1293, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259275</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1289" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259275">Riess et al. (1997)</a> found 1 allele of 18 repeats, the longest normal CAG repeat in the CACNL1A4 gene reported to that time. They could demonstrate no repeat instability of the expanded allele on transmission and no repeat instability was found for the normal allele in 431 meioses in the CEPH families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259275" 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="#16" class="mim-tip-reference" title="Mariotti, C., Gellera, C., Grisoli, M., Mineri, R., Castucci, A., Di Donato, S. <strong>Pathogenic effect of an intermediate-size SCA-6 allele (CAG)19 in a homozygous patient.</strong> Neurology 57: 1502-1504, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11673601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11673601</a>] [<a href="https://doi.org/10.1212/wnl.57.8.1502" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11673601">Mariotti et al. (2001)</a> described an Italian family in which 1 member carried a fully expanded SCA6 allele with 26 CAG repeats, whereas the other affected family member was homozygous for an intermediate allele of 19 CAG repeats. Three family members, heterozygous for the intermediate allele, were clinically unaffected. The findings demonstrated a dose-dependent pathogenic effect of an intermediate CAG expansion in the SCA6 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11673601" 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="#30" class="mim-tip-reference" title="Takahashi, H., Ishikawa, K., Tsutsumi, T., Fujigasaki, H., Kawata, A., Okiyama, R., Fujita, T., Yoshizawa, K., Yamaguchi, S., Tomiyasu, H., Yoshii, F., Mitani, K., Shimizu, N., Yamazaki, M., Miyamoto, T., Orimo, T., Shoji, S., Kitamura, K., Mizusawa, H. <strong>A clinical and genetic study in a large cohort of patients with spinocerebellar ataxia type 6.</strong> J. Hum. Genet. 49: 256-264, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15362569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15362569</a>] [<a href="https://doi.org/10.1007/s10038-004-0142-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15362569">Takahashi et al. (2004)</a> retrospectively analyzed 140 patients with SCA6. They observed an inverse correlation between the age at onset and the length of the expanded allele, and also between the age at onset and the sum of CAG repeats in the normal and the expanded alleles. The ages at onset of 4 homozygous patients correlated better with the sum of CAG repeats in both alleles than with the expanded allele calculated from heterozygous SCA6 patients. Clinically, unsteadiness of gait was the main initial symptom, followed by vertigo and oscillopsia, and cerebellar signs were detected in nearly 100% of the patients. In contrast, extracerebellar signs were relatively mild and infrequent. Neuro-otologic examination performed in 22 patients suggested that the abnormalities of ocular movements were purely cerebellar in nature. There was a close relationship between down-beat positioning nystagmus and positioning vertigo, which became more common in the later stage. <a href="#30" class="mim-tip-reference" title="Takahashi, H., Ishikawa, K., Tsutsumi, T., Fujigasaki, H., Kawata, A., Okiyama, R., Fujita, T., Yoshizawa, K., Yamaguchi, S., Tomiyasu, H., Yoshii, F., Mitani, K., Shimizu, N., Yamazaki, M., Miyamoto, T., Orimo, T., Shoji, S., Kitamura, K., Mizusawa, H. <strong>A clinical and genetic study in a large cohort of patients with spinocerebellar ataxia type 6.</strong> J. Hum. Genet. 49: 256-264, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15362569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15362569</a>] [<a href="https://doi.org/10.1007/s10038-004-0142-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15362569">Takahashi et al. (2004)</a> concluded that total number of CAG repeat units in both alleles is a good parameter for assessment of age at onset in SCA6, including in homozygous patients. In addition, clinical and neuro-otologic examination suggested that SCA6 is a disease with predominantly cerebellar dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15362569" 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="#34" class="mim-tip-reference" title="van de Warrenburg, B. P. C., Hendriks, H., Durr, A., van Zuijlen, M. C. A., Stevanin, G., Camuzat, A., Sinke, R. J., Brice, A., Kremer, B. P. H. <strong>Age at onset variance analysis in spinocerebellar ataxias: a study in a Dutch-French cohort.</strong> Ann. Neurol. 57: 505-512, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15747371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15747371</a>] [<a href="https://doi.org/10.1002/ana.20424" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15747371">Van de Warrenburg et al. (2005)</a> applied statistical analysis to examine the relationship between age at onset and number of expanded triplet repeats from a Dutch-French cohort of 802 patients with SCA1 (138 patients), SCA2 (166 patients), SCA3 (342 patients), SCA6 (53 patients), and SCA7 (103 patients). The size of the expanded repeat explained 66 to 75% of the variance in age at onset for SCA1, SCA2, and SCA7, but less than 50% for SCA3 and SCA6. The relation between age at onset and CAG repeat was similar for all groups except for SCA2, suggesting that the polyglutamine repeat in the ataxin-2 protein exerts its pathologic effect in a different way. A contribution of the nonexpanded allele to age at onset was observed for only SCA1 and SCA6. <a href="#34" class="mim-tip-reference" title="van de Warrenburg, B. P. C., Hendriks, H., Durr, A., van Zuijlen, M. C. A., Stevanin, G., Camuzat, A., Sinke, R. J., Brice, A., Kremer, B. P. H. <strong>Age at onset variance analysis in spinocerebellar ataxias: a study in a Dutch-French cohort.</strong> Ann. Neurol. 57: 505-512, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15747371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15747371</a>] [<a href="https://doi.org/10.1002/ana.20424" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15747371">Van de Warrenburg et al. (2005)</a> acknowledged that their results were purely mathematical, but suggested that they reflected biologic variations among the diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15747371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#20" class="mim-tip-reference" title="Schols, L., Amoiridis, G., Buttner, T., Przuntek, H., Epplen, J. T., Riess, O. <strong>Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes?</strong> Ann. Neurol. 42: 924-932, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9403486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9403486</a>] [<a href="https://doi.org/10.1002/ana.410420615" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9403486">Schols et al. (1997)</a> compared clinical, electrophysiologic, and MRI findings to identify phenotypic characteristics of genetically defined SCA subtypes. Slow saccades, hyporeflexia, myoclonus, and action tremor suggested SCA2. SCA3 (<a href="/entry/109150">109150</a>) patients frequently developed diplopia, severe spasticity or pronounced peripheral neuropathy, and impaired temperature discrimination, apart from ataxia. SCA6 presented with a predominantly cerebellar syndrome, and patients often had onset after 55 years of age. SCA1 (<a href="/entry/164400">164400</a>) was characterized by markedly prolonged peripheral and central motor conduction times in motor evoked potentials. MRI scans showed pontine and cerebellar atrophy in SCA1 and SCA2. In SCA3, enlargement of the fourth ventricle was the main sequel of atrophy. SCA6 presented with pure cerebellar atrophy on MRI. Overlap among the 4 SCA subtypes was broad, however. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9403486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an investigation of oculomotor function, <a href="#3" class="mim-tip-reference" title="Buttner, N., Geschwind, D., Jen, J. C., Perlman, S., Pulst, S. M., Baloh, R. W. <strong>Oculomotor phenotypes in autosomal dominant ataxias.</strong> Arch. Neurol. 55: 1353-1357, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9779665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9779665</a>] [<a href="https://doi.org/10.1001/archneur.55.10.1353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9779665">Buttner et al. (1998)</a> found that all 3 patients with SCA1, all 7 patients with SCA3, and all 5 patients with SCA6 had gaze-evoked nystagmus. Three of 5 patients with SCA2 did not have gaze-evoked nystagmus, perhaps because they could not generate corrective fast components. Rebound nystagmus occurred in all SCA3 patients, 33% of SCA1 patients, 40% of SCA6 patients, and none of SCA2. Spontaneous downbeat nystagmus only occurred in SCA6. Peak saccade velocity was decreased in 100% of patients with SCA2, 1 patient with SCA1, and no patients with SCA3 or SCA6. Saccade hypermetria was found in all types, but was most common in SCA3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9779665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using an analysis of covariance and multivariate models to examine symptom severity in 526 patients with SCA1, SCA2, SCA3, or SCA6, <a href="#19" class="mim-tip-reference" title="Schmitz-Hubsch, T., Coudert, M., Bauer, P., Giunti, P., Globas, C., Baliko, L., Filla, A., Mariotti, C., Rakowicz, M., Charles, P., Ribai, P., Szymanski, S., and 19 others. <strong>Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms.</strong> Neurology 71: 982-989, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18685131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18685131</a>] [<a href="https://doi.org/10.1212/01.wnl.0000325057.33666.72" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18685131">Schmitz-Hubsch et al. (2008)</a> found that repeat length of the expanded allele, age at onset, and disease duration explained 60.4% of the ataxia score in SCA1, 45.4% in SCA2, 46.8% in SCA3. However, only age at onset and disease duration appeared to explain 33.7% of the score in SCA6. Similar findings were obtained for nonataxic symptoms. The study suggested that SCA1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18685131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a family initially classified as autosomal dominant cerebellar ataxia of unknown type, <a href="#12" class="mim-tip-reference" title="Jodice, C., Mantuano, E., Veneziano, L., Trettel, F., Sabbadini, G., Calandriello, L., Francia, A., Spadaro, M., Pierelli, F., Salvi, F., Ophoff, R. A., Frants, R. R., Frontali, M. <strong>Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p.</strong> Hum. Molec. Genet. 6: 1973-1978, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9302278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9302278</a>] [<a href="https://doi.org/10.1093/hmg/6.11.1973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9302278">Jodice et al. (1997)</a> found an intergenerational allele size change in the CACNA1A gene, showing that a (CAG)20 allele (<a href="/entry/601011#0008">601011.0008</a>) was associated with the phenotype of episodic ataxia type 2 (EA2; <a href="/entry/108500">108500</a>) and a (CAG)25 allele with progressive cerebellar ataxia. These results suggested that EA2 and SCA6 are the same disorder with a high phenotypic variability, at least partly related to the number of repeats, and suggested that the small expansions may not be as stable as previously reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9302278" 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="#24" class="mim-tip-reference" title="Sinke, R. J., Ippel, E. F., Diepstraten, C. M., Beemer, F. A., Wokke, J. H. J., van Hilten, B. J., Knoers, N. V. A. M., Ploos van Amstel, H. K., Kremer, H. P. H. <strong>Clinical and molecular correlations in spinocerebellar ataxia type 6: a study of 24 Dutch families.</strong> Arch. Neurol. 58: 1839-1844, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11708993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11708993</a>] [<a href="https://doi.org/10.1001/archneur.58.11.1839" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11708993">Sinke et al. (2001)</a> described a study of 24 Dutch families with SCA6. Clinical analysis identified SCA6 as a late-onset ataxia in which eye movement abnormalities are prominent and consistent early manifestations. Some patients had ataxia combined with episodic headaches or nausea, suggesting an overlap among SCA6, episodic ataxia type 2, and familial hemiplegic migraine (<a href="/entry/141500">141500</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11708993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a large Portuguese family in which 17 patients over 4 generations were affected with hemiplegic migraine and/or progressive SCA6, <a href="#1" class="mim-tip-reference" title="Alonso, I., Barros, J., Tuna, A., Coelho, J., Sequeiros, J., Silveira, I., Coutinho, P. <strong>Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family.</strong> Arch. Neurol. 60: 610-614, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707077</a>] [<a href="https://doi.org/10.1001/archneur.60.4.610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12707077">Alonso et al. (2003)</a> found that all patients shared a common haplotype and carried an arg583-to-gln mutation in the CACNA1A gene (R583Q; <a href="/entry/601011#0018">601011.0018</a>). Four patients, all under the age of 18 years, had only hemiplegic migraine, 8 patients had isolated progressive cerebellar ataxia, and 5 patients had both hemiplegic migraine and cerebellar ataxia. Several patients reported symptoms triggered by minor head trauma. <a href="#1" class="mim-tip-reference" title="Alonso, I., Barros, J., Tuna, A., Coelho, J., Sequeiros, J., Silveira, I., Coutinho, P. <strong>Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family.</strong> Arch. Neurol. 60: 610-614, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707077</a>] [<a href="https://doi.org/10.1001/archneur.60.4.610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12707077">Alonso et al. (2003)</a> suggested that EA2, SCA6, and familial hemiplegic migraine are not only allelic disorders, but may be the same disorder with great phenotypic variability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12707077" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#18" class="mim-tip-reference" title="Riess, O., Schols, L., Bottger, H., Nolte, D., Viera-Saecker, A. M. M., Schimming, C., Kreuz, F., Macek, M., Jr., Krebsova, A., Macek, M., Sr., Klockgether, T., Zuhlke, C., Laccone, F. A. <strong>SCA6 is caused by moderate CAG expansion in the alpha(1A)-voltage-dependent calcium channel gene.</strong> Hum. Molec. Genet. 6: 1289-1293, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259275</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1289" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259275">Riess et al. (1997)</a> found that the SCA6 mutation accounts for approximately 10% of autosomal dominant SCA in Germany. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259275" 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>Studying 77 German families with autosomal dominant cerebellar ataxia of SCA types 1, 2, 3, and 6, <a href="#20" class="mim-tip-reference" title="Schols, L., Amoiridis, G., Buttner, T., Przuntek, H., Epplen, J. T., Riess, O. <strong>Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes?</strong> Ann. Neurol. 42: 924-932, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9403486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9403486</a>] [<a href="https://doi.org/10.1002/ana.410420615" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9403486">Schols et al. (1997)</a> found that the SCA1 mutation accounted for 9%, SCA2 for 10%, SCA3 for 42%, and SCA6 for 22%. There was no family history of ataxia in 7 of 27 SCA6 patients. Age at onset correlated inversely with repeat length in all subtypes, yet the average effect of 1 CAG unit on age of onset was different for each SCA subtype. <a href="#21" class="mim-tip-reference" title="Schols, L., Kruger, R., Amoiridis, G., Przuntek, H., Epplen, J. T., Riess, O. <strong>Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds.</strong> J. Neurol. Neurosurg. Psychiat. 64: 67-73, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9436730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9436730</a>] [<a href="https://doi.org/10.1136/jnnp.64.1.67" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9436730">Schols et al. (1998)</a> investigated the SCA6 mutation (expanded repeat in the CACNA1A gene) in 69 German families with autosomal dominant cerebellar ataxia and 61 patients with idiopathic sporadic cerebellar ataxia. The expanded CAG repeat was found in 9 of 69 families, as well as in 4 patients with sporadic disease. <a href="#21" class="mim-tip-reference" title="Schols, L., Kruger, R., Amoiridis, G., Przuntek, H., Epplen, J. T., Riess, O. <strong>Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds.</strong> J. Neurol. Neurosurg. Psychiat. 64: 67-73, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9436730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9436730</a>] [<a href="https://doi.org/10.1136/jnnp.64.1.67" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9436730">Schols et al. (1998)</a> noted that in Germany, SCA6 accounts for about 13% of families with autosomal dominant cerebellar ataxia. However, up to 30% of SCA6 kindreds may be misdiagnosed clinically as sporadic disease due to late manifestation in apparently healthy parents. Genetic testing was therefore recommended for the SCA6 mutation also in patients with putative sporadic ataxia. In a study of apparently idiopathic sporadic cerebellar ataxia involving 124 patients, <a href="#22" class="mim-tip-reference" title="Schols, L., Szymanski, S., Peters, S., Przuntek, H., Epplen, J. T., Hardt, C., Riess, O. <strong>Genetic background of apparently idiopathic sporadic cerebellar ataxia.</strong> Hum. Genet. 107: 132-137, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030410</a>] [<a href="https://doi.org/10.1007/s004390000346" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11030410">Schols et al. (2000)</a> found the SCA6 mutation in 9 patients with disease onset between 47 and 68 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9403486+9436730+11030410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using an intragenic marker, D19S1150, and 2 markers (DS19S221 and DS19S226) bracketing 3 cM on either side, <a href="#7" class="mim-tip-reference" title="Dichgans, M., Schols, L., Herzog, J., Stevanin, G., Weirich-Schwaiger, H., Rouleau, G., Burk, K., Klockgether, T., Zuhlke, C., Laccone, F., Riess, O., Gasser, T. <strong>Spinocerebellar ataxia type 6: evidence for a strong founder effect among German families.</strong> Neurology 52: 849-852, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10078738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10078738</a>] [<a href="https://doi.org/10.1212/wnl.52.4.849" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10078738">Dichgans et al. (1999)</a> found a common haplotype in 7 of 12 German families segregating SCA6. This finding, as well as a clustering of the families from Northrhine-Westfalia, strongly suggests a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10078738" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>From their study of 15 families with autosomal dominant cerebellar ataxia, <a href="#11" class="mim-tip-reference" title="Ishikawa, K., Tanaka, H., Saito, M., Ohkoshi, N., Fujita, T., Yoshizawa, K., Ikeuchi, T., Watanabe, M., Hayashi, A., Takiyama, Y., Nishizawa, M., Nakano, I., Matsubayashi, K., Miwa, M., Shoji, S., Kanazawa, I., Tsuji, S., Mizusawa, H. <strong>Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1.</strong> Am. J. Hum. Genet. 61: 336-346, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9311738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9311738</a>] [<a href="https://doi.org/10.1086/514867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9311738">Ishikawa et al. (1997)</a> concluded that more than half of Japanese cases of ADPCA map to 19p and are strongly associated with a mild CAG expansion in the SCA6/CACNL1A4 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9311738" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Watanabe, H., Tanaka, F., Matsumoto, M., Doyu, M., Ando, T., Mitsuma, T., Sobue, G. <strong>Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia type 6.</strong> Clin. Genet. 53: 13-19, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9550356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9550356</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1998.531530104.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9550356">Watanabe et al. (1998)</a> investigated 101 kindreds with spinocerebellar ataxias from the central Honshu island of Japan, using a molecular diagnostic approach with amplification of the CAG trinucleotide repeat of the causative genes. Machado-Joseph disease (<a href="/entry/109150">109150</a>) was the most prevalent (33.7%) form, followed by dentatorubral-pallidoluysian atrophy (<a href="/entry/125370">125370</a>; 19.8%), SCA6 (5.9%), and SCA2 (5.9%). All 7 SCA6 patients had expanded alleles of the CACNL1A4 gene and signs of a pure cerebellar syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9550356" 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>Among 202 Japanese and 177 Caucasian families with autosomal dominant SCA, <a href="#31" class="mim-tip-reference" title="Takano, H., Cancel, G., Ikeuchi, T., Lorenzetti, D., Mawad, R., Stevanin, G., Didierjean, O., Durr, A., Oyake, M., Shimohata, T., Sasaki, R., Koide, R., Igarashi, S., Hayashi, S., Takiyama, Y., Nishizawa, M., Tanaka, H., Zoghbi, H., Brice, A., Tsuji, S. <strong>Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations.</strong> Am. J. Hum. Genet. 63: 1060-1066, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9758625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9758625</a>] [<a href="https://doi.org/10.1086/302067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9758625">Takano et al. (1998)</a> found that the prevalence of SCA6 was significantly higher in the Japanese population (11%) compared to Caucasian population (5%). This corresponded to higher frequencies of large normal CACNA1A CAG repeat alleles (greater than 13 repeats) in Japanese controls compared to Caucasian controls. The findings suggested that large normal alleles contribute to the generation of expanded alleles that lead to dominant SCA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9758625" 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="#39" class="mim-tip-reference" title="Yabe, I., Sasaki, H., Yamashita, I., Tashiro, K., Takei, A., Suzuki, Y., Kida, H., Takiyama, Y., Nishizawa, M., Hokezu, Y., Nagamatsu, K., Oda, T., Ohnishi, A., Inoue, I., Hata, A. <strong>Predisposing chromosome for spinocerebellar ataxia type 6 (SCA6) in Japanese.</strong> J. Med. Genet. 38: 328-333, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11403042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11403042</a>] [<a href="https://doi.org/10.1136/jmg.38.5.328" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11403042">Yabe et al. (2001)</a> studied 21 Japanese families with SCA6 and found one of 2 haplotypes in each family. They suggested a mechanism by which the second haplotype could have arisen from a single common haplotype, and that therefore there was evidence of a founder effect in SCA6 families in Japan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11403042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Storey, E., du Sart, D., Shaw, J. H., Lorentzos, P., Kelly, L., Gardner, R. J. M., Forrest, S. M., Biros, I., Nicholson, G. A. <strong>Frequency of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Australian patients with spinocerebellar ataxia.</strong> Am. J. Med. Genet. 95: 351-357, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11186889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11186889</a>] [<a href="https://doi.org/10.1002/1096-8628(20001211)95:4<351::aid-ajmg10>3.0.co;2-r" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11186889">Storey et al. (2000)</a> examined the frequency of mutations for SCA types 1, 2, 3, 6, and 7 in southeastern Australia. Of 63 pedigrees or individuals with positive tests, 30% had SCA1, 15% had SCA2, 22% had SCA3, 30% had SCA6, and 3% had SCA7. Ethnic origin was of importance in determining SCA type: 4 of 9 SCA2 index cases were of Italian origin, and 4 of 14 SCA3 index cases were of Chinese origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11186889" 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="#24" class="mim-tip-reference" title="Sinke, R. J., Ippel, E. F., Diepstraten, C. M., Beemer, F. A., Wokke, J. H. J., van Hilten, B. J., Knoers, N. V. A. M., Ploos van Amstel, H. K., Kremer, H. P. H. <strong>Clinical and molecular correlations in spinocerebellar ataxia type 6: a study of 24 Dutch families.</strong> Arch. Neurol. 58: 1839-1844, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11708993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11708993</a>] [<a href="https://doi.org/10.1001/archneur.58.11.1839" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11708993">Sinke et al. (2001)</a> determined that SCA6 accounted for approximately 11% of all Dutch families with autosomal dominant cerebellar ataxia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11708993" 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>Among 74 Taiwanese families with autosomal dominant cerebellar ataxia and 49 Taiwanese patients with sporadic ataxia, <a href="#26" class="mim-tip-reference" title="Soong, B., Lu, Y., Choo, K., Lee, H. <strong>Frequency analysis of autosomal dominant cerebellar ataxias in Taiwanese patients and clinical and molecular characterization of spinocerebellar ataxia type 6.</strong> Arch. Neurol. 58: 1105-1109, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11448300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11448300</a>] [<a href="https://doi.org/10.1001/archneur.58.7.1105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11448300">Soong et al. (2001)</a> determined that SCA6 accounted for 10.8% of the familial cases and 4.1% of the sporadic cases. The prevalence of SCA3 was 47.3%, followed by SCA2 (10.8%), SCA1 (5.4%), SCA7 (2.7%), and DRPLA (1.4%). In the families with SCA6, there was significant anticipation in the absence of genetic instability. The same allele of intragenic marker D19S1150 was found in 70% of the SCA6 patients, suggesting a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11448300" 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>Of 253 unrelated Korean patients with progressive cerebellar ataxia, <a href="#14" class="mim-tip-reference" title="Lee, W. Y., Jin, D. K., Oh, M. R., Lee, J. E., Song, S. M., Lee, E. A., Kim, G., Chung, J. S., Lee, K. H. <strong>Frequency analysis and clinical characterization of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Korean patients.</strong> Arch. Neurol. 60: 858-863, 2003. Note: Erratum: Arch. Neurol. 60: 1256 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12810491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12810491</a>] [<a href="https://doi.org/10.1001/archneur.60.6.858" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12810491">Lee et al. (2003)</a> identified 52 (20.6%) with expanded CAG repeats. The most frequent SCA type was SCA2 (33%), followed by SCA3 (29%), SCA6 (19%), SCA1 (12%), and SCA7 (8%). There were characteristic clinical features, such as hypotonia and optic atrophy for SCA1, hyporeflexia for SCA2, nystagmus, bulging eye, and dystonia for SCA3, and macular degeneration for SCA7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12810491" 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 haplotype analysis of 12 Dutch SCA6 families confirmed by genotype, <a href="#36" class="mim-tip-reference" title="Verbeek, D. S., Piersma, S. J., Hennekam, E. F. A. M., Ippel, E. F., Pearson, P. L., Sinke, R. J. <strong>Haplotype study in Dutch SCA3 and SCA6 families: evidence for common founder mutations.</strong> Europ. J. Hum. Genet. 12: 441-446, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15026782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15026782</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15026782">Verbeek et al. (2004)</a> found that 8 families (approximately 70%) shared a region between markers D19S1165 and D19S840, including the SCA6 gene, which was not observed in 80 control chromosomes. Two additional SCA6 families shared an extended haplotype. Genealogic research showed that most of the families were clustered in North Holland. The authors noted that mutation in the SCA6 gene occurs in 23.4% of the Dutch autosomal dominant cerebellar ataxia population. Similar haplotype results were found for SCA3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15026782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a population-based study in Northeastern England, <a href="#5" class="mim-tip-reference" title="Craig, K., Keers, S. M., Archibald, K., Curtis, A., Chinnery, P. F. <strong>Molecular epidemiology of spinocerebellar ataxia type 6.</strong> Ann. Neurol. 55: 752-755, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15122720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15122720</a>] [<a href="https://doi.org/10.1002/ana.20110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15122720">Craig et al. (2004)</a> estimated that the number of people with or at risk for SCA6 was at least 5.21/100,000, or 1 in 19,210. Haplotype analysis suggested a founder effect, and 56% of affected individuals had an identical CAG repeat length (21 repeats). The clinical phenotype of this group was homogeneous. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15122720" 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="#23" class="mim-tip-reference" title="Shimizu, Y., Yoshida, K., Okano, T., Ohara, S., Hashimoto, T., Fukushima, Y., Ikeda, S. <strong>Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families.</strong> J. Hum. Genet. 49: 610-616, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15480876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15480876</a>] [<a href="https://doi.org/10.1007/s10038-004-0196-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15480876">Shimizu et al. (2004)</a> estimated the prevalence of SCA in the Nagano prefecture of Japan to be at least 22 per 100,000. Thirty-one of 86 families (36%) were positive for SCA disease-causing repeat expansions: SCA6 was the most common form (19%), followed by DRPLA (10%), SCA3 (3%), SCA1 (2%), and SCA2 (1%). The authors noted that the prevalence of SCA3 was lower compared to other regions in Japan, and that the number of genetically undetermined SCA families in Nagano was much higher than in other regions. Nagano is the central district of the main island of Japan, located in a mountainous area surrounded by the Japanese Alps. The restricted geography suggested that founder effects may have contributed to the high frequency of genetically undetermined ADCA families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15480876" 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>Among 113 Japanese families from the island of Hokkaido with autosomal dominant SCA, <a href="#2" class="mim-tip-reference" title="Basri, R., Yabe, I., Soma, H., Sasaki, H. <strong>Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families.</strong> J. Hum. Genet. 52: 848-855, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17805477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17805477</a>] [<a href="https://doi.org/10.1007/s10038-007-0182-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17805477">Basri et al. (2007)</a> found that SCA6 was the most common form of the disorder, identified in 35 (31%) families. Thirty (27%) families had SCA3, 11 (10%) had SCA1, 5 (4%) had SCA2, 5 (4%) had DRPLA, 10 (9%) had 16q22-linked SCA (<a href="/entry/117210">117210</a>), and 1 (1%) had SCA14 (<a href="/entry/605361">605361</a>). The specific disorder could not be identified in 16 (14%) families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17805477" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Craig, K., Takiyama, Y., Soong, B.-W., Jardim, L. B., Saraiva-Pereira, M. L., Lythgow, K., Morino, H., Maruyama, H., Kawakami, H., Chinnery, P. F. <strong>Pathogenic expansions of the SCA6 locus are associated with a common CACNA1A haplotype across the globe: founder effect or predisposing chromosome?</strong> Europ. J. Hum. Genet. 16: 841-847, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18285829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18285829</a>] [<a href="https://doi.org/10.1038/ejhg.2008.20" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18285829">Craig et al. (2008)</a> identified a common core haplotype carrying the CACNA1A CAG repeat in 45 SCA6 families from different geographic regions, including Europe, Brazil, and Japan. The haplotype was also present in the unaffected father of a proven de novo Japanese patient, suggesting that the shared chromosome predisposes to the CAG repeat expansion at the SCA6 locus. The SCA6 expansion lies immediately downstream of a CpG island, which could act as a cis-acting element predisposing to repeat expansion, as observed for other CAG/CTG repeat diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18285829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#38" class="mim-tip-reference" title="Watase, K., Barrett, C. F., Miyazaki, T., Ishiguro, T., Ishikawa, K., Hu, Y., Unno, T., Sun, Y., Kasai, S., Watanabe, M., Gomez, C. M., Mizusawa, H., Tsien, R. W., Zoghbi, H. Y. <strong>Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant Ca(v)2.1 channels.</strong> Proc. Nat. Acad. Sci. 105: 11987-11992, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18687887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18687887</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18687887[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0804350105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18687887">Watase et al. (2008)</a> found that knockin mice expressing a hyperexpanded polyglutamine (84Q) Cacna1a repeat developed progressive motor impairment consistent with SCA6. Knockin mice with normal 14 CAG or expanded 30 CAG repeats did not show such defects. Electrophysiologic analysis of cerebellar Purkinje cells revealed similar calcium channel current density among the 3 mouse models, although all were decreased compared to wildtype due to decreased channel abundance. Neither voltage sensitivity of activation nor inactivation was altered in the Sca6(84Q) neurons, suggesting that the expanded CAG repeat does not per se affect the intrinsic electrophysiologic properties of the channels. Mice with the hyperexpanded polyglutamine repeat showed cytoplasmic neuronal inclusions, consistent with aggregation of mutant calcium channels. <a href="#38" class="mim-tip-reference" title="Watase, K., Barrett, C. F., Miyazaki, T., Ishiguro, T., Ishikawa, K., Hu, Y., Unno, T., Sun, Y., Kasai, S., Watanabe, M., Gomez, C. M., Mizusawa, H., Tsien, R. W., Zoghbi, H. Y. <strong>Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant Ca(v)2.1 channels.</strong> Proc. Nat. Acad. Sci. 105: 11987-11992, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18687887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18687887</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18687887[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0804350105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18687887">Watase et al. (2008)</a> concluded that the pathogenesis of SCA6 is related to an age-dependent process accompanied by accumulation of mutant CACNA1A channels resulting in a toxic gain-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18687887" 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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Alonso, I., Barros, J., Tuna, A., Coelho, J., Sequeiros, J., Silveira, I., Coutinho, P.
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<strong>Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family.</strong>
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Arch. Neurol. 60: 610-614, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707077/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707077</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12707077" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1001/archneur.60.4.610" target="_blank">Full Text</a>]
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Basri, R., Yabe, I., Soma, H., Sasaki, H.
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<strong>Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families.</strong>
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J. Hum. Genet. 52: 848-855, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17805477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17805477</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17805477" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10038-007-0182-x" target="_blank">Full Text</a>]
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Buttner, N., Geschwind, D., Jen, J. C., Perlman, S., Pulst, S. M., Baloh, R. W.
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<strong>Oculomotor phenotypes in autosomal dominant ataxias.</strong>
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Arch. Neurol. 55: 1353-1357, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9779665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9779665</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9779665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1001/archneur.55.10.1353" target="_blank">Full Text</a>]
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Christova, P., Anderson, J. H., Gomez, C. M.
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<strong>Impaired eye movements in presymptomatic spinocerebellar ataxia type 6.</strong>
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Arch. Neurol. 65: 530-536, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18413478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18413478</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18413478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Molecular epidemiology of spinocerebellar ataxia type 6.</strong>
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Ann. Neurol. 55: 752-755, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15122720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15122720</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15122720" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.20110" target="_blank">Full Text</a>]
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Craig, K., Takiyama, Y., Soong, B.-W., Jardim, L. B., Saraiva-Pereira, M. L., Lythgow, K., Morino, H., Maruyama, H., Kawakami, H., Chinnery, P. F.
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<strong>Pathogenic expansions of the SCA6 locus are associated with a common CACNA1A haplotype across the globe: founder effect or predisposing chromosome?</strong>
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Europ. J. Hum. Genet. 16: 841-847, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18285829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18285829</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18285829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ejhg.2008.20" target="_blank">Full Text</a>]
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Dichgans, M., Schols, L., Herzog, J., Stevanin, G., Weirich-Schwaiger, H., Rouleau, G., Burk, K., Klockgether, T., Zuhlke, C., Laccone, F., Riess, O., Gasser, T.
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<strong>Spinocerebellar ataxia type 6: evidence for a strong founder effect among German families.</strong>
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Neurology 52: 849-852, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10078738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10078738</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10078738" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.52.4.849" target="_blank">Full Text</a>]
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<strong>A patient homozygous for the SCA6 gene with retinitis pigmentosa.</strong>
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[<a href="https://doi.org/10.1034/j.1399-0004.2002.610510.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.410420616" target="_blank">Full Text</a>]
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<strong>Abundant expression and cytoplasmic aggregations of alpha-1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6.</strong>
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[<a href="https://doi.org/10.1093/hmg/8.7.1185" target="_blank">Full Text</a>]
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<strong>Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1.</strong>
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[<a href="https://doi.org/10.1086/514867" target="_blank">Full Text</a>]
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<strong>Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p.</strong>
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[<a href="https://doi.org/10.1093/hmg/6.11.1973" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddl080" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archneur.60.6.858" target="_blank">Full Text</a>]
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<strong>Deficit of heat shock transcription factor 1-heat shock 70 kDa protein 1A axis determines the cell death vulnerability in a model of spinocerebellar ataxia type 6.</strong>
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[<a href="https://doi.org/10.1111/j.1365-2443.2009.01348.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/wnl.57.8.1502" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/6.8.1283" target="_blank">Full Text</a>]
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<strong>SCA6 is caused by moderate CAG expansion in the alpha(1A)-voltage-dependent calcium channel gene.</strong>
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[<a href="https://doi.org/10.1093/hmg/6.8.1289" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000325057.33666.72" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.410420615" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jnnp.64.1.67" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s004390000346" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15480876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15480876</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15480876" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10038-004-0196-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archneur.58.11.1839" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archneur.58.2.300" target="_blank">Full Text</a>]
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<strong>Frequency analysis of autosomal dominant cerebellar ataxias in Taiwanese patients and clinical and molecular characterization of spinocerebellar ataxia type 6.</strong>
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[<a href="https://doi.org/10.1001/archneur.58.7.1105" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/1096-8628(20001211)95:4<351::aid-ajmg10>3.0.co;2-r" target="_blank">Full Text</a>]
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<strong>Dominantly inherited cerebello-olivary atrophy is not due to a mutation at the spinocerebellar ataxia-I, Machado-Joseph disease, or dentato-rubro-pallido-luysian atrophy locus.</strong>
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[<a href="https://doi.org/10.1002/mds.870110210" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s004010050807" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s10038-004-0142-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/302067" target="_blank">Full Text</a>]
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<strong>A Japanese family with spinocerebellar ataxia type 6 which includes three individuals homozygous for an expanded CAG repeat in the SCA6/CACNL1A4 gene.</strong>
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[<a href="https://doi.org/10.1016/s0022-510x(98)00108-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0022-510x(98)00189-0" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.20424" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archneur.61.2.257" target="_blank">Full Text</a>]
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<strong>Predisposing chromosome for spinocerebellar ataxia type 6 (SCA6) in Japanese.</strong>
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J. Med. Genet. 38: 328-333, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11403042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11403042</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11403042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.38.5.328" target="_blank">Full Text</a>]
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<a id="40" class="mim-anchor"></a>
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<a id="Yue1997" class="mim-anchor"></a>
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Yue, Q., Jen, J. C., Nelson, S. F., Baloh, R. W.
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<strong>Progressive ataxia due to a missense mutation in a calcium-channel gene.</strong>
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Am. J. Hum. Genet. 61: 1078-1087, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9345107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9345107</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9345107" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/301613" target="_blank">Full Text</a>]
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<a id="41" class="mim-anchor"></a>
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<a id="Zee1976" class="mim-anchor"></a>
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Zee, D. S., Yee, R. D., Cogan, D. G., Robinson, D. A., Engel, W. K.
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<strong>Ocular motor abnormalities in hereditary cerebellar ataxia.</strong>
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Brain 99: 207-234, 1976.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/990897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">990897</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=990897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/99.2.207" target="_blank">Full Text</a>]
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<a id="42" class="mim-anchor"></a>
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<a id="Zhuchenko1997" class="mim-anchor"></a>
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Zhuchenko, O., Bailey, J., Bonnen, P., Ashizawa, T., Stockton, D. W., Amos, C., Dobyns, W. B., Subramony, S. H., Zoghbi, H. Y., Lee, C. C.
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<strong>Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha(1A)-voltage-dependent calcium channel.</strong>
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Nature Genet. 15: 62-69, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8988170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8988170</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8988170" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng0197-62" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 3/19/2012
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Cassandra L. Kniffin - updated : 8/16/2010<br>Cassandra L. Kniffin - updated : 5/29/2009<br>Cassandra L. Kniffin - updated : 4/13/2009<br>Cassandra L. Kniffin - updated : 1/22/2009<br>Cassandra L. Kniffin - updated : 1/5/2009<br>Cassandra L. Kniffin - updated : 3/6/2008<br>Cassandra L. Kniffin - updated : 5/18/2005<br>Cassandra L. Kniffin - updated : 4/19/2005<br>Cassandra L. Kniffin - updated : 12/15/2004<br>Cassandra L. Kniffin - updated : 7/26/2004<br>Cassandra L. Kniffin - updated : 7/12/2004<br>Victor A. McKusick - updated : 7/9/2004<br>Cassandra L. Kniffin - updated : 5/25/2004<br>Cassandra L. Kniffin - updated : 8/7/2003<br>Cassandra L. Kniffin - updated : 10/28/2002<br>Victor A. McKusick - updated : 9/18/2002<br>Cassandra L. Kniffin - reorganized : 8/22/2002<br>Victor A. McKusick - updated : 12/21/2001<br>Victor A. McKusick - updated : 12/5/2001<br>Michael J. Wright - updated : 6/20/2001<br>Sonja A. Rasmussen - updated : 1/9/2001<br>Victor A. McKusick - updated : 9/13/2000<br>George E. Tiller - updated : 1/18/2000<br>Wilson H. Y. Lo - updated : 8/10/1999<br>Orest Hurko - updated : 6/14/1999<br>Victor A. McKusick - updated : 1/20/1999<br>Victor A. McKusick - updated : 8/17/1998<br>Victor A. McKusick - updated : 7/7/1998<br>Victor A. McKusick - updated : 3/27/1998<br>Victor A. McKusick - updated : 1/13/1998<br>Victor A. McKusick - updated : 11/13/1997<br>Victor A. McKusick - updated : 8/22/1997
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Victor A. McKusick : 6/7/1994
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carol : 12/20/2023
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alopez : 05/14/2019<br>carol : 06/02/2016<br>ckniffin : 3/19/2012<br>alopez : 9/22/2011<br>wwang : 8/24/2010<br>ckniffin : 8/16/2010<br>terry : 12/17/2009<br>wwang : 6/5/2009<br>ckniffin : 5/29/2009<br>wwang : 4/29/2009<br>ckniffin : 4/13/2009<br>wwang : 1/26/2009<br>ckniffin : 1/22/2009<br>wwang : 1/14/2009<br>ckniffin : 1/5/2009<br>wwang : 3/19/2008<br>ckniffin : 3/6/2008<br>ckniffin : 9/22/2005<br>ckniffin : 9/21/2005<br>wwang : 6/1/2005<br>wwang : 5/26/2005<br>ckniffin : 5/18/2005<br>ckniffin : 4/19/2005<br>terry : 2/22/2005<br>tkritzer : 12/15/2004<br>ckniffin : 12/15/2004<br>tkritzer : 7/28/2004<br>ckniffin : 7/26/2004<br>ckniffin : 7/26/2004<br>tkritzer : 7/13/2004<br>ckniffin : 7/12/2004<br>terry : 7/9/2004<br>tkritzer : 5/27/2004<br>ckniffin : 5/25/2004<br>tkritzer : 1/28/2004<br>ckniffin : 1/21/2004<br>ckniffin : 8/7/2003<br>tkritzer : 6/11/2003<br>carol : 6/11/2003<br>tkritzer : 6/11/2003<br>carol : 11/13/2002<br>ckniffin : 10/28/2002<br>carol : 9/18/2002<br>carol : 9/18/2002<br>ckniffin : 9/17/2002<br>ckniffin : 9/6/2002<br>carol : 8/22/2002<br>ckniffin : 8/22/2002<br>tkritzer : 8/9/2002<br>ckniffin : 6/26/2002<br>cwells : 1/10/2002<br>cwells : 1/2/2002<br>terry : 12/21/2001<br>alopez : 12/11/2001<br>terry : 12/5/2001<br>alopez : 6/20/2001<br>mcapotos : 1/9/2001<br>mcapotos : 10/5/2000<br>mcapotos : 9/26/2000<br>terry : 9/13/2000<br>alopez : 1/18/2000<br>carol : 8/10/1999<br>carol : 6/14/1999<br>carol : 1/29/1999<br>terry : 1/20/1999<br>carol : 8/20/1998<br>terry : 8/17/1998<br>carol : 7/13/1998<br>terry : 7/7/1998<br>carol : 6/26/1998<br>terry : 6/3/1998<br>carol : 5/22/1998<br>carol : 5/19/1998<br>alopez : 3/27/1998<br>terry : 3/25/1998<br>alopez : 1/13/1998<br>dholmes : 1/12/1998<br>terry : 11/14/1997<br>terry : 11/13/1997<br>mark : 8/25/1997<br>terry : 8/22/1997<br>alopez : 7/29/1997<br>terry : 7/7/1997<br>jenny : 1/14/1997<br>terry : 1/8/1997<br>mimadm : 5/10/1995<br>carol : 12/7/1994<br>jason : 6/7/1994
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<strong>#</strong> 183086
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SPINOCEREBELLAR ATAXIA 6; SCA6
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<strong>SNOMEDCT:</strong> 715752006;
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<strong>ORPHA:</strong> 98758;
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<strong>DO:</strong> 0050956;
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19p13.13
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Spinocerebellar ataxia 6
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183086
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Autosomal dominant
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3
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CACNA1A
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601011
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<p>A number sign (#) is used with this entry because spinocerebellar ataxia-6 (SCA6) is caused by heterozygous mutation in the CACNA1A gene (601011) on chromosome 19p13.</p><p>The most common mutation is an expanded CAG(n) repeat in exon 47 of the CACNA1A gene (601011.0007). Normal alleles contain 4 to 18 repeats, whereas pathogenic alleles contain 19 to 33 repeats (Li et al., 2009). </p><p>For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).</p>
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<p>Subramony et al. (1996) described a family segregating late-onset progressive cerebellar ataxia with onset of gait difficulties at age 50. There was no pontine atrophy at autopsy nor was there evidence of hypogonadism. The segregation appeared to be autosomal dominant with multiple instances of male-to-male transmission. Direct DNA analysis excluded expansions at the SCA1 (164400), Machado-Joseph (607047), and DRPLA (125370) loci. </p><p>Zhuchenko et al. (1997) reported 8 unrelated families who showed a very similar clinical picture consisting predominantly of mild but slowly progressive cerebellar ataxia of the limbs and gait, dysarthria, nystagmus, and mild vibratory and proprioceptive sensory loss. The disease is insidious and most patients do not realize they are affected initially but do describe a sense of momentary imbalance and 'wooziness' when they make a quick turn or a rapid movement. Typically, it is years after this initial sensation when the patients realize they have developed balance and coordination difficulties. The disease usually progresses over 20 to 30 years, leading to impairment of gait and causing the patient to become wheelchair-bound. In a few older patients, choking has been observed, suggesting involvement of the brainstem. The disease was the cause of death in several members of 2 kindreds. Magnetic resonance imaging (MRI) of the brain in affected individuals demonstrated isolated cerebellar atrophy. By genotype survey, Zhuchenko et al. (1997) found a CAG repeat expansion in the CACNA1A gene (see MOLECULAR GENETICS). </p><p>The clinical and genetic features of 38 genetically confirmed cases of SCA6 from 8 families were described by Ishikawa et al. (1997). Gait ataxia was invariably the initial symptom and was the chief symptom throughout the clinical course. Other symptoms were cerebellar speech, limb ataxia, decreased muscle tonus, and horizontal gaze nystagmus. Tendon reflexes were normal or slightly increased. Extracerebellar symptoms, such as pyramidal or extrapyramidal tract signs, ophthalmoparesis, or decreased sensation, were not seen. None of the patients complained of migraine. Magnetic resonance imaging demonstrated atrophy restricted to the cerebellum. The age at onset ranged from 20 to 66 years, and the average age at onset was 45 years. </p><p>Gomez et al. (1997) described clinical, genetic, neuroimaging, neuropathologic, and quantitative oculomotor studies in 4 kindreds with genotypically confirmed SCA6. The age of onset of ataxia ranged from 24 to 63 years among affected individuals. Radiographically and pathologically, there was selective atrophy of the cerebellum and extensive loss of Purkinje cells in the cerebellar cortex. In addition, clinical and quantitative measurement of extraocular movements demonstrated a characteristic pattern of oculomotor and vestibular abnormalities, including horizontal and vertical nystagmus and an abnormal vestibuloocular reflex. In 2 of the kindreds, they found strong linkage to the CACNL1A4 locus and strong association with the expanded (CAG)n alleles, which were a single size in the 2 kindreds (22 and 23 units). These studies identified a distinct phenotype associated with SCA6, just as SCA7 (164500) is associated with retinopathy and blindness, and SCA2 (183090) is associated with pronounced slowing or loss of saccadic eye movements. One of the families in which the expanded CAG repeat was identified was the family previously reported by Zee et al. (1976). </p><p>Schols et al. (1998) studied 9 German families with spinocerebellar ataxia-6 and found that the phenotype comprised predominantly cerebellar signs in accord with isolated cerebellar atrophy on MRI. Noncerebellar systems were only mildly affected with external ophthalmoplegia, spasticity, peripheral neuropathy, and parkinsonism. Disease onset ranged from 30 to 71 years of age and was significantly later than in other forms of autosomal dominant cerebellar ataxia. Although age at onset correlated inversely with CAG repeat length, other clinical signs and progression rate did not. By comparison with SCA1, SCA2, and SCA3, no clinical or electrophysiologic findings were specific for SCA6. Moreover, the molecular defect could not be predicted from clinical investigations. </p><p>Fukutake et al. (2002) described a 55-year-old man, the offspring of first-cousin parents, who presented not only with cerebellar ataxia and vertical antidirectional nystagmus but also with retinitis pigmentosa. The numbers of CAG repeats in the expanded alleles of the SCA6 gene were 21 on each chromosome. The retinal degeneration was thought to be secondary to a genetic disorder of either autosomal or X-linked recessive inheritance rather than SCA6. The association of retinitis pigmentosa with spinocerebellar ataxia is most characteristic of SCA7 (164500). Both parents had staggering gait and slurred speech late in life, but were not available for study. </p><p>In 7 SCA6 patients, van de Warrenburg et al. (2004) found no significant electrophysiologic evidence of peripheral nerve involvement. </p><p><strong><em>Pathologic Findings</em></strong></p><p>
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Tsuchiya et al. (1998) described a Japanese family with 2 affected sisters and an affected father. The proband developed gait disturbance at age 62 years and died at age 67 years due to subarachnoid hemorrhage. Neuropathologic examination showed severe loss of Purkinje cells in the cerebellum, predominantly in the dorsal vermis, and absence of neuronal loss in the inferior olives. The younger sister developed gait disturbance also at age 62 years. Neuroimaging at the age of 66 years showed cerebellar atrophy, predominantly in the vermis. Tsuchiya et al. (1998) performed a neuropathologic review of Japanese autopsy cases of autosomal dominant cortical cerebellar atrophy and found 2 patterns in the distribution of cerebellar cortical lesions. The distribution of cerebellar cortical lesions in genetically confirmed Japanese patients with SCA6 was more prominent in the vermis than in the hemisphere. </p><p>Takahashi et al. (1998) described a family with dominantly inherited ataxia of late adult onset with affected individuals in 4 generations. Expansion of a CAG repeat in the CACNA1A gene was identified at autopsy in 1 patient, a 65-year-old woman with a disease duration of 11 years. In this patient, pathologic changes were confined to the cerebellar cortex and inferior olivary complex. The cerebellar cortex showed severe loss of Purkinje cells with proliferation of Bergmann glia, more pronounced in the superior parts of the vermis and hemispheres. In the inferior olivary complex, a reduced neuronal cell population, which could be interpreted as a change secondary to the cerebellar cortical lesion, was evident. They concluded that the pathologic phenotype of SCA6 is cerebelloolivary atrophy, or more strictly cerebellar cortical atrophy. </p>
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<h4>
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<span class="mim-font">
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<strong>Other Features</strong>
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</h4>
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<p>Soong et al. (2001) performed positron emission tomography using labeled glucose on 7 patients with SCA6 and 7 healthy controls to elucidate metabolic features of SCA6. They found significant hypometabolism in the patients with SCA6, ranging from 63 to 78% that of controls, in the brainstem, cerebellar hemisphere, basal ganglia, and various areas of the cortex. None of the patients manifested symptoms referable to the basal ganglia or cerebral cortices. Although Soong et al. (2001) postulated that the differences may be due to subclinical neuronal cell dysfunction, variation in regional blood flow, or metabolic dysfunction in structurally intact neurons, they suggested that the findings may indicate that SCA6 is not a purely cerebellar syndrome. </p><p>Christova et al. (2008) observed abnormal ocular motor anomalies in 4 presymptomatic SCA6 patients with CACNA1A mutations. Two patients had a low-amplitude horizontal gaze-evoked nystagmus, 1 of whom had a significantly decreased eye velocity for upward saccades and an abnormal frequency of square-wave jerks. Another had abnormal square-wave jerks, and a fourth had a reduced gain for pursuit tracking. Multivariate analysis discriminated the presymptomatic patients as a group from healthy controls and 5 manifesting SCA6 patients. Christova et al. (2008) suggested that early functional oculomotor impairments in SCA6 are caused by cellular dysfunction and/or loss in the posterior cerebellar vermis and flocculus. </p>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</h4>
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<p>Ishikawa et al. (1997) carried out genomewide linkage analysis in 15 Japanese families with autosomal dominant pure cerebellar ataxia (ADPCA). Evidence for linkage to chromosome 19p markers was found in 8 families, all of whom showed expansion of a CAG repeat in the CACNA1A gene, and combined multipoint analysis refined the candidate region to a 13.3-cM interval in 19p13.2-p13.1. 6 families were excluded for this region and 1 family was inconclusive. </p>
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<h4>
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<span class="mim-font">
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<strong>Pathogenesis</strong>
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</h4>
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<span class="mim-text-font">
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<p>Expansion of repeat sequences involving the trinucleotides CAG, CTG, CGG, or GAA is the primary cause of several dominantly inherited neurologic disorders. Among them, CAG repeat expansions have been associated with Huntington disease (HD; 143100), X-linked spinobulbar muscular atrophy (313200), and several spinocerebellar ataxias. Zhuchenko et al. (1997) noted that the CAG repeat arrays in these diseases are located in the coding region of the involved gene and are translated into polyglutamine tracts in the protein product. It is postulated that an expansion of the polyglutamine tract produces a gain of function in the protein product in each disease, accounting for the dominant inheritance. </p><p>Ishikawa et al. (1999) used RT-PCR and in situ hybridization to demonstrate that the calcium channel mRNA/protein containing the CAG repeat/polyglutamine tract is most intensely expressed in Purkinje cells of normal human brains. In SCA6 brains, numerous oval or rod-shaped aggregates were seen exclusively in the cytoplasm of Purkinje cells. These cytoplasmic inclusions were not ubiquitinated, which contrasts with the neuronal intranuclear inclusions of other CAG repeat/polyglutamine diseases. In cultured cells, formation of perinuclear aggregates of the channel protein and apoptotic cell death were seen when transfected with full-length CACNA1A coding an expanded polyglutamine tract. The authors concluded that the mechanism of neurodegeneration in SCA6 is associated with cytoplasmic aggregations of the alpha-1A calcium channel protein caused by a small CAG repeat/polyglutamine expansion in CACNA1A. </p><p>Kordasiewicz et al. (2006) found that a 75-kD C-terminal fragment of CACNA1A, which is the location of the polyglutamine tract expanded in SCA6, is cleaved from the full-length protein and translocated to the nucleus, where it is toxic to cells when in the expanded state. The polyglutamine-mediated cell toxicity was dependent on nuclear localization, suggesting that specific processing and localization of the mutant protein is involved in the pathogenesis of SCA6. </p><p>Li et al. (2009) confirmed that C-terminal fragments of CACNA1A localized predominantly to the nucleus of HEK293 cells where they existed as speckle-like structures resembling promyelocytic leukemia nuclear bodies (PMLNBs). HEK293 cells expressing an expanded (24 CAG repeats) C-terminal end of CACNA1A showed decreased viability when exposed to toxic cadmium compared to cells with nonexpanded (13 CAG) repeats. However, there were no differences in viability under normal culture conditions. Cadmium treatment also disrupted the PMLNBs and enhanced aggregation of C-terminal CACNA1A fragments, particularly in CAG-expanded cells. Immunocytochemical studies showed that cadmium-induced death was caspase-3 (CASP3; 600636)-dependent, indicating apoptosis. Gene expression studies showed downregulation of the HSF1 (140580)-HSPA1A (140550) axis as an event in 24-CAG repeat cells that appeared to be critical for cellular toxicity. The findings were consistent with SCA6 pathogenesis being related to polyglutamine diseases. </p>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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<p>The transmission pattern of SCA6 in the families reported by Zhuchenko et al. (1997) was consistent with autosomal dominant inheritance. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>Zhuchenko et al. (1997) performed a genotyping survey using polymorphic CAG repeats and DNA samples from patients with late-onset neurogenic diseases. In the course of these studies they found an expansion of a CAG repeat in the human alpha-1A-voltage-dependent Ca(2+) channel gene (601011.0007), which maps to 19p13. They identified 6 isoforms of the human alpha-1A calcium channel subunit. The CAG repeat was within the open reading frame and was predicted to encode glutamine in 3 of the isoforms. In 8 families, the CAG repeat expansion of the Ca(2+) channel gene was the mutation mechanism for SCA6. One of the families had been reported by Subramony et al. (1996). </p><p>Analysis of CAG repeat expansion in the CACNL1A4 gene by Ishikawa et al. (1997) revealed expansion in 8 of 15 Japanese families with autosomal dominant cerebellar ataxia; all affected individuals had larger alleles (range of CAG repeats 21 to 25), compared with alleles observed in neurologically normal Japanese (range 5 to 20 repeats). </p><p>Takiyama et al. (1998) studied a Japanese family that included 13 persons with SCA6 in 5 generations. Molecular testing revealed that the patients carried the smallest known expanded CAG repeat (21 repeat units). The clinical features of these patients included predominantly cerebellar ataxia with onset late in adult life and a very slowly progressive course. In addition, this SCA6 family showed some characteristic clinical and genetic features, including (1) apparent lack of genetic anticipation, with an intergenerationally stable CAG repeat size, and (2) down-beat nystagmus and diabetes mellitus in some of the SCA6 patients. They identified 3 individuals homozygous for an expanded CAG repeat (21/21) in the CACNL1A4 gene; 2 were symptomatic and 1 was asymptomatic at age 50 years. There was no apparent difference in clinical phenotype between the homozygotes and the heterozygotes. </p><p>Fukutake et al. (2002) stated that 11 patients with genetically verified SCA6 who were homozygous or compound heterozygous for (CAG)n repeats in the CACNA1A gene (601011.0007) had previously been reported. </p><p>In a family in which multiple members had severe progressive cerebellar ataxia involving the trunk, extremities, and speech, Yue et al. (1997) identified a 1152G-A transition in exon 6 of the CACNA1A gene, resulting in a gly293-to-arg substitution (G293R; 601011.0009). The CAG(n) repeat expansion associated with SCA6 was not present in any family member. </p><p>In a large Portuguese family in which 17 patients over 4 generations were affected with hemiplegic migraine and/or progressive SCA6, Alonso et al. (2003) found that all patients shared a common haplotype and carried an arg583-to-gln mutation in the CACNA1A gene (R583Q; 601011.0018). </p><p><strong><em>Genetic Anticipation</em></strong></p><p>
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In his studies of families with SCA6, Zhuchenko et al. (1997) noted that there seemed to be a correlation between the repeat number and earlier onset of the disorder. Matsuyama et al. (1997) analyzed 60 SCA6 individuals from 39 independent Japanese SCA6 families and found that the CAG repeat length in the CACNL1A4 gene was inversely correlated with age of onset. SCA6 chromosomes contained 21 to 30 repeat units, whereas normal chromosomes displayed 6 to 17 repeats. There was no overlap between the normal and affected CAG repeat number. Anticipation was observed clinically in all 8 parent-child pairs examined; the mean age of onset was significantly lower (P = 0.0042) in children than in parents. However, a parent-child analysis showed an increase in the expansion of CAG repeats only in 1 pair and no diminution in any affected cases. The results suggested that factors other than CAG repeats may produce the clinical anticipation. A homozygotic case could not demonstrate unequivocal gene dosage effect on the age of onset. </p><p>In the 8 families with SCA6 reported by Ishikawa et al. (1997), inverse correlation between the CAG-repeat number and the age of onset was found in affected individuals with expansion. The number of CAG repeats in expanded chromosomes was completely stable within each family, which was consistent with the fact that anticipation was not statistically proven in these SCA6 families. </p><p>Riess et al. (1997) observed the trinucleotide expansion in 4 ataxia patients without obvious family history of the disease, indicating the necessity to search for the SCA6 (CAG)n expansion even in sporadic patients. In their series of 32 patients, onset was usually late and the (CAG)n stretch varied between 22 and 28 trinucleotide units, the shortest trinucleotide repeat expansion causing spinocerebellar ataxia. Analyzing 248 apparently healthy octogenarians, Riess et al. (1997) found 1 allele of 18 repeats, the longest normal CAG repeat in the CACNL1A4 gene reported to that time. They could demonstrate no repeat instability of the expanded allele on transmission and no repeat instability was found for the normal allele in 431 meioses in the CEPH families. </p><p>Mariotti et al. (2001) described an Italian family in which 1 member carried a fully expanded SCA6 allele with 26 CAG repeats, whereas the other affected family member was homozygous for an intermediate allele of 19 CAG repeats. Three family members, heterozygous for the intermediate allele, were clinically unaffected. The findings demonstrated a dose-dependent pathogenic effect of an intermediate CAG expansion in the SCA6 gene. </p><p>Takahashi et al. (2004) retrospectively analyzed 140 patients with SCA6. They observed an inverse correlation between the age at onset and the length of the expanded allele, and also between the age at onset and the sum of CAG repeats in the normal and the expanded alleles. The ages at onset of 4 homozygous patients correlated better with the sum of CAG repeats in both alleles than with the expanded allele calculated from heterozygous SCA6 patients. Clinically, unsteadiness of gait was the main initial symptom, followed by vertigo and oscillopsia, and cerebellar signs were detected in nearly 100% of the patients. In contrast, extracerebellar signs were relatively mild and infrequent. Neuro-otologic examination performed in 22 patients suggested that the abnormalities of ocular movements were purely cerebellar in nature. There was a close relationship between down-beat positioning nystagmus and positioning vertigo, which became more common in the later stage. Takahashi et al. (2004) concluded that total number of CAG repeat units in both alleles is a good parameter for assessment of age at onset in SCA6, including in homozygous patients. In addition, clinical and neuro-otologic examination suggested that SCA6 is a disease with predominantly cerebellar dysfunction. </p><p>Van de Warrenburg et al. (2005) applied statistical analysis to examine the relationship between age at onset and number of expanded triplet repeats from a Dutch-French cohort of 802 patients with SCA1 (138 patients), SCA2 (166 patients), SCA3 (342 patients), SCA6 (53 patients), and SCA7 (103 patients). The size of the expanded repeat explained 66 to 75% of the variance in age at onset for SCA1, SCA2, and SCA7, but less than 50% for SCA3 and SCA6. The relation between age at onset and CAG repeat was similar for all groups except for SCA2, suggesting that the polyglutamine repeat in the ataxin-2 protein exerts its pathologic effect in a different way. A contribution of the nonexpanded allele to age at onset was observed for only SCA1 and SCA6. Van de Warrenburg et al. (2005) acknowledged that their results were purely mathematical, but suggested that they reflected biologic variations among the diseases. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Schols et al. (1997) compared clinical, electrophysiologic, and MRI findings to identify phenotypic characteristics of genetically defined SCA subtypes. Slow saccades, hyporeflexia, myoclonus, and action tremor suggested SCA2. SCA3 (109150) patients frequently developed diplopia, severe spasticity or pronounced peripheral neuropathy, and impaired temperature discrimination, apart from ataxia. SCA6 presented with a predominantly cerebellar syndrome, and patients often had onset after 55 years of age. SCA1 (164400) was characterized by markedly prolonged peripheral and central motor conduction times in motor evoked potentials. MRI scans showed pontine and cerebellar atrophy in SCA1 and SCA2. In SCA3, enlargement of the fourth ventricle was the main sequel of atrophy. SCA6 presented with pure cerebellar atrophy on MRI. Overlap among the 4 SCA subtypes was broad, however. </p><p>In an investigation of oculomotor function, Buttner et al. (1998) found that all 3 patients with SCA1, all 7 patients with SCA3, and all 5 patients with SCA6 had gaze-evoked nystagmus. Three of 5 patients with SCA2 did not have gaze-evoked nystagmus, perhaps because they could not generate corrective fast components. Rebound nystagmus occurred in all SCA3 patients, 33% of SCA1 patients, 40% of SCA6 patients, and none of SCA2. Spontaneous downbeat nystagmus only occurred in SCA6. Peak saccade velocity was decreased in 100% of patients with SCA2, 1 patient with SCA1, and no patients with SCA3 or SCA6. Saccade hypermetria was found in all types, but was most common in SCA3. </p><p>Using an analysis of covariance and multivariate models to examine symptom severity in 526 patients with SCA1, SCA2, SCA3, or SCA6, Schmitz-Hubsch et al. (2008) found that repeat length of the expanded allele, age at onset, and disease duration explained 60.4% of the ataxia score in SCA1, 45.4% in SCA2, 46.8% in SCA3. However, only age at onset and disease duration appeared to explain 33.7% of the score in SCA6. Similar findings were obtained for nonataxic symptoms. The study suggested that SCA1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Heterogeneity</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>In a family initially classified as autosomal dominant cerebellar ataxia of unknown type, Jodice et al. (1997) found an intergenerational allele size change in the CACNA1A gene, showing that a (CAG)20 allele (601011.0008) was associated with the phenotype of episodic ataxia type 2 (EA2; 108500) and a (CAG)25 allele with progressive cerebellar ataxia. These results suggested that EA2 and SCA6 are the same disorder with a high phenotypic variability, at least partly related to the number of repeats, and suggested that the small expansions may not be as stable as previously reported. </p><p>Sinke et al. (2001) described a study of 24 Dutch families with SCA6. Clinical analysis identified SCA6 as a late-onset ataxia in which eye movement abnormalities are prominent and consistent early manifestations. Some patients had ataxia combined with episodic headaches or nausea, suggesting an overlap among SCA6, episodic ataxia type 2, and familial hemiplegic migraine (141500). </p><p>In a large Portuguese family in which 17 patients over 4 generations were affected with hemiplegic migraine and/or progressive SCA6, Alonso et al. (2003) found that all patients shared a common haplotype and carried an arg583-to-gln mutation in the CACNA1A gene (R583Q; 601011.0018). Four patients, all under the age of 18 years, had only hemiplegic migraine, 8 patients had isolated progressive cerebellar ataxia, and 5 patients had both hemiplegic migraine and cerebellar ataxia. Several patients reported symptoms triggered by minor head trauma. Alonso et al. (2003) suggested that EA2, SCA6, and familial hemiplegic migraine are not only allelic disorders, but may be the same disorder with great phenotypic variability. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Riess et al. (1997) found that the SCA6 mutation accounts for approximately 10% of autosomal dominant SCA in Germany. </p><p>Studying 77 German families with autosomal dominant cerebellar ataxia of SCA types 1, 2, 3, and 6, Schols et al. (1997) found that the SCA1 mutation accounted for 9%, SCA2 for 10%, SCA3 for 42%, and SCA6 for 22%. There was no family history of ataxia in 7 of 27 SCA6 patients. Age at onset correlated inversely with repeat length in all subtypes, yet the average effect of 1 CAG unit on age of onset was different for each SCA subtype. Schols et al. (1998) investigated the SCA6 mutation (expanded repeat in the CACNA1A gene) in 69 German families with autosomal dominant cerebellar ataxia and 61 patients with idiopathic sporadic cerebellar ataxia. The expanded CAG repeat was found in 9 of 69 families, as well as in 4 patients with sporadic disease. Schols et al. (1998) noted that in Germany, SCA6 accounts for about 13% of families with autosomal dominant cerebellar ataxia. However, up to 30% of SCA6 kindreds may be misdiagnosed clinically as sporadic disease due to late manifestation in apparently healthy parents. Genetic testing was therefore recommended for the SCA6 mutation also in patients with putative sporadic ataxia. In a study of apparently idiopathic sporadic cerebellar ataxia involving 124 patients, Schols et al. (2000) found the SCA6 mutation in 9 patients with disease onset between 47 and 68 years of age. </p><p>Using an intragenic marker, D19S1150, and 2 markers (DS19S221 and DS19S226) bracketing 3 cM on either side, Dichgans et al. (1999) found a common haplotype in 7 of 12 German families segregating SCA6. This finding, as well as a clustering of the families from Northrhine-Westfalia, strongly suggests a founder effect. </p><p>From their study of 15 families with autosomal dominant cerebellar ataxia, Ishikawa et al. (1997) concluded that more than half of Japanese cases of ADPCA map to 19p and are strongly associated with a mild CAG expansion in the SCA6/CACNL1A4 gene. </p><p>Watanabe et al. (1998) investigated 101 kindreds with spinocerebellar ataxias from the central Honshu island of Japan, using a molecular diagnostic approach with amplification of the CAG trinucleotide repeat of the causative genes. Machado-Joseph disease (109150) was the most prevalent (33.7%) form, followed by dentatorubral-pallidoluysian atrophy (125370; 19.8%), SCA6 (5.9%), and SCA2 (5.9%). All 7 SCA6 patients had expanded alleles of the CACNL1A4 gene and signs of a pure cerebellar syndrome. </p><p>Among 202 Japanese and 177 Caucasian families with autosomal dominant SCA, Takano et al. (1998) found that the prevalence of SCA6 was significantly higher in the Japanese population (11%) compared to Caucasian population (5%). This corresponded to higher frequencies of large normal CACNA1A CAG repeat alleles (greater than 13 repeats) in Japanese controls compared to Caucasian controls. The findings suggested that large normal alleles contribute to the generation of expanded alleles that lead to dominant SCA. </p><p>Yabe et al. (2001) studied 21 Japanese families with SCA6 and found one of 2 haplotypes in each family. They suggested a mechanism by which the second haplotype could have arisen from a single common haplotype, and that therefore there was evidence of a founder effect in SCA6 families in Japan. </p><p>Storey et al. (2000) examined the frequency of mutations for SCA types 1, 2, 3, 6, and 7 in southeastern Australia. Of 63 pedigrees or individuals with positive tests, 30% had SCA1, 15% had SCA2, 22% had SCA3, 30% had SCA6, and 3% had SCA7. Ethnic origin was of importance in determining SCA type: 4 of 9 SCA2 index cases were of Italian origin, and 4 of 14 SCA3 index cases were of Chinese origin. </p><p>Sinke et al. (2001) determined that SCA6 accounted for approximately 11% of all Dutch families with autosomal dominant cerebellar ataxia. </p><p>Among 74 Taiwanese families with autosomal dominant cerebellar ataxia and 49 Taiwanese patients with sporadic ataxia, Soong et al. (2001) determined that SCA6 accounted for 10.8% of the familial cases and 4.1% of the sporadic cases. The prevalence of SCA3 was 47.3%, followed by SCA2 (10.8%), SCA1 (5.4%), SCA7 (2.7%), and DRPLA (1.4%). In the families with SCA6, there was significant anticipation in the absence of genetic instability. The same allele of intragenic marker D19S1150 was found in 70% of the SCA6 patients, suggesting a founder effect. </p><p>Of 253 unrelated Korean patients with progressive cerebellar ataxia, Lee et al. (2003) identified 52 (20.6%) with expanded CAG repeats. The most frequent SCA type was SCA2 (33%), followed by SCA3 (29%), SCA6 (19%), SCA1 (12%), and SCA7 (8%). There were characteristic clinical features, such as hypotonia and optic atrophy for SCA1, hyporeflexia for SCA2, nystagmus, bulging eye, and dystonia for SCA3, and macular degeneration for SCA7. </p><p>By haplotype analysis of 12 Dutch SCA6 families confirmed by genotype, Verbeek et al. (2004) found that 8 families (approximately 70%) shared a region between markers D19S1165 and D19S840, including the SCA6 gene, which was not observed in 80 control chromosomes. Two additional SCA6 families shared an extended haplotype. Genealogic research showed that most of the families were clustered in North Holland. The authors noted that mutation in the SCA6 gene occurs in 23.4% of the Dutch autosomal dominant cerebellar ataxia population. Similar haplotype results were found for SCA3. </p><p>In a population-based study in Northeastern England, Craig et al. (2004) estimated that the number of people with or at risk for SCA6 was at least 5.21/100,000, or 1 in 19,210. Haplotype analysis suggested a founder effect, and 56% of affected individuals had an identical CAG repeat length (21 repeats). The clinical phenotype of this group was homogeneous. </p><p>Shimizu et al. (2004) estimated the prevalence of SCA in the Nagano prefecture of Japan to be at least 22 per 100,000. Thirty-one of 86 families (36%) were positive for SCA disease-causing repeat expansions: SCA6 was the most common form (19%), followed by DRPLA (10%), SCA3 (3%), SCA1 (2%), and SCA2 (1%). The authors noted that the prevalence of SCA3 was lower compared to other regions in Japan, and that the number of genetically undetermined SCA families in Nagano was much higher than in other regions. Nagano is the central district of the main island of Japan, located in a mountainous area surrounded by the Japanese Alps. The restricted geography suggested that founder effects may have contributed to the high frequency of genetically undetermined ADCA families. </p><p>Among 113 Japanese families from the island of Hokkaido with autosomal dominant SCA, Basri et al. (2007) found that SCA6 was the most common form of the disorder, identified in 35 (31%) families. Thirty (27%) families had SCA3, 11 (10%) had SCA1, 5 (4%) had SCA2, 5 (4%) had DRPLA, 10 (9%) had 16q22-linked SCA (117210), and 1 (1%) had SCA14 (605361). The specific disorder could not be identified in 16 (14%) families. </p><p>Craig et al. (2008) identified a common core haplotype carrying the CACNA1A CAG repeat in 45 SCA6 families from different geographic regions, including Europe, Brazil, and Japan. The haplotype was also present in the unaffected father of a proven de novo Japanese patient, suggesting that the shared chromosome predisposes to the CAG repeat expansion at the SCA6 locus. The SCA6 expansion lies immediately downstream of a CpG island, which could act as a cis-acting element predisposing to repeat expansion, as observed for other CAG/CTG repeat diseases. </p>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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<span class="mim-text-font">
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<p>Watase et al. (2008) found that knockin mice expressing a hyperexpanded polyglutamine (84Q) Cacna1a repeat developed progressive motor impairment consistent with SCA6. Knockin mice with normal 14 CAG or expanded 30 CAG repeats did not show such defects. Electrophysiologic analysis of cerebellar Purkinje cells revealed similar calcium channel current density among the 3 mouse models, although all were decreased compared to wildtype due to decreased channel abundance. Neither voltage sensitivity of activation nor inactivation was altered in the Sca6(84Q) neurons, suggesting that the expanded CAG repeat does not per se affect the intrinsic electrophysiologic properties of the channels. Mice with the hyperexpanded polyglutamine repeat showed cytoplasmic neuronal inclusions, consistent with aggregation of mutant calcium channels. Watase et al. (2008) concluded that the pathogenesis of SCA6 is related to an age-dependent process accompanied by accumulation of mutant CACNA1A channels resulting in a toxic gain-of-function effect. </p>
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<div>
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Cassandra L. Kniffin - updated : 3/19/2012<br>Cassandra L. Kniffin - updated : 8/16/2010<br>Cassandra L. Kniffin - updated : 5/29/2009<br>Cassandra L. Kniffin - updated : 4/13/2009<br>Cassandra L. Kniffin - updated : 1/22/2009<br>Cassandra L. Kniffin - updated : 1/5/2009<br>Cassandra L. Kniffin - updated : 3/6/2008<br>Cassandra L. Kniffin - updated : 5/18/2005<br>Cassandra L. Kniffin - updated : 4/19/2005<br>Cassandra L. Kniffin - updated : 12/15/2004<br>Cassandra L. Kniffin - updated : 7/26/2004<br>Cassandra L. Kniffin - updated : 7/12/2004<br>Victor A. McKusick - updated : 7/9/2004<br>Cassandra L. Kniffin - updated : 5/25/2004<br>Cassandra L. Kniffin - updated : 8/7/2003<br>Cassandra L. Kniffin - updated : 10/28/2002<br>Victor A. McKusick - updated : 9/18/2002<br>Cassandra L. Kniffin - reorganized : 8/22/2002<br>Victor A. McKusick - updated : 12/21/2001<br>Victor A. McKusick - updated : 12/5/2001<br>Michael J. Wright - updated : 6/20/2001<br>Sonja A. Rasmussen - updated : 1/9/2001<br>Victor A. McKusick - updated : 9/13/2000<br>George E. Tiller - updated : 1/18/2000<br>Wilson H. Y. Lo - updated : 8/10/1999<br>Orest Hurko - updated : 6/14/1999<br>Victor A. McKusick - updated : 1/20/1999<br>Victor A. McKusick - updated : 8/17/1998<br>Victor A. McKusick - updated : 7/7/1998<br>Victor A. McKusick - updated : 3/27/1998<br>Victor A. McKusick - updated : 1/13/1998<br>Victor A. McKusick - updated : 11/13/1997<br>Victor A. McKusick - updated : 8/22/1997
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