3894 lines
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Entry
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- *604490 - SACSIN; SACS
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*604490</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular 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="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604490">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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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>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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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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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000151835;t=ENST00000382292" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=26278" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=604490" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" 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.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000151835;t=ENST00000382292" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001278055,NM_014363,XM_005266338,XM_011535039,XM_017020539,XM_024449337,XM_047430254,XM_047430255,XM_047430256,XM_047430257,XM_047430258,XM_047430259,XM_047430260,XM_047430261,XM_047430262,XM_047430263" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_014363" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=604490" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" 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://hprd.org/summary?hprd_id=05135&isoform_id=05135_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/SACS" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/3882181,6907042,21748792,34365253,51476565,119628728,122066060,163659918,491227401,530402261,767977571,1034584280,1370463777,2217294105,2217294109,2217294112,2217294115,2217294117,2217294119,2217294121,2217294123,2217294125,2217294127,2462536861,2462536863,2462536865,2462536867,2462536869,2462536871,2462536873,2462536875,2462536877,2462536879,2462536881,2462536883,2462536885,2462536887" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q9NZJ4" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" 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="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" 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="http://biogps.org/#goto=genereport&id=26278" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000151835;t=ENST00000382292" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=SACS" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=SACS" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+26278" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/SACS" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:26278" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/26278" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr13&hgg_gene=ENST00000382292.9&hgg_start=23328830&hgg_end=23433702&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" 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="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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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse 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://search.clinicalgenome.org/kb/gene-dosage/HGNC:10519" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/sacs" 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=604490[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>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604490[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/SACS/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000151835" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=SACS" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=SACS" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SACS" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.medgen.mcgill.ca/SACSIN/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SACS&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA34927" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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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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</span>
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</div>
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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/gene/HGNC:10519" 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="https://www.mousephenotype.org/data/genes/MGI:1354724" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/SACS#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:1354724" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/26278/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002780/" 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://www.orthodb.org/?ncbi=26278" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-110411-146" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" 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="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" 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://reactome.org/content/query?q=SACS&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</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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</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> 702445005<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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604490
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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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SACSIN; SACS
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</span>
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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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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SACS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SACS</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/13/31?start=-3&limit=10&highlight=31">13q12.12</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr13:23328830-23433702&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">13:23,328,830-23,433,702</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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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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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/13/31?start=-3&limit=10&highlight=31">
|
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13q12.12
|
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</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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Spastic ataxia, Charlevoix-Saguenay type
|
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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/270550"> 270550 </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 recessive">AR</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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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/604490" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/604490" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</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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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<p>The SACS gene encodes sacsin, a protein believed to integrate the ubiquitin-proteasome system and Hsp70 chaperone machinery and implicated in the processing of ataxin-1 (ATXN1; <a href="/entry/601556">601556</a>) (<a href="#9" class="mim-tip-reference" title="Parfitt, D. A., Michael, G. J., Vermeulen, E. G. M., Prodromou, N. V., Webb, T. R., Gallo, J.-M., Cheetham, M. E., Nicoll, W. S., Blatch, G. L., Chapple, J. P. <strong>The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1.</strong> Hum. Molec. Genet. 18: 1556-1565, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208651[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/10.1093/hmg/ddp067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208651">Parfitt et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19208651" 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="#5" class="mim-tip-reference" title="Engert, J. C., Berube, P., Mercier, J., Dore, C., Lepage, P., Ge, B., Bouchard, J.-P., Mathieu, J., Melancon, S. B., Schalling, M., Lander, E. S., Morgan, K., Hudson, T. J., Richter, A. <strong>ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF.</strong> Nature Genet. 24: 120-125, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655055</a>] [<a href="https://doi.org/10.1038/72769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655055">Engert et al. (2000)</a> reported the cloning of the SACS gene, which encodes the protein sacsin. The open reading frame is conserved in human and mouse. Sequence analysis of the 3,829-amino acid SACS protein predicted 2 leucine zippers, 3 coiled-coils, and 7 nuclear localization signals. The C-terminal portion of the protein contains a hydrophilic domain and a DnaJ motif (see <a href="/entry/604189">604189</a>). The putative protein contains 3 large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana open reading frame. The presence of heat-shock domains suggested a function for sacsin in chaperone-mediated protein folding. Northern blot analysis detected SACS expression as a 12.8-kb transcript in fibroblasts, brain, skeletal muscle, and at low levels in pancreas. In situ hybridization to human, monkey, and rat brain tissue showed intense labeling in all areas of the central nervous system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655055" 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>With the finding of 8 additional exons, the SACS gene is predicted to encode a 4,579-amino acid protein (<a href="#8" class="mim-tip-reference" title="Ouyang, Y., Takiyama, Y., Sakoe, K., Shimazaki, H., Ogawa, T., Nagano, S., Yamamoto, Y., Nakano, I. <strong>Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon.</strong> Neurology 66: 1103-1104, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606928</a>] [<a href="https://doi.org/10.1212/01.wnl.0000204300.94261.ea" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16606928">Ouyang et al., 2006</a>). <a href="#9" class="mim-tip-reference" title="Parfitt, D. A., Michael, G. J., Vermeulen, E. G. M., Prodromou, N. V., Webb, T. R., Gallo, J.-M., Cheetham, M. E., Nicoll, W. S., Blatch, G. L., Chapple, J. P. <strong>The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1.</strong> Hum. Molec. Genet. 18: 1556-1565, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208651[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/10.1093/hmg/ddp067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208651">Parfitt et al. (2009)</a> identified an ubiquitin-like (UBL) domain in the N terminus of sacsin that interacted with the proteasome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19208651+16606928" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Romano, A., Tessa, A., Barca, A., Fattori, F., de Leva, M. F., Terracciano, A., Storelli, C., Santorelli, F. M., Verri, T. <strong>Comparative analysis and functional mapping of SACS mutations reveal novel insights into sacsin repeated architecture.</strong> Hum. Mutat. 34: 525-537, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23280630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23280630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23280630[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/10.1002/humu.22269" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23280630">Romano et al. (2013)</a> characterized the 3 sacsin repeating region (SRR) supradomains and determined that they are much larger (1,100 residues or more) than previously reported. These regions are organized into discrete subrepeats. The large repeated regions were termed 'Sacsin Internal RePeaTs' (SIRPT1, SIRPT2, and SIRPT3), and the subrepeats sr1, sr2, sr3, and srX. Comparative analysis of vertebrate sacsins showed that these regions are highly conserved among vertebrates. Fine positional mapping of a set of human SACS mutations revealed that sr1, sr2, sr3, and srX are functional. In addition, the position of the pathogenic mutations in sr1, sr2, sr3, and srX appeared to be related to the severity of the clinical phenotype, as assessed by defining a severity scoring system. These results suggested that the relative position of mutations in subrepeats will variably influence sacsin dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23280630" 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="#5" class="mim-tip-reference" title="Engert, J. C., Berube, P., Mercier, J., Dore, C., Lepage, P., Ge, B., Bouchard, J.-P., Mathieu, J., Melancon, S. B., Schalling, M., Lander, E. S., Morgan, K., Hudson, T. J., Richter, A. <strong>ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF.</strong> Nature Genet. 24: 120-125, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655055</a>] [<a href="https://doi.org/10.1038/72769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655055">Engert et al. (2000)</a> found that the 11,487-bp open reading frame of SACS is encoded by a single gigantic exon spanning 12,794 bp. This exon was the largest to be identified in any vertebrate organism. The largest exons previously reported were those of the X inactivation-specific transcript (XIST; <a href="/entry/314670">314670</a>), which does not encode a protein, 11,363 bp; and an exon of the mucin gene (MUC5B; <a href="/entry/600770">600770</a>), measuring 10,713 bp. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655055" 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>Eight novel exons located upstream of the gigantic exon have been identified, bringing the total number of exons in the SACS gene to 9. The gigantic exon is referred to as exon 9 (<a href="#8" class="mim-tip-reference" title="Ouyang, Y., Takiyama, Y., Sakoe, K., Shimazaki, H., Ogawa, T., Nagano, S., Yamamoto, Y., Nakano, I. <strong>Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon.</strong> Neurology 66: 1103-1104, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606928</a>] [<a href="https://doi.org/10.1212/01.wnl.0000204300.94261.ea" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16606928">Ouyang et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16606928" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Baets, J., Deconinck, T., Smets, K., Goossens, D., Van den Bergh, P., Dahan, K., Schmedding, E., Santens, P., Rasic, V. M., Van Damme, P., Robberecht, W., De Meirleir, L., Michielsens, B., Del-Favero, J., Jordanova, A., De Jonghe, P. <strong>Mutations in SACS cause atypical and late-onset forms of ARSACS.</strong> Neurology 75: 1181-1188, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20876471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20876471</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181f4d86c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20876471">Baets et al. (2010)</a> stated that the SACS gene maps to chromosome 13q12.12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20876471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The mouse Sacs gene maps to chromosome 1, near D1Mit373 (<a href="#5" class="mim-tip-reference" title="Engert, J. C., Berube, P., Mercier, J., Dore, C., Lepage, P., Ge, B., Bouchard, J.-P., Mathieu, J., Melancon, S. B., Schalling, M., Lander, E. S., Morgan, K., Hudson, T. J., Richter, A. <strong>ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF.</strong> Nature Genet. 24: 120-125, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655055</a>] [<a href="https://doi.org/10.1038/72769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655055">Engert et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655055" 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="#9" class="mim-tip-reference" title="Parfitt, D. A., Michael, G. J., Vermeulen, E. G. M., Prodromou, N. V., Webb, T. R., Gallo, J.-M., Cheetham, M. E., Nicoll, W. S., Blatch, G. L., Chapple, J. P. <strong>The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1.</strong> Hum. Molec. Genet. 18: 1556-1565, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208651[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/10.1093/hmg/ddp067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208651">Parfitt et al. (2009)</a> determined that sacsin is most highly expressed in large neurons, including cerebellar Purkinje cells. Sacsin showed predominantly cytoplasmic localization with a mitochondrial component in neuroblastoma cells. The presence of both UBL and J-domains in sacsin suggested that it may integrate the ubiquitin-proteasome system and Hsp70 (HSPA1A; <a href="/entry/140550">140550</a>) function to a specific cellular role. Knockdown of SACS by siRNA did not affect viability of cells transfected with wildtype ataxin-1(30Q) (<a href="/entry/601556">601556</a>) but enhanced the toxicity of ataxin-1(82Q), suggesting that sacsin is protective against CAG-mutant ataxin-1. <a href="#9" class="mim-tip-reference" title="Parfitt, D. A., Michael, G. J., Vermeulen, E. G. M., Prodromou, N. V., Webb, T. R., Gallo, J.-M., Cheetham, M. E., Nicoll, W. S., Blatch, G. L., Chapple, J. P. <strong>The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1.</strong> Hum. Molec. Genet. 18: 1556-1565, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208651[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/10.1093/hmg/ddp067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208651">Parfitt et al. (2009)</a> concluded that sacsin is an ataxia protein and a regulator of the Hsp70 chaperone machinery that is implicated in the processing of other ataxia-linked proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19208651" 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>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS; <a href="/entry/270550">270550</a>) is an early-onset neurodegenerative disease with high prevalence (carrier frequency, 1 in 22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec, Canada. <a href="#5" class="mim-tip-reference" title="Engert, J. C., Berube, P., Mercier, J., Dore, C., Lepage, P., Ge, B., Bouchard, J.-P., Mathieu, J., Melancon, S. B., Schalling, M., Lander, E. S., Morgan, K., Hudson, T. J., Richter, A. <strong>ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF.</strong> Nature Genet. 24: 120-125, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655055</a>] [<a href="https://doi.org/10.1038/72769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655055">Engert et al. (2000)</a> identified 2 SACS mutations in ARSACS families that lead to protein truncation (<a href="#0001">604490.0001</a>-<a href="#0002">604490.0002</a>). The 2 different mutations corresponded to the 2 different haplotypes previously identified by <a href="#6" class="mim-tip-reference" title="Engert, J. C., Dore, C., Mercier, J., Ge, B., Betard, C., Rioux, J. D., Owen, C., Berube, P., Devon, K., Birren, B., Melancon, S. B., Morgan, K., Hudson, T. J., Richter, A. <strong>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): high-resolution physical and transcript map of the candidate region in chromosome region 13q11.</strong> Genomics 62: 156-164, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610707</a>] [<a href="https://doi.org/10.1006/geno.1999.6003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610707">Engert et al. (1999)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10655055+10610707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 Tunisian families with autosomal recessive ataxia phenotypically similar to ARSACS, 3 of which were consanguineous, <a href="#4" class="mim-tip-reference" title="El Euch-Fayache, G., Lalani, I., Amouri, R., Turki, I., Ouahchi, K., Hung, W.-Y., Belal, S., Siddique, T., Hentati, F. <strong>Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.</strong> Arch. Neurol. 60: 982-988, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12873855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12873855</a>] [<a href="https://doi.org/10.1001/archneur.60.7.982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12873855">El Euch-Fayache et al. (2003)</a> identified 4 mutations in the SACS gene (<a href="#0003">604490.0003</a>-<a href="#0006">604490.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12873855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Criscuolo, C., Banfi, S., Orio, M., Gasparini, P., Monticelli, A., Scarano, V., Santorelli, F. M., Perretti, A., Santoro, L., De Michele, G., Filla, A. <strong>A novel mutation in SACS gene in a family from southern Italy.</strong> Neurology 62: 100-102, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14718706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14718706</a>] [<a href="https://doi.org/10.1212/wnl.62.1.100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14718706">Criscuolo et al. (2004)</a> and <a href="#7" class="mim-tip-reference" title="Ogawa, T., Takiyama, Y., Sakoe, K., Mori, K., Namekawa, M., Shimazaki, H., Nakano, I., Nishizawa, M. <strong>Identification of a SACS gene missense mutation in ARSACS.</strong> Neurology 62: 107-109, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14718708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14718708</a>] [<a href="https://doi.org/10.1212/01.wnl.0000099371.14478.73" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14718708">Ogawa et al. (2004)</a> identified mutations in the SACS gene in ARSACS patients from southern Italy and Japan, respectively (see <a href="#0007">604490.0007</a> and <a href="#0008">604490.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14718708+14718706" 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="Richter, A. M., Ozgul, R. K., Poisson, V. C., Topaloglu, H. <strong>Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey.</strong> Neurogenetics 5: 165-170, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15156359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15156359</a>] [<a href="https://doi.org/10.1007/s10048-004-0179-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15156359">Richter et al. (2004)</a> identified 4 different homozygous mutations in the SACS gene in 4 Turkish families with ARSACS. A founder mutation was not identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15156359" 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 Japanese woman with ARSACS, <a href="#8" class="mim-tip-reference" title="Ouyang, Y., Takiyama, Y., Sakoe, K., Shimazaki, H., Ogawa, T., Nagano, S., Yamamoto, Y., Nakano, I. <strong>Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon.</strong> Neurology 66: 1103-1104, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606928</a>] [<a href="https://doi.org/10.1212/01.wnl.0000204300.94261.ea" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16606928">Ouyang et al. (2006)</a> identified compound heterozygosity for 2 mutations in exon 7 of the SACS gene (<a href="#0010">604490.0010</a>; <a href="#0011">604490.0011</a>). The patient had classic clinical features of early-onset spastic ataxia but no retinal hypermyelination. <a href="#8" class="mim-tip-reference" title="Ouyang, Y., Takiyama, Y., Sakoe, K., Shimazaki, H., Ogawa, T., Nagano, S., Yamamoto, Y., Nakano, I. <strong>Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon.</strong> Neurology 66: 1103-1104, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606928</a>] [<a href="https://doi.org/10.1212/01.wnl.0000204300.94261.ea" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16606928">Ouyang et al. (2006)</a> emphasized the need to examine all SACS exons, not only the gigantic exon 9, in patients with a clinical phenotype compatible with ARSACS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16606928" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Baets, J., Deconinck, T., Smets, K., Goossens, D., Van den Bergh, P., Dahan, K., Schmedding, E., Santens, P., Rasic, V. M., Van Damme, P., Robberecht, W., De Meirleir, L., Michielsens, B., Del-Favero, J., Jordanova, A., De Jonghe, P. <strong>Mutations in SACS cause atypical and late-onset forms of ARSACS.</strong> Neurology 75: 1181-1188, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20876471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20876471</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181f4d86c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20876471">Baets et al. (2010)</a> identified homozygous or compound heterozygous mutations in the SACS gene in 11 (12.9%) of 85 index patients with phenotypes suggestive of ARSACS. Eighteen different mutations were identified, including 11 missense, 5 frameshift, 1 nonsense, and 1 in-frame deletion. A founder allele was identified in 4 unrelated Belgian families. Five patients had onset after age 20 years, including 1 with onset at age 40. In addition, some patients presented with predominant features of peripheral neuropathy, although most eventually developed the classic signs of the disorder, namely cerebellar ataxia and pyramidal signs. Only 1 of 17 patients had mild mental retardation, and 2 had reduced IQ. There were no clear genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20876471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs281865117 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865117;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs281865117?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs281865117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs281865117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>Among patients with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>), 2 ancestral haplotypes had been identified (<a href="#6" class="mim-tip-reference" title="Engert, J. C., Dore, C., Mercier, J., Ge, B., Betard, C., Rioux, J. D., Owen, C., Berube, P., Devon, K., Birren, B., Melancon, S. B., Morgan, K., Hudson, T. J., Richter, A. <strong>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): high-resolution physical and transcript map of the candidate region in chromosome region 13q11.</strong> Genomics 62: 156-164, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610707</a>] [<a href="https://doi.org/10.1006/geno.1999.6003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610707">Engert et al., 1999</a>). <a href="#5" class="mim-tip-reference" title="Engert, J. C., Berube, P., Mercier, J., Dore, C., Lepage, P., Ge, B., Bouchard, J.-P., Mathieu, J., Melancon, S. B., Schalling, M., Lander, E. S., Morgan, K., Hudson, T. J., Richter, A. <strong>ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF.</strong> Nature Genet. 24: 120-125, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655055</a>] [<a href="https://doi.org/10.1038/72769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655055">Engert et al. (2000)</a> sequenced the DNA from ARSACS patients and controls and found a single-base deletion of a T at position 6594 on all copies of the major ancestral haplotype examined. This mutation resulted in a frameshift and introduction of a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10655055+10610707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Criscuolo, C., Banfi, S., Orio, M., Gasparini, P., Monticelli, A., Scarano, V., Santorelli, F. M., Perretti, A., Santoro, L., De Michele, G., Filla, A. <strong>A novel mutation in SACS gene in a family from southern Italy.</strong> Neurology 62: 100-102, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14718706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14718706</a>] [<a href="https://doi.org/10.1212/wnl.62.1.100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14718706">Criscuolo et al. (2004)</a> stated that the 6594delT mutation accounts for approximately 94% of the disease alleles among individuals in the French Canadian population with ARSACS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14718706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs281865118 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865118;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs281865118?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs281865118" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs281865118" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005848 OR RCV000984887 OR RCV001268308 OR RCV001847584 OR RCV001851681" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005848, RCV000984887, RCV001268308, RCV001847584, RCV001851681" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005848...</a>
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<p><a href="#5" class="mim-tip-reference" title="Engert, J. C., Berube, P., Mercier, J., Dore, C., Lepage, P., Ge, B., Bouchard, J.-P., Mathieu, J., Melancon, S. B., Schalling, M., Lander, E. S., Morgan, K., Hudson, T. J., Richter, A. <strong>ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF.</strong> Nature Genet. 24: 120-125, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655055</a>] [<a href="https://doi.org/10.1038/72769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10655055">Engert et al. (2000)</a> found a C-to-T transition at nucleotide 5254 of the SACS gene in 6 patients with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>) who carried the minor haplotype. The 5254C-T mutation, which predicts the substitution of a stop codon for arginine, was found in compound heterozygous state with the 6594delT mutation (<a href="#0001">604490.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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SACS, ALA3324PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853016 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853016;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005849" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005849" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005849</a>
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<p>In a Tunisian family with autosomal recessive ataxia similar to spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>), <a href="#4" class="mim-tip-reference" title="El Euch-Fayache, G., Lalani, I., Amouri, R., Turki, I., Ouahchi, K., Hung, W.-Y., Belal, S., Siddique, T., Hentati, F. <strong>Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.</strong> Arch. Neurol. 60: 982-988, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12873855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12873855</a>] [<a href="https://doi.org/10.1001/archneur.60.7.982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12873855">El Euch-Fayache et al. (2003)</a> identified a 10046G-C transversion in the SACS gene, resulting in an ala3324-to-pro (A3324P) substitution. The mutation was not identified in 100 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12873855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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SACS, 1-BP DEL, 1411T
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2137634136 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2137634136;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2137634136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2137634136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005850" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005850" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005850</a>
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<p>In a Tunisian family with autosomal recessive ataxia similar to spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>), <a href="#4" class="mim-tip-reference" title="El Euch-Fayache, G., Lalani, I., Amouri, R., Turki, I., Ouahchi, K., Hung, W.-Y., Belal, S., Siddique, T., Hentati, F. <strong>Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.</strong> Arch. Neurol. 60: 982-988, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12873855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12873855</a>] [<a href="https://doi.org/10.1001/archneur.60.7.982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12873855">El Euch-Fayache et al. (2003)</a> identified a 1-bp deletion (1411delT) in the SACS gene, resulting in a premature stop codon and a truncated peptide of 456 amino acids. The mutation was not identified in 100 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12873855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<strong>.0005 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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SACS, 1-BP INS, 1155A
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs770866403 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs770866403;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs770866403?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs770866403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs770866403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000169583 OR RCV001850406" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000169583, RCV001850406" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000169583...</a>
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<p>In a Tunisian family with autosomal recessive ataxia similar to spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>), <a href="#4" class="mim-tip-reference" title="El Euch-Fayache, G., Lalani, I., Amouri, R., Turki, I., Ouahchi, K., Hung, W.-Y., Belal, S., Siddique, T., Hentati, F. <strong>Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.</strong> Arch. Neurol. 60: 982-988, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12873855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12873855</a>] [<a href="https://doi.org/10.1001/archneur.60.7.982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12873855">El Euch-Fayache et al. (2003)</a> identified a 1-bp insertion (1155insA) in the SACS gene, producing a truncated peptide of 360 amino acids. The mutation was not identified in 100 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12873855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<strong>.0006 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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SACS, TRP1196ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853017 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853017;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853017" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853017" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005852 OR RCV001851682 OR RCV003415662" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005852, RCV001851682, RCV003415662" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005852...</a>
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<p>In a Tunisian family with autosomal recessive ataxia similar to spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>), <a href="#4" class="mim-tip-reference" title="El Euch-Fayache, G., Lalani, I., Amouri, R., Turki, I., Ouahchi, K., Hung, W.-Y., Belal, S., Siddique, T., Hentati, F. <strong>Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.</strong> Arch. Neurol. 60: 982-988, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12873855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12873855</a>] [<a href="https://doi.org/10.1001/archneur.60.7.982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12873855">El Euch-Fayache et al. (2003)</a> identified a 3662T-C transition in the SACS gene, resulting in a trp1196-to-arg (W1196R) substitution. The mutation was not identified in 100 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12873855" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0007 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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SACS, 1-BP INS, 1859C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs606231163 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs606231163;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs606231163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs606231163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005853" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005853" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005853</a>
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<span class="mim-text-font">
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<p>In 2 sisters with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>), born of consanguineous parents in southern Italy, <a href="#2" class="mim-tip-reference" title="Criscuolo, C., Banfi, S., Orio, M., Gasparini, P., Monticelli, A., Scarano, V., Santorelli, F. M., Perretti, A., Santoro, L., De Michele, G., Filla, A. <strong>A novel mutation in SACS gene in a family from southern Italy.</strong> Neurology 62: 100-102, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14718706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14718706</a>] [<a href="https://doi.org/10.1212/wnl.62.1.100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14718706">Criscuolo et al. (2004)</a> identified homozygosity for a 1-bp insertion, 1859insC, in the SACS gene, resulting in a frameshift and a premature stop codon at position 599. The resulting protein lacked 3,230 amino acids. Both sisters showed a clinical phenotype similar to other reported patients with ARSACS; one of the sisters also had mental retardation and hypoacusis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14718706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853018 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853018;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137853018?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005854" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005854" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005854</a>
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<p>In a Japanese sister and brother with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>), <a href="#7" class="mim-tip-reference" title="Ogawa, T., Takiyama, Y., Sakoe, K., Mori, K., Namekawa, M., Shimazaki, H., Nakano, I., Nishizawa, M. <strong>Identification of a SACS gene missense mutation in ARSACS.</strong> Neurology 62: 107-109, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14718708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14718708</a>] [<a href="https://doi.org/10.1212/01.wnl.0000099371.14478.73" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14718708">Ogawa et al. (2004)</a> identified a homozygous 7492T-C transition in the SACS gene, resulting in a trp2498-to-arg (W2498R) substitution in a conserved residue. The mutation was not found in 200 Japanese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14718708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853019 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853019;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005855" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005855" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005855</a>
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<p>In 2 Japanese brothers, born of consanguineous parents, with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>), <a href="#12" class="mim-tip-reference" title="Shimazaki, H., Takiyama, Y., Sakoe, K., Ando, Y., Nakano, I. <strong>A phenotype without spasticity in sacsin-related ataxia.</strong> Neurology 64: 2129-2131, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15985586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15985586</a>] [<a href="https://doi.org/10.1212/01.WNL.0000166031.91514.B3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15985586">Shimazaki et al. (2005)</a> identified a homozygous 987T-C transition in the SACS gene, resulting in a phe304-to-ser (F304S) substitution. Each parent was heterozygous for the mutation, which was not identified in 208 control chromosomes. The phenotype was unique in that neither patient had spasticity or hyperreflexia, although both had extensor plantar responses, indicating pyramidal tract dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15985586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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SACS, 10-BP DEL, NT32627
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2137724246 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2137724246;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2137724246" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2137724246" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005856" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005856" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005856</a>
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<p>In a Japanese woman with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>), <a href="#8" class="mim-tip-reference" title="Ouyang, Y., Takiyama, Y., Sakoe, K., Shimazaki, H., Ogawa, T., Nagano, S., Yamamoto, Y., Nakano, I. <strong>Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon.</strong> Neurology 66: 1103-1104, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606928</a>] [<a href="https://doi.org/10.1212/01.wnl.0000204300.94261.ea" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16606928">Ouyang et al. (2006)</a> identified compound heterozygosity for 2 mutations in exon 7 of the SACS gene: a 10-bp deletion (32627delACACTGTTAC) and a 1-bp deletion (31760delT; <a href="#0011">604490.0011</a>). Both mutations were predicted to result in premature termination of the protein; each unaffected parent was heterozygous for 1 of the mutations. The patient had classic clinical features of early-onset spastic ataxia but no retinal hypermyelination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16606928" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2137716138 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2137716138;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2137716138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2137716138" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005857" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005857" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005857</a>
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<p>For discussion of the 1-bp deletion in the SACS gene (31760delT) that was found in compound heterozygous state in a patient with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; <a href="/entry/270550">270550</a>) by <a href="#8" class="mim-tip-reference" title="Ouyang, Y., Takiyama, Y., Sakoe, K., Shimazaki, H., Ogawa, T., Nagano, S., Yamamoto, Y., Nakano, I. <strong>Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon.</strong> Neurology 66: 1103-1104, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606928</a>] [<a href="https://doi.org/10.1212/01.wnl.0000204300.94261.ea" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16606928">Ouyang et al. (2006)</a>, see <a href="#0010">604490.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16606928" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Baets, J., Deconinck, T., Smets, K., Goossens, D., Van den Bergh, P., Dahan, K., Schmedding, E., Santens, P., Rasic, V. M., Van Damme, P., Robberecht, W., De Meirleir, L., Michielsens, B., Del-Favero, J., Jordanova, A., De Jonghe, P.
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<strong>Mutations in SACS cause atypical and late-onset forms of ARSACS.</strong>
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Neurology 75: 1181-1188, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20876471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20876471</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20876471" 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.0b013e3181f4d86c" target="_blank">Full Text</a>]
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Criscuolo, C., Banfi, S., Orio, M., Gasparini, P., Monticelli, A., Scarano, V., Santorelli, F. M., Perretti, A., Santoro, L., De Michele, G., Filla, A.
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<strong>A novel mutation in SACS gene in a family from southern Italy.</strong>
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Neurology 62: 100-102, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14718706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14718706</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14718706" 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.62.1.100" target="_blank">Full Text</a>]
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Dickie, M. M.
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<strong>Tumbler, tb.</strong>
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Mouse News Lett. 32: 45 only, 1965.
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<div class="">
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<p class="mim-text-font">
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El Euch-Fayache, G., Lalani, I., Amouri, R., Turki, I., Ouahchi, K., Hung, W.-Y., Belal, S., Siddique, T., Hentati, F.
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<strong>Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.</strong>
|
|
Arch. Neurol. 60: 982-988, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12873855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12873855</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12873855" 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.60.7.982" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Engert2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Engert, J. C., Berube, P., Mercier, J., Dore, C., Lepage, P., Ge, B., Bouchard, J.-P., Mathieu, J., Melancon, S. B., Schalling, M., Lander, E. S., Morgan, K., Hudson, T. J., Richter, A.
|
|
<strong>ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF.</strong>
|
|
Nature Genet. 24: 120-125, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10655055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10655055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10655055" 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/10.1038/72769" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Engert1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Engert, J. C., Dore, C., Mercier, J., Ge, B., Betard, C., Rioux, J. D., Owen, C., Berube, P., Devon, K., Birren, B., Melancon, S. B., Morgan, K., Hudson, T. J., Richter, A.
|
|
<strong>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): high-resolution physical and transcript map of the candidate region in chromosome region 13q11.</strong>
|
|
Genomics 62: 156-164, 1999.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10610707" 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/10.1006/geno.1999.6003" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Ogawa2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ogawa, T., Takiyama, Y., Sakoe, K., Mori, K., Namekawa, M., Shimazaki, H., Nakano, I., Nishizawa, M.
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|
<strong>Identification of a SACS gene missense mutation in ARSACS.</strong>
|
|
Neurology 62: 107-109, 2004.
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14718708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14718708</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14718708" 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/10.1212/01.wnl.0000099371.14478.73" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Ouyang2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ouyang, Y., Takiyama, Y., Sakoe, K., Shimazaki, H., Ogawa, T., Nagano, S., Yamamoto, Y., Nakano, I.
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<strong>Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon.</strong>
|
|
Neurology 66: 1103-1104, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606928</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16606928" 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/10.1212/01.wnl.0000204300.94261.ea" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Parfitt2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Parfitt, D. A., Michael, G. J., Vermeulen, E. G. M., Prodromou, N. V., Webb, T. R., Gallo, J.-M., Cheetham, M. E., Nicoll, W. S., Blatch, G. L., Chapple, J. P.
|
|
<strong>The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1.</strong>
|
|
Hum. Molec. Genet. 18: 1556-1565, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208651</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208651[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19208651" 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/hmg/ddp067" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Richter2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Richter, A. M., Ozgul, R. K., Poisson, V. C., Topaloglu, H.
|
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<strong>Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey.</strong>
|
|
Neurogenetics 5: 165-170, 2004.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15156359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15156359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15156359" 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/s10048-004-0179-y" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Romano2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Romano, A., Tessa, A., Barca, A., Fattori, F., de Leva, M. F., Terracciano, A., Storelli, C., Santorelli, F. M., Verri, T.
|
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<strong>Comparative analysis and functional mapping of SACS mutations reveal novel insights into sacsin repeated architecture.</strong>
|
|
Hum. Mutat. 34: 525-537, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23280630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23280630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23280630[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23280630" 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/humu.22269" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Shimazaki2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shimazaki, H., Takiyama, Y., Sakoe, K., Ando, Y., Nakano, I.
|
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<strong>A phenotype without spasticity in sacsin-related ataxia.</strong>
|
|
Neurology 64: 2129-2131, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15985586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15985586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15985586" 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/10.1212/01.WNL.0000166031.91514.B3" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 4/4/2013
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 7/21/2011<br>George E. Tiller - updated : 10/15/2009<br>Cassandra L. Kniffin - updated : 7/30/2007<br>Cassandra L. Kniffin - updated : 10/31/2005<br>Cassandra L. Kniffin - updated : 10/22/2004<br>Cassandra L. Kniffin - updated : 8/26/2004<br>Cassandra L. Kniffin - updated : 8/7/2003
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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>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 2/1/2000
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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>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/18/2015
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mcolton : 8/12/2015<br>carol : 11/19/2014<br>carol : 2/21/2014<br>carol : 9/27/2013<br>alopez : 4/8/2013<br>ckniffin : 4/4/2013<br>terry : 10/26/2011<br>alopez : 10/4/2011<br>wwang : 8/12/2011<br>ckniffin : 7/21/2011<br>wwang : 10/20/2009<br>terry : 10/15/2009<br>wwang : 8/22/2007<br>ckniffin : 7/30/2007<br>wwang : 11/3/2005<br>ckniffin : 10/31/2005<br>ckniffin : 10/22/2004<br>tkritzer : 9/8/2004<br>ckniffin : 8/26/2004<br>tkritzer : 8/14/2003<br>ckniffin : 8/7/2003<br>terry : 10/6/2000<br>alopez : 2/2/2000<br>alopez : 2/1/2000
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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>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 604490
|
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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SACSIN; SACS
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</span>
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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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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SACS</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 702445005;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
|
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<em>
|
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Cytogenetic location: 13q12.12
|
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Genomic coordinates <span class="small">(GRCh38)</span> : 13:23,328,830-23,433,702 </span>
|
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</em>
|
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</strong>
|
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<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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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>Gene-Phenotype 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 small mim-table-padding">
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<thead>
|
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<tr class="active">
|
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<th>
|
|
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>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
|
13q12.12
|
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</span>
|
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</td>
|
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|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Spastic ataxia, Charlevoix-Saguenay type
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
270550
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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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>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The SACS gene encodes sacsin, a protein believed to integrate the ubiquitin-proteasome system and Hsp70 chaperone machinery and implicated in the processing of ataxin-1 (ATXN1; 601556) (Parfitt et al., 2009). </p>
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</span>
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<div>
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<br />
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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>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Engert et al. (2000) reported the cloning of the SACS gene, which encodes the protein sacsin. The open reading frame is conserved in human and mouse. Sequence analysis of the 3,829-amino acid SACS protein predicted 2 leucine zippers, 3 coiled-coils, and 7 nuclear localization signals. The C-terminal portion of the protein contains a hydrophilic domain and a DnaJ motif (see 604189). The putative protein contains 3 large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana open reading frame. The presence of heat-shock domains suggested a function for sacsin in chaperone-mediated protein folding. Northern blot analysis detected SACS expression as a 12.8-kb transcript in fibroblasts, brain, skeletal muscle, and at low levels in pancreas. In situ hybridization to human, monkey, and rat brain tissue showed intense labeling in all areas of the central nervous system. </p><p>With the finding of 8 additional exons, the SACS gene is predicted to encode a 4,579-amino acid protein (Ouyang et al., 2006). Parfitt et al. (2009) identified an ubiquitin-like (UBL) domain in the N terminus of sacsin that interacted with the proteasome. </p><p>Romano et al. (2013) characterized the 3 sacsin repeating region (SRR) supradomains and determined that they are much larger (1,100 residues or more) than previously reported. These regions are organized into discrete subrepeats. The large repeated regions were termed 'Sacsin Internal RePeaTs' (SIRPT1, SIRPT2, and SIRPT3), and the subrepeats sr1, sr2, sr3, and srX. Comparative analysis of vertebrate sacsins showed that these regions are highly conserved among vertebrates. Fine positional mapping of a set of human SACS mutations revealed that sr1, sr2, sr3, and srX are functional. In addition, the position of the pathogenic mutations in sr1, sr2, sr3, and srX appeared to be related to the severity of the clinical phenotype, as assessed by defining a severity scoring system. These results suggested that the relative position of mutations in subrepeats will variably influence sacsin dysfunction. </p>
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</span>
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<div>
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<br />
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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>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Engert et al. (2000) found that the 11,487-bp open reading frame of SACS is encoded by a single gigantic exon spanning 12,794 bp. This exon was the largest to be identified in any vertebrate organism. The largest exons previously reported were those of the X inactivation-specific transcript (XIST; 314670), which does not encode a protein, 11,363 bp; and an exon of the mucin gene (MUC5B; 600770), measuring 10,713 bp. </p><p>Eight novel exons located upstream of the gigantic exon have been identified, bringing the total number of exons in the SACS gene to 9. The gigantic exon is referred to as exon 9 (Ouyang et al., 2006). </p>
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</span>
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<div>
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<br />
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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>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Baets et al. (2010) stated that the SACS gene maps to chromosome 13q12.12. </p><p>The mouse Sacs gene maps to chromosome 1, near D1Mit373 (Engert et al., 2000). </p>
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</span>
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<div>
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<br />
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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>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Parfitt et al. (2009) determined that sacsin is most highly expressed in large neurons, including cerebellar Purkinje cells. Sacsin showed predominantly cytoplasmic localization with a mitochondrial component in neuroblastoma cells. The presence of both UBL and J-domains in sacsin suggested that it may integrate the ubiquitin-proteasome system and Hsp70 (HSPA1A; 140550) function to a specific cellular role. Knockdown of SACS by siRNA did not affect viability of cells transfected with wildtype ataxin-1(30Q) (601556) but enhanced the toxicity of ataxin-1(82Q), suggesting that sacsin is protective against CAG-mutant ataxin-1. Parfitt et al. (2009) concluded that sacsin is an ataxia protein and a regulator of the Hsp70 chaperone machinery that is implicated in the processing of other ataxia-linked proteins. </p>
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</span>
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<div>
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<br />
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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>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS; 270550) is an early-onset neurodegenerative disease with high prevalence (carrier frequency, 1 in 22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec, Canada. Engert et al. (2000) identified 2 SACS mutations in ARSACS families that lead to protein truncation (604490.0001-604490.0002). The 2 different mutations corresponded to the 2 different haplotypes previously identified by Engert et al. (1999). </p><p>In 4 Tunisian families with autosomal recessive ataxia phenotypically similar to ARSACS, 3 of which were consanguineous, El Euch-Fayache et al. (2003) identified 4 mutations in the SACS gene (604490.0003-604490.0006). </p><p>Criscuolo et al. (2004) and Ogawa et al. (2004) identified mutations in the SACS gene in ARSACS patients from southern Italy and Japan, respectively (see 604490.0007 and 604490.0008). </p><p>Richter et al. (2004) identified 4 different homozygous mutations in the SACS gene in 4 Turkish families with ARSACS. A founder mutation was not identified. </p><p>In a Japanese woman with ARSACS, Ouyang et al. (2006) identified compound heterozygosity for 2 mutations in exon 7 of the SACS gene (604490.0010; 604490.0011). The patient had classic clinical features of early-onset spastic ataxia but no retinal hypermyelination. Ouyang et al. (2006) emphasized the need to examine all SACS exons, not only the gigantic exon 9, in patients with a clinical phenotype compatible with ARSACS. </p><p>Baets et al. (2010) identified homozygous or compound heterozygous mutations in the SACS gene in 11 (12.9%) of 85 index patients with phenotypes suggestive of ARSACS. Eighteen different mutations were identified, including 11 missense, 5 frameshift, 1 nonsense, and 1 in-frame deletion. A founder allele was identified in 4 unrelated Belgian families. Five patients had onset after age 20 years, including 1 with onset at age 40. In addition, some patients presented with predominant features of peripheral neuropathy, although most eventually developed the classic signs of the disorder, namely cerebellar ataxia and pyramidal signs. Only 1 of 17 patients had mild mental retardation, and 2 had reduced IQ. There were no clear genotype/phenotype correlations. </p>
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</span>
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<div>
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<br />
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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>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>A recessive mouse mutation, 'tumbler' (tb), was previously mapped to chromosome 1 by linkage (Dickie, 1965). Tumbler mice had ataxia, causing them to walk in a crab-like fashion and fall over when trying to move forward. The tb mouse line had died out, but Engert et al. (2000) speculated that it harbored a mutation in Sacs. </p>
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</span>
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<div>
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<br />
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</div>
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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>ALLELIC VARIANTS</strong>
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</span>
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<strong>11 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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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>.0001 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SACS, 1-BP DEL, 6594T
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<br />
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SNP: rs281865117,
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gnomAD: rs281865117,
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ClinVar: RCV000005847, RCV000338359, RCV000460039, RCV001847583, RCV004748502
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Among patients with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550), 2 ancestral haplotypes had been identified (Engert et al., 1999). Engert et al. (2000) sequenced the DNA from ARSACS patients and controls and found a single-base deletion of a T at position 6594 on all copies of the major ancestral haplotype examined. This mutation resulted in a frameshift and introduction of a stop codon. </p><p>Criscuolo et al. (2004) stated that the 6594delT mutation accounts for approximately 94% of the disease alleles among individuals in the French Canadian population with ARSACS. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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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>.0002 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SACS, 5254C-T
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<br />
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SNP: rs281865118,
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gnomAD: rs281865118,
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ClinVar: RCV000005848, RCV000984887, RCV001268308, RCV001847584, RCV001851681
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Engert et al. (2000) found a C-to-T transition at nucleotide 5254 of the SACS gene in 6 patients with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550) who carried the minor haplotype. The 5254C-T mutation, which predicts the substitution of a stop codon for arginine, was found in compound heterozygous state with the 6594delT mutation (604490.0001). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0003 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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|
SACS, ALA3324PRO
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<br />
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SNP: rs137853016,
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ClinVar: RCV000005849
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Tunisian family with autosomal recessive ataxia similar to spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550), El Euch-Fayache et al. (2003) identified a 10046G-C transversion in the SACS gene, resulting in an ala3324-to-pro (A3324P) substitution. The mutation was not identified in 100 control chromosomes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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|
<span class="mim-font">
|
|
<strong>.0004 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SACS, 1-BP DEL, 1411T
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<br />
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SNP: rs2137634136,
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ClinVar: RCV000005850
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Tunisian family with autosomal recessive ataxia similar to spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550), El Euch-Fayache et al. (2003) identified a 1-bp deletion (1411delT) in the SACS gene, resulting in a premature stop codon and a truncated peptide of 456 amino acids. The mutation was not identified in 100 control chromosomes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0005 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SACS, 1-BP INS, 1155A
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<br />
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SNP: rs770866403,
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gnomAD: rs770866403,
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ClinVar: RCV000169583, RCV001850406
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Tunisian family with autosomal recessive ataxia similar to spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550), El Euch-Fayache et al. (2003) identified a 1-bp insertion (1155insA) in the SACS gene, producing a truncated peptide of 360 amino acids. The mutation was not identified in 100 control chromosomes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0006 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SACS, TRP1196ARG
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<br />
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SNP: rs137853017,
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ClinVar: RCV000005852, RCV001851682, RCV003415662
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Tunisian family with autosomal recessive ataxia similar to spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550), El Euch-Fayache et al. (2003) identified a 3662T-C transition in the SACS gene, resulting in a trp1196-to-arg (W1196R) substitution. The mutation was not identified in 100 control chromosomes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0007 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SACS, 1-BP INS, 1859C
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<br />
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SNP: rs606231163,
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ClinVar: RCV000005853
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 2 sisters with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550), born of consanguineous parents in southern Italy, Criscuolo et al. (2004) identified homozygosity for a 1-bp insertion, 1859insC, in the SACS gene, resulting in a frameshift and a premature stop codon at position 599. The resulting protein lacked 3,230 amino acids. Both sisters showed a clinical phenotype similar to other reported patients with ARSACS; one of the sisters also had mental retardation and hypoacusis. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0008 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
|
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</span>
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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SACS, TRP2498ARG
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<br />
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SNP: rs137853018,
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gnomAD: rs137853018,
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ClinVar: RCV000005854
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a Japanese sister and brother with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550), Ogawa et al. (2004) identified a homozygous 7492T-C transition in the SACS gene, resulting in a trp2498-to-arg (W2498R) substitution in a conserved residue. The mutation was not found in 200 Japanese controls. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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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>.0009 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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SACS, PHE304SER
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<br />
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SNP: rs137853019,
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ClinVar: RCV000005855
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<p>In 2 Japanese brothers, born of consanguineous parents, with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550), Shimazaki et al. (2005) identified a homozygous 987T-C transition in the SACS gene, resulting in a phe304-to-ser (F304S) substitution. Each parent was heterozygous for the mutation, which was not identified in 208 control chromosomes. The phenotype was unique in that neither patient had spasticity or hyperreflexia, although both had extensor plantar responses, indicating pyramidal tract dysfunction. </p>
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<span class="mim-font">
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<strong>.0010 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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SACS, 10-BP DEL, NT32627
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<br />
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SNP: rs2137724246,
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ClinVar: RCV000005856
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<p>In a Japanese woman with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550), Ouyang et al. (2006) identified compound heterozygosity for 2 mutations in exon 7 of the SACS gene: a 10-bp deletion (32627delACACTGTTAC) and a 1-bp deletion (31760delT; 604490.0011). Both mutations were predicted to result in premature termination of the protein; each unaffected parent was heterozygous for 1 of the mutations. The patient had classic clinical features of early-onset spastic ataxia but no retinal hypermyelination. </p>
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<h4>
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<span class="mim-font">
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<strong>.0011 SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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SACS, 1-BP DEL, 31760T
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<br />
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SNP: rs2137716138,
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ClinVar: RCV000005857
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</span>
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<span class="mim-text-font">
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<p>For discussion of the 1-bp deletion in the SACS gene (31760delT) that was found in compound heterozygous state in a patient with spastic ataxia of the Charlevoix-Saguenay type (ARSACS; 270550) by Ouyang et al. (2006), see 604490.0010. </p>
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</span>
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</div>
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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>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Baets, J., Deconinck, T., Smets, K., Goossens, D., Van den Bergh, P., Dahan, K., Schmedding, E., Santens, P., Rasic, V. M., Van Damme, P., Robberecht, W., De Meirleir, L., Michielsens, B., Del-Favero, J., Jordanova, A., De Jonghe, P.
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<strong>Mutations in SACS cause atypical and late-onset forms of ARSACS.</strong>
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Neurology 75: 1181-1188, 2010.
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[PubMed: 20876471]
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[Full Text: https://doi.org/10.1212/WNL.0b013e3181f4d86c]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Criscuolo, C., Banfi, S., Orio, M., Gasparini, P., Monticelli, A., Scarano, V., Santorelli, F. M., Perretti, A., Santoro, L., De Michele, G., Filla, A.
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<strong>A novel mutation in SACS gene in a family from southern Italy.</strong>
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Neurology 62: 100-102, 2004.
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[PubMed: 14718706]
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[Full Text: https://doi.org/10.1212/wnl.62.1.100]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dickie, M. M.
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<strong>Tumbler, tb.</strong>
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Mouse News Lett. 32: 45 only, 1965.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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El Euch-Fayache, G., Lalani, I., Amouri, R., Turki, I., Ouahchi, K., Hung, W.-Y., Belal, S., Siddique, T., Hentati, F.
|
|
<strong>Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.</strong>
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Arch. Neurol. 60: 982-988, 2003.
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[PubMed: 12873855]
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[Full Text: https://doi.org/10.1001/archneur.60.7.982]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Engert, J. C., Berube, P., Mercier, J., Dore, C., Lepage, P., Ge, B., Bouchard, J.-P., Mathieu, J., Melancon, S. B., Schalling, M., Lander, E. S., Morgan, K., Hudson, T. J., Richter, A.
|
|
<strong>ARSACS, a spastic ataxia common in northeastern Quebec, is caused by mutations in a new gene encoding an 11.5-kb ORF.</strong>
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Nature Genet. 24: 120-125, 2000.
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[PubMed: 10655055]
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[Full Text: https://doi.org/10.1038/72769]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Engert, J. C., Dore, C., Mercier, J., Ge, B., Betard, C., Rioux, J. D., Owen, C., Berube, P., Devon, K., Birren, B., Melancon, S. B., Morgan, K., Hudson, T. J., Richter, A.
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|
<strong>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): high-resolution physical and transcript map of the candidate region in chromosome region 13q11.</strong>
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Genomics 62: 156-164, 1999.
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[PubMed: 10610707]
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[Full Text: https://doi.org/10.1006/geno.1999.6003]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ogawa, T., Takiyama, Y., Sakoe, K., Mori, K., Namekawa, M., Shimazaki, H., Nakano, I., Nishizawa, M.
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<strong>Identification of a SACS gene missense mutation in ARSACS.</strong>
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Neurology 62: 107-109, 2004.
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[PubMed: 14718708]
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[Full Text: https://doi.org/10.1212/01.wnl.0000099371.14478.73]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ouyang, Y., Takiyama, Y., Sakoe, K., Shimazaki, H., Ogawa, T., Nagano, S., Yamamoto, Y., Nakano, I.
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<strong>Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon.</strong>
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Neurology 66: 1103-1104, 2006.
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[PubMed: 16606928]
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[Full Text: https://doi.org/10.1212/01.wnl.0000204300.94261.ea]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Parfitt, D. A., Michael, G. J., Vermeulen, E. G. M., Prodromou, N. V., Webb, T. R., Gallo, J.-M., Cheetham, M. E., Nicoll, W. S., Blatch, G. L., Chapple, J. P.
|
|
<strong>The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1.</strong>
|
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Hum. Molec. Genet. 18: 1556-1565, 2009.
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[PubMed: 19208651]
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[Full Text: https://doi.org/10.1093/hmg/ddp067]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Richter, A. M., Ozgul, R. K., Poisson, V. C., Topaloglu, H.
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<strong>Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey.</strong>
|
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Neurogenetics 5: 165-170, 2004.
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[PubMed: 15156359]
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[Full Text: https://doi.org/10.1007/s10048-004-0179-y]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Romano, A., Tessa, A., Barca, A., Fattori, F., de Leva, M. F., Terracciano, A., Storelli, C., Santorelli, F. M., Verri, T.
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<strong>Comparative analysis and functional mapping of SACS mutations reveal novel insights into sacsin repeated architecture.</strong>
|
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Hum. Mutat. 34: 525-537, 2013.
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[PubMed: 23280630]
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[Full Text: https://doi.org/10.1002/humu.22269]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Shimazaki, H., Takiyama, Y., Sakoe, K., Ando, Y., Nakano, I.
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<strong>A phenotype without spasticity in sacsin-related ataxia.</strong>
|
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Neurology 64: 2129-2131, 2005.
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[PubMed: 15985586]
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[Full Text: https://doi.org/10.1212/01.WNL.0000166031.91514.B3]
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Cassandra L. Kniffin - updated : 4/4/2013<br>Cassandra L. Kniffin - updated : 7/21/2011<br>George E. Tiller - updated : 10/15/2009<br>Cassandra L. Kniffin - updated : 7/30/2007<br>Cassandra L. Kniffin - updated : 10/31/2005<br>Cassandra L. Kniffin - updated : 10/22/2004<br>Cassandra L. Kniffin - updated : 8/26/2004<br>Cassandra L. Kniffin - updated : 8/7/2003
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