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Entry
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- *606725 - CLN6 TRANSMEMBRANE ER PROTEIN; CLN6
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- OMIM
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</form>
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<div class="row">
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<p />
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</div>
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*606725</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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</li>
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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>
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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>
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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>
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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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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606725">Table View</a>
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</li>
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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>
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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=ENSG00000128973;t=ENST00000249806" 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=54982" 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=606725" 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=ENSG00000128973;t=ENST00000249806" 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_001411068,NM_017882" 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_017882" 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=606725" 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=05991&isoform_id=05991_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/CLN6" 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/7020752,8923532,14042394,14790000,15341893,22760400,32129457,48146605,119598217,119598218,119598219,119598220,119598221,119598222,158255786,194375510,194375584,957951224,957951228,957951231,957951234,2288045687" 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/Q9NWW5" 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=54982" 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=ENSG00000128973;t=ENST00000249806" 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=CLN6" 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=CLN6" 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+54982" 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/CLN6" 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:54982" 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/54982" 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=chr15&hgg_gene=ENST00000249806.11&hgg_start=68206992&hgg_end=68257211&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">
|
|
<span class="panel-title">
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<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</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/genes/HGNC:2077" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/cln6" 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=606725[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=606725[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/CLN6/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/ENSG00000128973" 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=CLN6" 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=CLN6" 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=CLN6" 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.ucl.ac.uk/ncl/" 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=CLN6&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/PA26604" 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:2077" 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:2159324" 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/CLN6#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:2159324" 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/54982/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/OMIA001443/" 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=54982" 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-041010-57" 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">
|
|
<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">
|
|
<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=CLN6&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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</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>
|
|
606725
|
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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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CLN6 TRANSMEMBRANE ER PROTEIN; CLN6
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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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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CLN6 GENE
|
|
</span>
|
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</h4>
|
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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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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CLN6" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CLN6</a></em></strong>
|
|
</span>
|
|
</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/15/326?start=-3&limit=10&highlight=326">15q23</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:68206992-68257211&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'})">15:68,206,992-68,257,211</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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|
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</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=601780,204300" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
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<tbody>
|
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<tr>
|
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<td rowspan="2">
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<p>By positional cloning in the candidate region for variant late infantile neuronal ceroid lipofuscinosis (vLINCL, CLN6A; <a href="/entry/601780">601780</a>) on chromosome 15q21-q23, <a href="#8" class="mim-tip-reference" title="Gao, H., Boustany, R.-M. N., Espinola, J. A., Cotman, S. L., Srinidhi, L., Antonellis, K. A., Gillis, T., Qin, X., Liu, S., Donahue, L. R., Bronson, R. T., Faust, J. R., Stout, D., Haines, J. L., Lerner, T. J., MacDonald, M. E. <strong>Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.</strong> Am. J. Hum. Genet. 70: 324-335, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11791207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11791207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11791207[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/10.1086/338190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11791207">Gao et al. (2002)</a> identified the CLN6 (FLJ0561) gene. CLN6 encodes a deduced 311-amino acid protein with 7 predicted transmembrane domains and a predicted molecular mass of 36 kD. Northern blot analysis detected expression of a major 2.4-kb CLN6 mRNA in adult and embryonic brain and in peripheral tissues of mouse and human. The protein is conserved across vertebrates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11791207" 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="#8" class="mim-tip-reference" title="Gao, H., Boustany, R.-M. N., Espinola, J. A., Cotman, S. L., Srinidhi, L., Antonellis, K. A., Gillis, T., Qin, X., Liu, S., Donahue, L. R., Bronson, R. T., Faust, J. R., Stout, D., Haines, J. L., Lerner, T. J., MacDonald, M. E. <strong>Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.</strong> Am. J. Hum. Genet. 70: 324-335, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11791207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11791207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11791207[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/10.1086/338190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11791207">Gao et al. (2002)</a> determined that the CLN6 gene contains 7 exons that span approximately 23 kb of genomic DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11791207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By sequence analysis, <a href="#8" class="mim-tip-reference" title="Gao, H., Boustany, R.-M. N., Espinola, J. A., Cotman, S. L., Srinidhi, L., Antonellis, K. A., Gillis, T., Qin, X., Liu, S., Donahue, L. R., Bronson, R. T., Faust, J. R., Stout, D., Haines, J. L., Lerner, T. J., MacDonald, M. E. <strong>Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.</strong> Am. J. Hum. Genet. 70: 324-335, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11791207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11791207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11791207[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/10.1086/338190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11791207">Gao et al. (2002)</a> identified the CLN6 gene on chromosome 15q21-q23. <a href="#5" class="mim-tip-reference" title="Bronson, R. T., Donahue, L. R., Johnson, K. R., Tanner, A., Lane, P. W., Faust, J. R. <strong>Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9.</strong> Am. J. Med. Genet. 77: 289-297, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600738</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19980526)77:4<289::aid-ajmg8>3.0.co;2-i" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600738">Bronson et al. (1998)</a> demonstrated that the mouse Cln6 gene is on chromosome 9 in a region showing syntenic homology with human 15q21-q23. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9600738+11791207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By analyzing the isolated lysosome-enriched fractions from the livers of Cln6 -/- mice, <a href="#2" class="mim-tip-reference" title="Bajaj, L., Sharma, J., di Ronza, A., Zhang, P., Eblimit, A., Pal, R., Roman, D., Collette, J. R., Booth, C., Chang, K. T., Sifers, R. N., Jung, S. Y., Weimer, J. M., Chen, R., Schekman, R. W., Sardiello, M. <strong>A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer.</strong> J. Clin. Invest. 130: 4118-4132, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32597833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32597833</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32597833[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/10.1172/JCI130955" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32597833">Bajaj et al. (2020)</a> showed that Cln6 deficiency resulted in the depletion of various lysosomal enzymes from the lysosomal compartment, and that the cause of the lysosomal enzyme depletion was posttranslational. Bimolecular fluorescence complementation (BiFC) assays revealed that Cln6 interacted with Cln8 (<a href="/entry/607837">607837</a>) in the ER and did not traffic to the Golgi complex. Cln8 is localized to the ER and the ER-Golgi intermediate compartment; Cln8 trafficking to the Golgi was found to be uncoupled from its interaction with Cln6. Immunoprecipitation analysis showed that Cln6 also interacted with lysosomal enzymes. The interaction required the second luminal loop of Cln6, and Cln6 and Cln8 were mutually necessary for their interaction with lysosomal enzymes. Cln6 and Cln8 functioned as obligate partners in the recruitment of newly synthesized lysosomal enzymes in the ER, but the subsequent transfer of enzymes to the Golgi was mediated by Cln8 only. Analysis with Cln6 and Cln8 single- or double-knockout mice indicated that Cln6 and Cln8 worked as a functional unit in vivo, as loss of Cln6 did not aggravate pathology of Cln8-deficient mice and vice vera. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32597833" 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><strong><em>Neuronal Ceroid Lipofuscinosis 6A</em></strong></p><p>
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By sequence analysis, <a href="#8" class="mim-tip-reference" title="Gao, H., Boustany, R.-M. N., Espinola, J. A., Cotman, S. L., Srinidhi, L., Antonellis, K. A., Gillis, T., Qin, X., Liu, S., Donahue, L. R., Bronson, R. T., Faust, J. R., Stout, D., Haines, J. L., Lerner, T. J., MacDonald, M. E. <strong>Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.</strong> Am. J. Hum. Genet. 70: 324-335, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11791207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11791207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11791207[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/10.1086/338190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11791207">Gao et al. (2002)</a> identified homozygosity for mutations in the CLN6 gene in affected members of 2 families with variant late infantile CLN (CLN6A; <a href="/entry/601780">601780</a>): a G-to-T transversion in exon 3 in a Costa Rican family (<a href="#0001">606725.0001</a>) and a codon deletion in exon 5 in a Venezuelan family (<a href="#0002">606725.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11791207" 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="#14" class="mim-tip-reference" title="Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E. <strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong> Am. J. Hum. Genet. 70: 537-542, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11727201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11727201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11727201[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/10.1086/338708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11727201">Wheeler et al. (2002)</a> independently and simultaneously identified 6 different mutations in the CLN6 gene in patients with a variant form of late infantile CLN (CLN6A). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11727201" 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="Sharp, J. D., Wheeler, R. B., Parker, K. A., Gardiner, R. M., Williams, R. E., Mole, S. E. <strong>Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis.</strong> Hum. Mutat. 22: 35-42, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12815591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12815591</a>] [<a href="https://doi.org/10.1002/humu.10227" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12815591">Sharp et al. (2003)</a> identified 8 mutations in the CLN6 gene in patients with CLN6A, bringing to 18 the total number of CLN6 mutations found in this disorder. Ten mutations affected single amino acids, all of which are conserved across the vertebrate species. Minor differences in the pattern of disease symptom evolution could be identified. One patient with a more protected disease course was a compound heterozygote for a missense mutation and an unidentified mutation. Fifteen mutations occurred in 1 or 2 families only, and families from the same country did not all share the same mutation. No major founder mutation was identified, but the glu72-to-ter mutation (<a href="#0001">606725.0001</a>) was significantly more common in patients in Costa Rica than 2 other mutations present in that same population. A group of Roma Gypsy families from the Czech Republic shared 2 disease associated haplotypes, 1 of which is also present in a Pakistani family, consistent with the proposed migration of the Roma from the Indian subcontinent 1,000 years ago. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12815591" 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 2 sibs and an unrelated patient with CLN6A without visual impairment, <a href="#7" class="mim-tip-reference" title="Chin, J. J., Behnam, B., Davids, M., Sharma, P., Zein, W. M., Wang, C., Chepa-Lotrea, X., Gallantine, W. B., Toro, C., Adams, D. R. Tifft, C. J., Gahl, W. A., Malicdan, M. C. V. <strong>Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients.</strong> Molec. Genet. Metab. 126: 188-195, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30528883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30528883</a>] [<a href="https://doi.org/10.1016/j.ymgme.2018.12.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30528883">Chin et al. (2019)</a> identified homozygous and compound heterozygous mutations in the CLN6 gene (<a href="#0015">606725.0015</a>-<a href="#0017">606725.0017</a>), respectively. The mutations were found by whole-exome sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30528883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Neuronal Ceroid Lipofuscinosis 6B (Kufs Type)</em></strong></p><p>
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By genomewide mapping followed by candidate gene sequencing in 3 families with autosomal recessive neuronal ceroid lipofuscinosis (CLN6B; <a href="/entry/204300">204300</a>), <a href="#1" class="mim-tip-reference" title="Arsov, T., Smith, K. R., Damiano, J., Franceschetti, S., Canafoglia, L., Bromhead, C. J., Andermann, E., Vears, D. F., Cossette, P., Rajagopalan, S., McDougall, A., Sofia, V., and 10 others. <strong>Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.</strong> Am. J. Hum. Genet. 88: 566-573, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549341[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/10.1016/j.ajhg.2011.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549341">Arsov et al. (2011)</a> identified homozygous or compound heterozygous mutations in the CLN6 gene (see, e.g., <a href="#0011">606725.0011</a>-<a href="#0014">606725.0014</a>). Mutations were also found in affected members from 4 additional families with Kufs disease, yielding a total of 9 different pathogenic mutations in the CLN6 gene. All patients in the 7 families presented with progressive myoclonic epilepsy followed by dementia, consistent with a type A Kufs phenotype. There were no apparent genotype/phenotype correlations. Mutation in the CLN6 gene was not found in 1 family with a type B Kufs phenotype. <a href="#1" class="mim-tip-reference" title="Arsov, T., Smith, K. R., Damiano, J., Franceschetti, S., Canafoglia, L., Bromhead, C. J., Andermann, E., Vears, D. F., Cossette, P., Rajagopalan, S., McDougall, A., Sofia, V., and 10 others. <strong>Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.</strong> Am. J. Hum. Genet. 88: 566-573, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549341[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/10.1016/j.ajhg.2011.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549341">Arsov et al. (2011)</a> noted the striking phenotypic differences between patients with earlier onset CLN and patients with Kufs disease. Patients with CLN6A have retinal involvement, whereas none of the Kufs disease patients had retinal involvement. The authors suggested that Kufs disease patients may have some residual mutant protein function or that there are other disease modifiers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21549341" 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 13 unrelated families with CLN6B, <a href="#4" class="mim-tip-reference" title="Berkovic, S. F., Oliver, K. L., Canafoglia, L. Krieger, P., Damiano, J. A., Hildebrand, M. S., Morbin, M., Vears, D. F., Sofia, V., Giuliano, L., Garavaglia, B., Simonati, A., and 19 others. <strong>Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features.</strong> Brain 142: 59-69, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30561534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30561534</a>] [<a href="https://doi.org/10.1093/brain/awy297" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30561534">Berkovic et al. (2019)</a> identified homozygous CLN6 variants in 4 families and compound heterozygous variants in 9. Most pathogenic variants were predicted to result in amino acid substitutions; however, there were 4 heterozygous pathogenic variants predicting protein truncations, including 2 small deletions and/or insertions (indels), 1 large deletion, and 1 canonical splice site change. Compared to variants reported in the variant late infantile form (see <a href="/entry/601780">601780</a>), fewer variants predicted protein truncation. Certain heterozygous missense variants in the same amino acid position were found in both the variant late infantile form and adult-onset Kufs disease; whether onset was in late infancy or adulthood depended on the mutation severity of the second allele. Of the 13 families, 9 were of Italian ancestry. The authors noted that this was likely a product of these rare pathogenic variants being founder mutations in mainland Italy, Sicily, and Malta. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30561534" 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>Both <a href="#8" class="mim-tip-reference" title="Gao, H., Boustany, R.-M. N., Espinola, J. A., Cotman, S. L., Srinidhi, L., Antonellis, K. A., Gillis, T., Qin, X., Liu, S., Donahue, L. R., Bronson, R. T., Faust, J. R., Stout, D., Haines, J. L., Lerner, T. J., MacDonald, M. E. <strong>Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.</strong> Am. J. Hum. Genet. 70: 324-335, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11791207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11791207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11791207[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/10.1086/338190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11791207">Gao et al. (2002)</a> and <a href="#14" class="mim-tip-reference" title="Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E. <strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong> Am. J. Hum. Genet. 70: 537-542, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11727201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11727201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11727201[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/10.1086/338708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11727201">Wheeler et al. (2002)</a> identified mutations in the Cln6 gene in the nclf mouse, which manifests a recessive NCL-like disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11727201+11791207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Kielar, C., Wishart, T. M., Palmer, A., Dihanich, S., Wong, A. M., Macauley, S. L., Chan, C.-H., Sands, M. S., Pearce, D. A., Cooper, J. D., Gillingwater, T. H. <strong>Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease.</strong> Hum. Molec. Genet. 18: 4066-4080, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19640925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19640925</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19640925[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/ddp355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19640925">Kielar et al. (2009)</a> reported a progressive breakdown of axons and synapses in the brains of 2 different mouse models of NCL: the Ppt1 (<a href="/entry/600722">600722</a>)-null mouse model of infantile NCL (CLN1; <a href="/entry/256730">256730</a>) and the nclf mouse model of late infantile NCL. Synaptic pathology was evident in the thalamus and cortex of these mice, but occurred much earlier within the thalamus. Quantitative comparisons of expression levels for a subset of proteins previously implicated in regulation of axonal and synaptic vulnerability revealed changes in proteins involved with synaptic function/stability and cell-cycle regulation in both strains of NCL mice. Protein expression changes were present at pre/early-symptomatic stages, occurring in advance of morphologically detectable synaptic or axonal pathology and again displayed regional selectivity, occurring first within the thalamus and only later in the cortex. Although significant differences in individual protein expression profiles existed between the 2 NCL mouse models studied, 2 of the 15 proteins examined Vdac1 (<a href="/entry/604492">604492</a>) and Pttg1 (<a href="/entry/604147">604147</a>) displayed robust and significant changes at pre/early-symptomatic time-points in both strains of NCL mice. <a href="#9" class="mim-tip-reference" title="Kielar, C., Wishart, T. M., Palmer, A., Dihanich, S., Wong, A. M., Macauley, S. L., Chan, C.-H., Sands, M. S., Pearce, D. A., Cooper, J. D., Gillingwater, T. H. <strong>Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease.</strong> Hum. Molec. Genet. 18: 4066-4080, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19640925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19640925</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19640925[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/ddp355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19640925">Kielar et al. (2009)</a> concluded that synapses and axons are important early pathologic targets in the NCLs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19640925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a Costa Rican family with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>), <a href="#8" class="mim-tip-reference" title="Gao, H., Boustany, R.-M. N., Espinola, J. A., Cotman, S. L., Srinidhi, L., Antonellis, K. A., Gillis, T., Qin, X., Liu, S., Donahue, L. R., Bronson, R. T., Faust, J. R., Stout, D., Haines, J. L., Lerner, T. J., MacDonald, M. E. <strong>Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.</strong> Am. J. Hum. Genet. 70: 324-335, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11791207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11791207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11791207[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/10.1086/338190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11791207">Gao et al. (2002)</a> identified a G-to-T transversion at nucleotide 317 in exon 3 of the CLN6 gene, introducing a stop codon (E72X). The mutation was present in homozygous state. The same mutation was demonstrated in 6 Costa Rican kindreds by <a href="#14" class="mim-tip-reference" title="Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E. <strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong> Am. J. Hum. Genet. 70: 537-542, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11727201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11727201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11727201[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/10.1086/338708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11727201">Wheeler et al. (2002)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11727201+11791207" 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">rs121908079 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908079;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=rs121908079" 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=rs121908079" 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=RCV000004293" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004293" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004293</a>
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<p>In affected members of a Venezuelan family with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>), <a href="#8" class="mim-tip-reference" title="Gao, H., Boustany, R.-M. N., Espinola, J. A., Cotman, S. L., Srinidhi, L., Antonellis, K. A., Gillis, T., Qin, X., Liu, S., Donahue, L. R., Bronson, R. T., Faust, J. R., Stout, D., Haines, J. L., Lerner, T. J., MacDonald, M. E. <strong>Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.</strong> Am. J. Hum. Genet. 70: 324-335, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11791207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11791207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11791207[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/10.1086/338190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11791207">Gao et al. (2002)</a> identified homozygosity for a deletion of codon 171 (CTA) in exon 5 of the CLN6 gene, producing loss of tyr171 from the protein product. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11791207" 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 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</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">rs104894484 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894484;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=rs104894484" 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=rs104894484" 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=RCV000004294 OR RCV001851638 OR RCV002468959 OR RCV005007822" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004294, RCV001851638, RCV002468959, RCV005007822" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004294...</a>
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<p>In a Costa Rican family, <a href="#14" class="mim-tip-reference" title="Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E. <strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong> Am. J. Hum. Genet. 70: 537-542, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11727201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11727201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11727201[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/10.1086/338708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11727201">Wheeler et al. (2002)</a> found that variant neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>) was associated with a 368G-A transition in the CLN6 gene, resulting in a gly123-to-asp (G123D) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11727201" 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 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</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">rs786205065 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205065;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=rs786205065" 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=rs786205065" 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=RCV000004295" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004295" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004295</a>
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<p>In a family from Greece, <a href="#14" class="mim-tip-reference" title="Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E. <strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong> Am. J. Hum. Genet. 70: 537-542, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11727201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11727201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11727201[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/10.1086/338708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11727201">Wheeler et al. (2002)</a> found that variant late infantile neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>) was due to homozygosity for a 1-bp deletion, 6delG, in the CLN6 gene. This caused a frameshift after glu2 with 29 extra amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11727201" 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>.0005 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
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CLN6, 1-BP INS, 316C
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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> rs397515352 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515352;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/rs397515352?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=rs397515352" 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=rs397515352" 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=RCV000004296 OR RCV001171902 OR RCV002512747 OR RCV005007823" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004296, RCV001171902, RCV002512747, RCV005007823" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004296...</a>
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<p>In 2 Pakistani families with variant late infantile neuronal ceroid lipofuscinosis (CLN6; <a href="/entry/601780">601780</a>), <a href="#14" class="mim-tip-reference" title="Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E. <strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong> Am. J. Hum. Genet. 70: 537-542, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11727201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11727201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11727201[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/10.1086/338708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11727201">Wheeler et al. (2002)</a> found homozygosity for a 1-bp insertion, 316insC, producing a frameshift after pro105 with 25 extra amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11727201" 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>.0006 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
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CLN6, 2-BP DEL, 395CT
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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> rs774543080 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs774543080;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/rs774543080?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=rs774543080" 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=rs774543080" 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=RCV000004297 OR RCV000187113 OR RCV000465745 OR RCV003156056 OR RCV003332996 OR RCV005007824" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004297, RCV000187113, RCV000465745, RCV003156056, RCV003332996, RCV005007824" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004297...</a>
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<p>In an Indian family with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>), <a href="#14" class="mim-tip-reference" title="Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E. <strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong> Am. J. Hum. Genet. 70: 537-542, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11727201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11727201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11727201[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/10.1086/338708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11727201">Wheeler et al. (2002)</a> found a 2-bp deletion, 395_396delCT, in the CLN6 gene. This caused a frameshift after asp131 with 17 extra amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11727201" 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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<strong>.0007 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
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CLN6, ILE154DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908080 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908080;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=rs121908080" 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=rs121908080" 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=RCV000004298 OR RCV000184041 OR RCV000989354 OR RCV001091349 OR RCV002251873 OR RCV002490306" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004298, RCV000184041, RCV000989354, RCV001091349, RCV002251873, RCV002490306" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004298...</a>
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<p>In a family from Portugal, <a href="#14" class="mim-tip-reference" title="Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E. <strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong> Am. J. Hum. Genet. 70: 537-542, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11727201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11727201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11727201[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/10.1086/338708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11727201">Wheeler et al. (2002)</a> found that variant late infantile neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>) was caused by a 3-bp deletion (460_462delATC) in exon 4 of the CLN6 gene, resulting in the loss of the ile154 codon (I154del). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11727201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Teixeira, C. A., Espinola, J., Huo, L., Kohlschutter, J., Persaud Sawin, D.-A., Minassian, B., Bessa, C. J. P., Guimaraes, A., Stephan, D. A., Sa Miranda, M. C., MacDonald, M. E., Gil Ribeiro, M., Boustany, R.-M. N. <strong>Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis.</strong> Hum. Mutat. 21: 502-508, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12673792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12673792</a>] [<a href="https://doi.org/10.1002/humu.10207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12673792">Teixeira et al. (2003)</a> concluded that the I154del mutation accounts for 81.25% of mutated CLN6 alleles in Portuguese patients with CLN6A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12673792" 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 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</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">rs104894486 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894486;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=rs104894486" 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=rs104894486" 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=RCV000004299" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004299" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004299</a>
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<p>In 2 Turkish sibs with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>), <a href="#12" class="mim-tip-reference" title="Siintola, E., Topcu, M., Kohlschutter, A., Salonen, T., Joensuu, T., Anttonen, A.-K., Lehesjoki, A.-E. <strong>Two novel CLN6 mutations in variant late-infantile neuronal ceroid lipofuscinosis patients of Turkish origin.</strong> Clin. Genet. 68: 167-173, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15996215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15996215</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00471.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15996215">Siintola et al. (2005)</a> identified a homozygous 663C-G transversion in exon 6 of the CLN6 gene, resulting in a tyr221-to-ter (Y221X) substitution. The mutation was not identified in 119 Turkish control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15996215" 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 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</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">rs786205066 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205066;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=rs786205066" 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=rs786205066" 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=RCV000004300 OR RCV002512748" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004300, RCV002512748" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004300...</a>
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<p>In a Turkish patient with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>), <a href="#12" class="mim-tip-reference" title="Siintola, E., Topcu, M., Kohlschutter, A., Salonen, T., Joensuu, T., Anttonen, A.-K., Lehesjoki, A.-E. <strong>Two novel CLN6 mutations in variant late-infantile neuronal ceroid lipofuscinosis patients of Turkish origin.</strong> Clin. Genet. 68: 167-173, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15996215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15996215</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2005.00471.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15996215">Siintola et al. (2005)</a> identified a homozygous G-to-T transversion in intron 5 of the CLN6 gene, resulting in frameshifts with premature termination of the protein and absence of a functional CLN6 protein. The mutation was not identified in 119 Turkish control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15996215" 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 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
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CLN6, 4-BP DUP, 267AACG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786205067 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205067;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=rs786205067" 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=rs786205067" 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=RCV000004301 OR RCV001201445" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004301, RCV001201445" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004301...</a>
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<p>In a patient of Irish, French, and Native American origin with neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>), <a href="#13" class="mim-tip-reference" title="Teixeira, C. A., Espinola, J., Huo, L., Kohlschutter, J., Persaud Sawin, D.-A., Minassian, B., Bessa, C. J. P., Guimaraes, A., Stephan, D. A., Sa Miranda, M. C., MacDonald, M. E., Gil Ribeiro, M., Boustany, R.-M. N. <strong>Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis.</strong> Hum. Mutat. 21: 502-508, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12673792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12673792</a>] [<a href="https://doi.org/10.1002/humu.10207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12673792">Teixeira et al. (2003)</a> identified a 4-bp duplication in exon 3 of the CLN6 gene (267_268insAACG), resulting in truncation of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12673792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 5 families with CLN6A, <a href="#10" class="mim-tip-reference" title="Moore, S. J., Buckley, D. J., MacMillan, A., Marshall, H. D., Steele, L., Ray, P. N., Nawaz, Z., Baskin, B., Frecker, M., Carr, S. M., Ives, E., Parfrey, P. S. <strong>The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland.</strong> Clin. Genet. 74: 213-222, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18684116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18684116</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01054.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18684116">Moore et al. (2008)</a> identified a homozygous 4-bp duplication, which they called 268_271dup, resulting in a frameshift and premature termination (Val91GlufsTer42). All the families were from the southern coast of Newfoundland, suggesting a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18684116" 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>.0011 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS 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">rs154774633 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs154774633;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=rs154774633" 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=rs154774633" 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=RCV000058909 OR RCV001787030" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000058909, RCV001787030" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000058909...</a>
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<p>In 2 Italian sibs with adult-onset neuronal ceroid lipofuscinosis-6B (CLN6B; <a href="/entry/204300">204300</a>), <a href="#1" class="mim-tip-reference" title="Arsov, T., Smith, K. R., Damiano, J., Franceschetti, S., Canafoglia, L., Bromhead, C. J., Andermann, E., Vears, D. F., Cossette, P., Rajagopalan, S., McDougall, A., Sofia, V., and 10 others. <strong>Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.</strong> Am. J. Hum. Genet. 88: 566-573, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549341[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/10.1016/j.ajhg.2011.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549341">Arsov et al. (2011)</a> identified compound heterozygosity for 2 mutations in the CLN6 gene: a 200T-C transition in exon 3, resulting in a leu67-to-pro (L67P) substitution, and a 308G-A transition in exon 4, resulting in an arg103-to-gln (R103Q; <a href="#0012">606725.0012</a>) substitution. Both mutations occurred in highly conserved residues and were not found in 360 control chromosomes. The patients had onset at ages 16 and 36 years, respectively. Features included action myoclonus, tonic-clonic seizures, and later onset of dementia; ataxia was not present. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21549341" 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>.0012 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS 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> rs154774634 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs154774634;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/rs154774634?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=rs154774634" 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=rs154774634" 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=RCV000058911 OR RCV000675061 OR RCV001378313 OR RCV001787031 OR RCV005003402" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000058911, RCV000675061, RCV001378313, RCV001787031, RCV005003402" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000058911...</a>
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<p>For discussion of the arg103-to-gln (R103Q) mutation in the CLN6 gene that was found in compound heterozygous state in patients with adult-onset neuronal ceroid lipofuscinosis-6B (CLN6B; <a href="/entry/204300">204300</a>) by <a href="#1" class="mim-tip-reference" title="Arsov, T., Smith, K. R., Damiano, J., Franceschetti, S., Canafoglia, L., Bromhead, C. J., Andermann, E., Vears, D. F., Cossette, P., Rajagopalan, S., McDougall, A., Sofia, V., and 10 others. <strong>Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.</strong> Am. J. Hum. Genet. 88: 566-573, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549341[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/10.1016/j.ajhg.2011.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549341">Arsov et al. (2011)</a>, see <a href="#0011">606725.0011</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21549341" 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="0013" class="mim-anchor"></a>
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<strong>.0013 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS TYPE)</strong>
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CLN6, LEU47PHE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs154774635 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs154774635;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=rs154774635" 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=rs154774635" 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=RCV000058907 OR RCV000675107 OR RCV001787032" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000058907, RCV000675107, RCV001787032" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000058907...</a>
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<p>In an Italian woman, born of consanguineous parents, with neuronal ceroid lipofuscinosis-6B (CLN6B; <a href="/entry/204300">204300</a>), <a href="#1" class="mim-tip-reference" title="Arsov, T., Smith, K. R., Damiano, J., Franceschetti, S., Canafoglia, L., Bromhead, C. J., Andermann, E., Vears, D. F., Cossette, P., Rajagopalan, S., McDougall, A., Sofia, V., and 10 others. <strong>Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.</strong> Am. J. Hum. Genet. 88: 566-573, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549341[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/10.1016/j.ajhg.2011.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549341">Arsov et al. (2011)</a> identified a homozygous 139C-T transition in exon 2 of the CLN6 gene, resulting in a leu47-to-phe (L47F) substitution at a highly conserved residue. The mutation was not found in 360 control chromosomes. The patient had onset of tonic-clonic seizures and massive myoclonus at age 28, followed by ataxia and dementia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21549341" 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="0014" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0014 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS TYPE)</strong>
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</span>
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</h4>
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CLN6, ARG6THR
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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> rs154774636 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs154774636;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/rs154774636?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=rs154774636" 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=rs154774636" 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=RCV000058915 OR RCV001787033" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000058915, RCV001787033" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000058915...</a>
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<p>In a Canadian woman with neuronal ceroid lipofuscinosis-6B (CLN6B; <a href="/entry/204300">204300</a>), previously reported by <a href="#3" class="mim-tip-reference" title="Berkovic, S. F., Carpenter, S., Andermann, F., Andermann, E., Wolfe, L. S. <strong>Kufs' disease: a critical reappraisal.</strong> Brain 111: 27-62, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3284607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3284607</a>] [<a href="https://doi.org/10.1093/brain/111.1.27" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3284607">Berkovic et al. (1988)</a>, <a href="#1" class="mim-tip-reference" title="Arsov, T., Smith, K. R., Damiano, J., Franceschetti, S., Canafoglia, L., Bromhead, C. J., Andermann, E., Vears, D. F., Cossette, P., Rajagopalan, S., McDougall, A., Sofia, V., and 10 others. <strong>Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.</strong> Am. J. Hum. Genet. 88: 566-573, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549341[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/10.1016/j.ajhg.2011.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549341">Arsov et al. (2011)</a> identified a homozygous 17G-C transversion in exon 1 of the CLN6 gene, resulting in an arg6-to-thr (R6T) substitution at a highly conserved residue. The mutation was not found in 360 control chromosomes. The patient had onset of tonic-clonic seizures at age 31, followed by myoclonus and dementia; ataxia was not present. <a href="#3" class="mim-tip-reference" title="Berkovic, S. F., Carpenter, S., Andermann, F., Andermann, E., Wolfe, L. S. <strong>Kufs' disease: a critical reappraisal.</strong> Brain 111: 27-62, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3284607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3284607</a>] [<a href="https://doi.org/10.1093/brain/111.1.27" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3284607">Berkovic et al. (1988)</a> reported that the parents and 3 younger sibs were unaffected. The patient had a deceased affected sister and a maternal aunt with seizures from the age of 17 years. Ancestors of both parents were from adjacent small towns in the Italian province of Frosinone. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3284607+21549341" 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="0015" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0015 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
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CLN6, 3-BP DUP, 218GGT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2141141533 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2141141533;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=rs2141141533" 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=rs2141141533" 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=RCV001543158" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001543158" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001543158</a>
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<p>In a 15-year-old girl (proband 1) with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780), <a href="#7" class="mim-tip-reference" title="Chin, J. J., Behnam, B., Davids, M., Sharma, P., Zein, W. M., Wang, C., Chepa-Lotrea, X., Gallantine, W. B., Toro, C., Adams, D. R. Tifft, C. J., Gahl, W. A., Malicdan, M. C. V. <strong>Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients.</strong> Molec. Genet. Metab. 126: 188-195, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30528883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30528883</a>] [<a href="https://doi.org/10.1016/j.ymgme.2018.12.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30528883">Chin et al. (2019)</a> identified compound heterozygous mutations in the CLN6 gene: a 3-bp duplication (c.218_220dupGGT), resulting in a duplication of tryptophan-73, and a c.296A-G transition, resulting in a lys99-to-arg (K99R; <a href="#0016">606725.0016</a>) substitution. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. The parents were shown to be mutation carriers. Analysis in patient fibroblasts showed that CLN6 mRNA expression was unaltered, and CLN6 protein expression was slightly increased. The patient had developmental regression, ataxia, and progressive myoclonic epilepsy, but no visual impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30528883" 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="0016" class="mim-anchor"></a>
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<h4>
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<strong>.0016 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
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CLN6, LYS99ARG
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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> rs146782642 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs146782642;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/rs146782642?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=rs146782642" 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=rs146782642" 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=RCV001543159 OR RCV002032545 OR RCV002568264 OR RCV005005956" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001543159, RCV002032545, RCV002568264, RCV005005956" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001543159...</a>
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<span class="mim-text-font">
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<p>For discussion of the c.296A-G transition in the CLN6 gene, resulting in a lys99-to-arg (K99R) substitution, that was found in compound heterozygous state in a patient with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; <a href="/entry/601780">601780</a>) by <a href="#7" class="mim-tip-reference" title="Chin, J. J., Behnam, B., Davids, M., Sharma, P., Zein, W. M., Wang, C., Chepa-Lotrea, X., Gallantine, W. B., Toro, C., Adams, D. R. Tifft, C. J., Gahl, W. A., Malicdan, M. C. V. <strong>Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients.</strong> Molec. Genet. Metab. 126: 188-195, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30528883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30528883</a>] [<a href="https://doi.org/10.1016/j.ymgme.2018.12.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30528883">Chin et al. (2019)</a>, see <a href="#0015">606725.0015</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30528883" 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>.0017 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</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> rs149262877 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs149262877;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/rs149262877?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=rs149262877" 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=rs149262877" 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=RCV001330791" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001330791" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001330791</a>
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<p>In a sister (proband 2) and brother with variant late infantile neuronal ceroid lipofuscinosis-6A (CLN6A; <a href="/entry/601780">601780</a>), <a href="#7" class="mim-tip-reference" title="Chin, J. J., Behnam, B., Davids, M., Sharma, P., Zein, W. M., Wang, C., Chepa-Lotrea, X., Gallantine, W. B., Toro, C., Adams, D. R. Tifft, C. J., Gahl, W. A., Malicdan, M. C. V. <strong>Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients.</strong> Molec. Genet. Metab. 126: 188-195, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30528883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30528883</a>] [<a href="https://doi.org/10.1016/j.ymgme.2018.12.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30528883">Chin et al. (2019)</a> identified homozygosity for a c.723G-T transversion in the CLN6 gene, resulting in a met241-to-ile (M241I) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. Analysis in fibroblasts from one of the sibs showed that mRNA expression was unaltered. CLN6 protein expression in the fibroblasts was slightly increased, with a significant increase in the monomeric form of CLN6, suggesting that the mutation may affect protein dimerization. The sibs had clinical features including developmental regression and ataxia, but no visual impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30528883" 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>.0018 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS TYPE)</strong>
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CLN6, ILE117SER
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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> rs752212030 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs752212030;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/rs752212030?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=rs752212030" 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=rs752212030" 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=RCV001787284" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001787284" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001787284</a>
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<p>In a 29-year-old woman with neuronal ceroid lipofuscinosis-6B (Kufs type) (CLN6B; <a href="/entry/204300">204300</a>), <a href="#6" class="mim-tip-reference" title="Cherian, A., K. P. D., Paramasivan, N. K., Krishnan, S. <strong>Pearls & oy-sters: levodopa-responsive adult NCL (type B Kufs) disease due to CLN6 mutation.</strong> Neurology 96: e2662-e2665, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33875558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33875558</a>] [<a href="https://doi.org/10.1212/WNL.0000000000011997" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33875558">Cherian et al. (2021)</a> identified a homozygous c.350T-G transversion in exon 4 of the CLN6 gene, resulting in an ile117-to-ser (I117S) substitution. The mutation was found by next-generation sequencing. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33875558" 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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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Arsov2011" class="mim-anchor"></a>
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Arsov, T., Smith, K. R., Damiano, J., Franceschetti, S., Canafoglia, L., Bromhead, C. J., Andermann, E., Vears, D. F., Cossette, P., Rajagopalan, S., McDougall, A., Sofia, V., and 10 others.
|
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<strong>Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.</strong>
|
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Am. J. Hum. Genet. 88: 566-573, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549341[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=21549341" 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/10.1016/j.ajhg.2011.04.004" target="_blank">Full Text</a>]
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Bajaj, L., Sharma, J., di Ronza, A., Zhang, P., Eblimit, A., Pal, R., Roman, D., Collette, J. R., Booth, C., Chang, K. T., Sifers, R. N., Jung, S. Y., Weimer, J. M., Chen, R., Schekman, R. W., Sardiello, M.
|
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<strong>A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer.</strong>
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J. Clin. Invest. 130: 4118-4132, 2020.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32597833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32597833</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32597833[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=32597833" 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/10.1172/JCI130955" target="_blank">Full Text</a>]
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<a id="Berkovic1988" class="mim-anchor"></a>
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Berkovic, S. F., Carpenter, S., Andermann, F., Andermann, E., Wolfe, L. S.
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<strong>Kufs' disease: a critical reappraisal.</strong>
|
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Brain 111: 27-62, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3284607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3284607</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3284607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/111.1.27" target="_blank">Full Text</a>]
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Berkovic, S. F., Oliver, K. L., Canafoglia, L. Krieger, P., Damiano, J. A., Hildebrand, M. S., Morbin, M., Vears, D. F., Sofia, V., Giuliano, L., Garavaglia, B., Simonati, A., and 19 others.
|
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<strong>Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features.</strong>
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Brain 142: 59-69, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30561534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30561534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30561534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awy297" target="_blank">Full Text</a>]
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Bronson, R. T., Donahue, L. R., Johnson, K. R., Tanner, A., Lane, P. W., Faust, J. R.
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<strong>Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9.</strong>
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Am. J. Med. Genet. 77: 289-297, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600738</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600738" 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/(sici)1096-8628(19980526)77:4<289::aid-ajmg8>3.0.co;2-i" target="_blank">Full Text</a>]
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<a id="Cherian2021" class="mim-anchor"></a>
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Cherian, A., K. P. D., Paramasivan, N. K., Krishnan, S.
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<strong>Pearls & oy-sters: levodopa-responsive adult NCL (type B Kufs) disease due to CLN6 mutation.</strong>
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Neurology 96: e2662-e2665, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33875558/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33875558</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33875558" 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.0000000000011997" target="_blank">Full Text</a>]
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<a id="Chin2019" class="mim-anchor"></a>
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Chin, J. J., Behnam, B., Davids, M., Sharma, P., Zein, W. M., Wang, C., Chepa-Lotrea, X., Gallantine, W. B., Toro, C., Adams, D. R. Tifft, C. J., Gahl, W. A., Malicdan, M. C. V.
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<strong>Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients.</strong>
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Molec. Genet. Metab. 126: 188-195, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30528883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30528883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30528883" 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/10.1016/j.ymgme.2018.12.001" target="_blank">Full Text</a>]
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Gao, H., Boustany, R.-M. N., Espinola, J. A., Cotman, S. L., Srinidhi, L., Antonellis, K. A., Gillis, T., Qin, X., Liu, S., Donahue, L. R., Bronson, R. T., Faust, J. R., Stout, D., Haines, J. L., Lerner, T. J., MacDonald, M. E.
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<strong>Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.</strong>
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Am. J. Hum. Genet. 70: 324-335, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11791207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11791207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11791207[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=11791207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/338190" 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="9" class="mim-anchor"></a>
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<a id="Kielar2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kielar, C., Wishart, T. M., Palmer, A., Dihanich, S., Wong, A. M., Macauley, S. L., Chan, C.-H., Sands, M. S., Pearce, D. A., Cooper, J. D., Gillingwater, T. H.
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|
<strong>Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease.</strong>
|
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Hum. Molec. Genet. 18: 4066-4080, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19640925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19640925</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19640925[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=19640925" 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/ddp355" 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="10" class="mim-anchor"></a>
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<a id="Moore2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Moore, S. J., Buckley, D. J., MacMillan, A., Marshall, H. D., Steele, L., Ray, P. N., Nawaz, Z., Baskin, B., Frecker, M., Carr, S. M., Ives, E., Parfrey, P. S.
|
|
<strong>The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland.</strong>
|
|
Clin. Genet. 74: 213-222, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18684116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18684116</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18684116" 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/10.1111/j.1399-0004.2008.01054.x" 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="11" class="mim-anchor"></a>
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<a id="Sharp2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sharp, J. D., Wheeler, R. B., Parker, K. A., Gardiner, R. M., Williams, R. E., Mole, S. E.
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|
<strong>Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis.</strong>
|
|
Hum. Mutat. 22: 35-42, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12815591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12815591</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12815591" 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.10227" 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="Siintola2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Siintola, E., Topcu, M., Kohlschutter, A., Salonen, T., Joensuu, T., Anttonen, A.-K., Lehesjoki, A.-E.
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<strong>Two novel CLN6 mutations in variant late-infantile neuronal ceroid lipofuscinosis patients of Turkish origin.</strong>
|
|
Clin. Genet. 68: 167-173, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15996215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15996215</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15996215" 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/10.1111/j.1399-0004.2005.00471.x" 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="13" class="mim-anchor"></a>
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<a id="Teixeira2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Teixeira, C. A., Espinola, J., Huo, L., Kohlschutter, J., Persaud Sawin, D.-A., Minassian, B., Bessa, C. J. P., Guimaraes, A., Stephan, D. A., Sa Miranda, M. C., MacDonald, M. E., Gil Ribeiro, M., Boustany, R.-M. N.
|
|
<strong>Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis.</strong>
|
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Hum. Mutat. 21: 502-508, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12673792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12673792</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12673792" 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.10207" 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="14" class="mim-anchor"></a>
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<a id="Wheeler2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E.
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<strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong>
|
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Am. J. Hum. Genet. 70: 537-542, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11727201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11727201</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11727201[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=11727201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/338708" 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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Bao Lige - updated : 07/03/2024
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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 : 12/01/2021<br>Cassandra L. Kniffin - updated : 12/01/2021<br>Hilary J. Vernon - updated : 07/22/2021<br>Sonja A. Rasmussen - updated : 02/19/2019<br>Cassandra L. Kniffin - updated : 5/16/2011<br>George E. Tiller - updated : 9/30/2010<br>Cassandra L. Kniffin - updated : 5/1/2009<br>Cassandra L. Kniffin - updated : 3/16/2006<br>Victor A. McKusick - updated : 8/18/2003<br>Victor A. McKusick - updated : 6/11/2003<br>Carol A. Bocchini - updated : 2/27/2002
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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 : 2/27/2002
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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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alopez : 07/03/2024
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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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carol : 03/17/2022<br>carol : 12/01/2021<br>ckniffin : 12/01/2021<br>carol : 07/26/2021<br>carol : 07/22/2021<br>carol : 08/11/2020<br>carol : 02/19/2019<br>carol : 05/14/2015<br>mcolton : 5/4/2015<br>carol : 10/3/2013<br>wwang : 5/17/2011<br>ckniffin : 5/16/2011<br>wwang : 10/13/2010<br>terry : 9/30/2010<br>wwang : 5/11/2009<br>ckniffin : 5/1/2009<br>carol : 3/23/2006<br>ckniffin : 3/21/2006<br>ckniffin : 3/16/2006<br>cwells : 8/21/2003<br>terry : 8/18/2003<br>carol : 6/12/2003<br>terry : 6/11/2003<br>alopez : 5/16/2002<br>cwells : 2/27/2002<br>carol : 2/27/2002
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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> 606725
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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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CLN6 TRANSMEMBRANE ER PROTEIN; CLN6
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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-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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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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CLN6 GENE
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</span>
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</h4>
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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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<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: CLN6</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>
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<em>
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Cytogenetic location: 15q23
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Genomic coordinates <span class="small">(GRCh38)</span> : 15:68,206,992-68,257,211 </span>
|
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</em>
|
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</strong>
|
|
<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>
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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="2">
|
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<span class="mim-font">
|
|
15q23
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Ceroid lipofuscinosis, neuronal, 6A
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
601780
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
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</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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<tr>
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<td>
|
|
<span class="mim-font">
|
|
Ceroid lipofuscinosis, neuronal, 6B (Kufs type)
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
204300
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
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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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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<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">
|
|
<p>By positional cloning in the candidate region for variant late infantile neuronal ceroid lipofuscinosis (vLINCL, CLN6A; 601780) on chromosome 15q21-q23, Gao et al. (2002) identified the CLN6 (FLJ0561) gene. CLN6 encodes a deduced 311-amino acid protein with 7 predicted transmembrane domains and a predicted molecular mass of 36 kD. Northern blot analysis detected expression of a major 2.4-kb CLN6 mRNA in adult and embryonic brain and in peripheral tissues of mouse and human. The protein is conserved across vertebrates. </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">
|
|
<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>Gao et al. (2002) determined that the CLN6 gene contains 7 exons that span approximately 23 kb of genomic DNA. </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>By sequence analysis, Gao et al. (2002) identified the CLN6 gene on chromosome 15q21-q23. Bronson et al. (1998) demonstrated that the mouse Cln6 gene is on chromosome 9 in a region showing syntenic homology with human 15q21-q23. </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>By analyzing the isolated lysosome-enriched fractions from the livers of Cln6 -/- mice, Bajaj et al. (2020) showed that Cln6 deficiency resulted in the depletion of various lysosomal enzymes from the lysosomal compartment, and that the cause of the lysosomal enzyme depletion was posttranslational. Bimolecular fluorescence complementation (BiFC) assays revealed that Cln6 interacted with Cln8 (607837) in the ER and did not traffic to the Golgi complex. Cln8 is localized to the ER and the ER-Golgi intermediate compartment; Cln8 trafficking to the Golgi was found to be uncoupled from its interaction with Cln6. Immunoprecipitation analysis showed that Cln6 also interacted with lysosomal enzymes. The interaction required the second luminal loop of Cln6, and Cln6 and Cln8 were mutually necessary for their interaction with lysosomal enzymes. Cln6 and Cln8 functioned as obligate partners in the recruitment of newly synthesized lysosomal enzymes in the ER, but the subsequent transfer of enzymes to the Golgi was mediated by Cln8 only. Analysis with Cln6 and Cln8 single- or double-knockout mice indicated that Cln6 and Cln8 worked as a functional unit in vivo, as loss of Cln6 did not aggravate pathology of Cln8-deficient mice and vice vera. </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">
|
|
<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><strong><em>Neuronal Ceroid Lipofuscinosis 6A</em></strong></p><p>
|
|
By sequence analysis, Gao et al. (2002) identified homozygosity for mutations in the CLN6 gene in affected members of 2 families with variant late infantile CLN (CLN6A; 601780): a G-to-T transversion in exon 3 in a Costa Rican family (606725.0001) and a codon deletion in exon 5 in a Venezuelan family (606725.0002). </p><p>Wheeler et al. (2002) independently and simultaneously identified 6 different mutations in the CLN6 gene in patients with a variant form of late infantile CLN (CLN6A). </p><p>Sharp et al. (2003) identified 8 mutations in the CLN6 gene in patients with CLN6A, bringing to 18 the total number of CLN6 mutations found in this disorder. Ten mutations affected single amino acids, all of which are conserved across the vertebrate species. Minor differences in the pattern of disease symptom evolution could be identified. One patient with a more protected disease course was a compound heterozygote for a missense mutation and an unidentified mutation. Fifteen mutations occurred in 1 or 2 families only, and families from the same country did not all share the same mutation. No major founder mutation was identified, but the glu72-to-ter mutation (606725.0001) was significantly more common in patients in Costa Rica than 2 other mutations present in that same population. A group of Roma Gypsy families from the Czech Republic shared 2 disease associated haplotypes, 1 of which is also present in a Pakistani family, consistent with the proposed migration of the Roma from the Indian subcontinent 1,000 years ago. </p><p>In 2 sibs and an unrelated patient with CLN6A without visual impairment, Chin et al. (2019) identified homozygous and compound heterozygous mutations in the CLN6 gene (606725.0015-606725.0017), respectively. The mutations were found by whole-exome sequencing. </p><p><strong><em>Neuronal Ceroid Lipofuscinosis 6B (Kufs Type)</em></strong></p><p>
|
|
By genomewide mapping followed by candidate gene sequencing in 3 families with autosomal recessive neuronal ceroid lipofuscinosis (CLN6B; 204300), Arsov et al. (2011) identified homozygous or compound heterozygous mutations in the CLN6 gene (see, e.g., 606725.0011-606725.0014). Mutations were also found in affected members from 4 additional families with Kufs disease, yielding a total of 9 different pathogenic mutations in the CLN6 gene. All patients in the 7 families presented with progressive myoclonic epilepsy followed by dementia, consistent with a type A Kufs phenotype. There were no apparent genotype/phenotype correlations. Mutation in the CLN6 gene was not found in 1 family with a type B Kufs phenotype. Arsov et al. (2011) noted the striking phenotypic differences between patients with earlier onset CLN and patients with Kufs disease. Patients with CLN6A have retinal involvement, whereas none of the Kufs disease patients had retinal involvement. The authors suggested that Kufs disease patients may have some residual mutant protein function or that there are other disease modifiers. </p><p>In 13 unrelated families with CLN6B, Berkovic et al. (2019) identified homozygous CLN6 variants in 4 families and compound heterozygous variants in 9. Most pathogenic variants were predicted to result in amino acid substitutions; however, there were 4 heterozygous pathogenic variants predicting protein truncations, including 2 small deletions and/or insertions (indels), 1 large deletion, and 1 canonical splice site change. Compared to variants reported in the variant late infantile form (see 601780), fewer variants predicted protein truncation. Certain heterozygous missense variants in the same amino acid position were found in both the variant late infantile form and adult-onset Kufs disease; whether onset was in late infancy or adulthood depended on the mutation severity of the second allele. Of the 13 families, 9 were of Italian ancestry. The authors noted that this was likely a product of these rare pathogenic variants being founder mutations in mainland Italy, Sicily, and Malta. </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">
|
|
<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">
|
|
<p>Both Gao et al. (2002) and Wheeler et al. (2002) identified mutations in the Cln6 gene in the nclf mouse, which manifests a recessive NCL-like disease. </p><p>Kielar et al. (2009) reported a progressive breakdown of axons and synapses in the brains of 2 different mouse models of NCL: the Ppt1 (600722)-null mouse model of infantile NCL (CLN1; 256730) and the nclf mouse model of late infantile NCL. Synaptic pathology was evident in the thalamus and cortex of these mice, but occurred much earlier within the thalamus. Quantitative comparisons of expression levels for a subset of proteins previously implicated in regulation of axonal and synaptic vulnerability revealed changes in proteins involved with synaptic function/stability and cell-cycle regulation in both strains of NCL mice. Protein expression changes were present at pre/early-symptomatic stages, occurring in advance of morphologically detectable synaptic or axonal pathology and again displayed regional selectivity, occurring first within the thalamus and only later in the cortex. Although significant differences in individual protein expression profiles existed between the 2 NCL mouse models studied, 2 of the 15 proteins examined Vdac1 (604492) and Pttg1 (604147) displayed robust and significant changes at pre/early-symptomatic time-points in both strains of NCL mice. Kielar et al. (2009) concluded that synapses and axons are important early pathologic targets in the NCLs. </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>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
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</span>
|
|
<strong>18 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>
|
|
<span class="mim-font">
|
|
<strong>.0001 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
CLN6, GLU72TER
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<br />
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|
|
SNP: rs104894483,
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|
|
gnomAD: rs104894483,
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|
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|
|
|
ClinVar: RCV000004292, RCV000492979, RCV001067723, RCV002316185, RCV005003333
|
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|
|
|
</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Costa Rican family with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780), Gao et al. (2002) identified a G-to-T transversion at nucleotide 317 in exon 3 of the CLN6 gene, introducing a stop codon (E72X). The mutation was present in homozygous state. The same mutation was demonstrated in 6 Costa Rican kindreds by Wheeler et al. (2002). </p>
|
|
</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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|
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</div>
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|
<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
CLN6, TYR171DEL
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|
|
<br />
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|
|
|
SNP: rs121908079,
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|
|
|
|
|
|
|
ClinVar: RCV000004293
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a Venezuelan family with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780), Gao et al. (2002) identified homozygosity for a deletion of codon 171 (CTA) in exon 5 of the CLN6 gene, producing loss of tyr171 from the protein product. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, GLY123ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894484,
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|
|
|
|
|
|
|
ClinVar: RCV000004294, RCV001851638, RCV002468959, RCV005007822
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Costa Rican family, Wheeler et al. (2002) found that variant neuronal ceroid lipofuscinosis (CLN6A; 601780) was associated with a 368G-A transition in the CLN6 gene, resulting in a gly123-to-asp (G123D) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, 1-BP DEL, 6G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786205065,
|
|
|
|
|
|
|
|
ClinVar: RCV000004295
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family from Greece, Wheeler et al. (2002) found that variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780) was due to homozygosity for a 1-bp deletion, 6delG, in the CLN6 gene. This caused a frameshift after glu2 with 29 extra amino acids. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, 1-BP INS, 316C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397515352,
|
|
|
|
|
|
gnomAD: rs397515352,
|
|
|
|
|
|
ClinVar: RCV000004296, RCV001171902, RCV002512747, RCV005007823
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Pakistani families with variant late infantile neuronal ceroid lipofuscinosis (CLN6; 601780), Wheeler et al. (2002) found homozygosity for a 1-bp insertion, 316insC, producing a frameshift after pro105 with 25 extra amino acids. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, 2-BP DEL, 395CT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs774543080,
|
|
|
|
|
|
gnomAD: rs774543080,
|
|
|
|
|
|
ClinVar: RCV000004297, RCV000187113, RCV000465745, RCV003156056, RCV003332996, RCV005007824
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Indian family with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780), Wheeler et al. (2002) found a 2-bp deletion, 395_396delCT, in the CLN6 gene. This caused a frameshift after asp131 with 17 extra amino acids. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, ILE154DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908080,
|
|
|
|
|
|
|
|
ClinVar: RCV000004298, RCV000184041, RCV000989354, RCV001091349, RCV002251873, RCV002490306
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family from Portugal, Wheeler et al. (2002) found that variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780) was caused by a 3-bp deletion (460_462delATC) in exon 4 of the CLN6 gene, resulting in the loss of the ile154 codon (I154del). </p><p>Teixeira et al. (2003) concluded that the I154del mutation accounts for 81.25% of mutated CLN6 alleles in Portuguese patients with CLN6A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, TYR221TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894486,
|
|
|
|
|
|
|
|
ClinVar: RCV000004299
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Turkish sibs with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780), Siintola et al. (2005) identified a homozygous 663C-G transversion in exon 6 of the CLN6 gene, resulting in a tyr221-to-ter (Y221X) substitution. The mutation was not identified in 119 Turkish control chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, IVS5DS, G-T, +5
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786205066,
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|
|
|
|
|
|
|
ClinVar: RCV000004300, RCV002512748
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Turkish patient with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780), Siintola et al. (2005) identified a homozygous G-to-T transversion in intron 5 of the CLN6 gene, resulting in frameshifts with premature termination of the protein and absence of a functional CLN6 protein. The mutation was not identified in 119 Turkish control chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, 4-BP DUP, 267AACG
|
|
|
|
|
|
<br />
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|
|
SNP: rs786205067,
|
|
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|
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|
|
ClinVar: RCV000004301, RCV001201445
|
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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>In a patient of Irish, French, and Native American origin with neuronal ceroid lipofuscinosis (CLN6A; 601780), Teixeira et al. (2003) identified a 4-bp duplication in exon 3 of the CLN6 gene (267_268insAACG), resulting in truncation of the protein. </p><p>In affected members of 5 families with CLN6A, Moore et al. (2008) identified a homozygous 4-bp duplication, which they called 268_271dup, resulting in a frameshift and premature termination (Val91GlufsTer42). All the families were from the southern coast of Newfoundland, suggesting a founder effect. </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>.0011 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
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<span class="mim-text-font">
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CLN6, LEU67PRO
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<br />
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SNP: rs154774633,
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ClinVar: RCV000058909, RCV001787030
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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 Italian sibs with adult-onset neuronal ceroid lipofuscinosis-6B (CLN6B; 204300), Arsov et al. (2011) identified compound heterozygosity for 2 mutations in the CLN6 gene: a 200T-C transition in exon 3, resulting in a leu67-to-pro (L67P) substitution, and a 308G-A transition in exon 4, resulting in an arg103-to-gln (R103Q; 606725.0012) substitution. Both mutations occurred in highly conserved residues and were not found in 360 control chromosomes. The patients had onset at ages 16 and 36 years, respectively. Features included action myoclonus, tonic-clonic seizures, and later onset of dementia; ataxia was not present. </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>
|
|
<span class="mim-font">
|
|
<strong>.0012 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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CLN6, ARG103GLN
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<br />
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SNP: rs154774634,
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|
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gnomAD: rs154774634,
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|
|
ClinVar: RCV000058911, RCV000675061, RCV001378313, RCV001787031, RCV005003402
|
|
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|
|
|
</span>
|
|
</div>
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|
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<div>
|
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<span class="mim-text-font">
|
|
<p>For discussion of the arg103-to-gln (R103Q) mutation in the CLN6 gene that was found in compound heterozygous state in patients with adult-onset neuronal ceroid lipofuscinosis-6B (CLN6B; 204300) by Arsov et al. (2011), see 606725.0011. </p>
|
|
</span>
|
|
</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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
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|
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CLN6, LEU47PHE
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<br />
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|
|
SNP: rs154774635,
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|
|
|
|
|
ClinVar: RCV000058907, RCV000675107, RCV001787032
|
|
|
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|
|
</span>
|
|
</div>
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|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian woman, born of consanguineous parents, with neuronal ceroid lipofuscinosis-6B (CLN6B; 204300), Arsov et al. (2011) identified a homozygous 139C-T transition in exon 2 of the CLN6 gene, resulting in a leu47-to-phe (L47F) substitution at a highly conserved residue. The mutation was not found in 360 control chromosomes. The patient had onset of tonic-clonic seizures and massive myoclonus at age 28, followed by ataxia and dementia. </p>
|
|
</span>
|
|
</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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|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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CLN6, ARG6THR
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<br />
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|
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SNP: rs154774636,
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|
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|
|
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gnomAD: rs154774636,
|
|
|
|
|
|
ClinVar: RCV000058915, RCV001787033
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Canadian woman with neuronal ceroid lipofuscinosis-6B (CLN6B; 204300), previously reported by Berkovic et al. (1988), Arsov et al. (2011) identified a homozygous 17G-C transversion in exon 1 of the CLN6 gene, resulting in an arg6-to-thr (R6T) substitution at a highly conserved residue. The mutation was not found in 360 control chromosomes. The patient had onset of tonic-clonic seizures at age 31, followed by myoclonus and dementia; ataxia was not present. Berkovic et al. (1988) reported that the parents and 3 younger sibs were unaffected. The patient had a deceased affected sister and a maternal aunt with seizures from the age of 17 years. Ancestors of both parents were from adjacent small towns in the Italian province of Frosinone. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
|
|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, 3-BP DUP, 218GGT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2141141533,
|
|
|
|
|
|
|
|
ClinVar: RCV001543158
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old girl (proband 1) with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780), Chin et al. (2019) identified compound heterozygous mutations in the CLN6 gene: a 3-bp duplication (c.218_220dupGGT), resulting in a duplication of tryptophan-73, and a c.296A-G transition, resulting in a lys99-to-arg (K99R; 606725.0016) substitution. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. The parents were shown to be mutation carriers. Analysis in patient fibroblasts showed that CLN6 mRNA expression was unaltered, and CLN6 protein expression was slightly increased. The patient had developmental regression, ataxia, and progressive myoclonic epilepsy, but no visual impairment. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, LYS99ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs146782642,
|
|
|
|
|
|
gnomAD: rs146782642,
|
|
|
|
|
|
ClinVar: RCV001543159, RCV002032545, RCV002568264, RCV005005956
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.296A-G transition in the CLN6 gene, resulting in a lys99-to-arg (K99R) substitution, that was found in compound heterozygous state in a patient with variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780) by Chin et al. (2019), see 606725.0015. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 CEROID LIPOFUSCINOSIS, NEURONAL, 6A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, MET241ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs149262877,
|
|
|
|
|
|
gnomAD: rs149262877,
|
|
|
|
|
|
ClinVar: RCV001330791
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sister (proband 2) and brother with variant late infantile neuronal ceroid lipofuscinosis-6A (CLN6A; 601780), Chin et al. (2019) identified homozygosity for a c.723G-T transversion in the CLN6 gene, resulting in a met241-to-ile (M241I) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. Analysis in fibroblasts from one of the sibs showed that mRNA expression was unaltered. CLN6 protein expression in the fibroblasts was slightly increased, with a significant increase in the monomeric form of CLN6, suggesting that the mutation may affect protein dimerization. The sibs had clinical features including developmental regression and ataxia, but no visual impairment. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 CEROID LIPOFUSCINOSIS, NEURONAL, 6B (KUFS TYPE)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CLN6, ILE117SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs752212030,
|
|
|
|
|
|
gnomAD: rs752212030,
|
|
|
|
|
|
ClinVar: RCV001787284
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 29-year-old woman with neuronal ceroid lipofuscinosis-6B (Kufs type) (CLN6B; 204300), Cherian et al. (2021) identified a homozygous c.350T-G transversion in exon 4 of the CLN6 gene, resulting in an ile117-to-ser (I117S) substitution. The mutation was found by next-generation sequencing. Functional studies of the variant were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Arsov, T., Smith, K. R., Damiano, J., Franceschetti, S., Canafoglia, L., Bromhead, C. J., Andermann, E., Vears, D. F., Cossette, P., Rajagopalan, S., McDougall, A., Sofia, V., and 10 others.
|
|
<strong>Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.</strong>
|
|
Am. J. Hum. Genet. 88: 566-573, 2011.
|
|
|
|
|
|
[PubMed: 21549341]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2011.04.004]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bajaj, L., Sharma, J., di Ronza, A., Zhang, P., Eblimit, A., Pal, R., Roman, D., Collette, J. R., Booth, C., Chang, K. T., Sifers, R. N., Jung, S. Y., Weimer, J. M., Chen, R., Schekman, R. W., Sardiello, M.
|
|
<strong>A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer.</strong>
|
|
J. Clin. Invest. 130: 4118-4132, 2020.
|
|
|
|
|
|
[PubMed: 32597833]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI130955]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berkovic, S. F., Carpenter, S., Andermann, F., Andermann, E., Wolfe, L. S.
|
|
<strong>Kufs' disease: a critical reappraisal.</strong>
|
|
Brain 111: 27-62, 1988.
|
|
|
|
|
|
[PubMed: 3284607]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/111.1.27]
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berkovic, S. F., Oliver, K. L., Canafoglia, L. Krieger, P., Damiano, J. A., Hildebrand, M. S., Morbin, M., Vears, D. F., Sofia, V., Giuliano, L., Garavaglia, B., Simonati, A., and 19 others.
|
|
<strong>Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features.</strong>
|
|
Brain 142: 59-69, 2019.
|
|
|
|
|
|
[PubMed: 30561534]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awy297]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bronson, R. T., Donahue, L. R., Johnson, K. R., Tanner, A., Lane, P. W., Faust, J. R.
|
|
<strong>Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9.</strong>
|
|
Am. J. Med. Genet. 77: 289-297, 1998.
|
|
|
|
|
|
[PubMed: 9600738]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19980526)77:4<289::aid-ajmg8>3.0.co;2-i]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cherian, A., K. P. D., Paramasivan, N. K., Krishnan, S.
|
|
<strong>Pearls & oy-sters: levodopa-responsive adult NCL (type B Kufs) disease due to CLN6 mutation.</strong>
|
|
Neurology 96: e2662-e2665, 2021.
|
|
|
|
|
|
[PubMed: 33875558]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0000000000011997]
|
|
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|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chin, J. J., Behnam, B., Davids, M., Sharma, P., Zein, W. M., Wang, C., Chepa-Lotrea, X., Gallantine, W. B., Toro, C., Adams, D. R. Tifft, C. J., Gahl, W. A., Malicdan, M. C. V.
|
|
<strong>Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients.</strong>
|
|
Molec. Genet. Metab. 126: 188-195, 2019.
|
|
|
|
|
|
[PubMed: 30528883]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2018.12.001]
|
|
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|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gao, H., Boustany, R.-M. N., Espinola, J. A., Cotman, S. L., Srinidhi, L., Antonellis, K. A., Gillis, T., Qin, X., Liu, S., Donahue, L. R., Bronson, R. T., Faust, J. R., Stout, D., Haines, J. L., Lerner, T. J., MacDonald, M. E.
|
|
<strong>Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.</strong>
|
|
Am. J. Hum. Genet. 70: 324-335, 2002.
|
|
|
|
|
|
[PubMed: 11791207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/338190]
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kielar, C., Wishart, T. M., Palmer, A., Dihanich, S., Wong, A. M., Macauley, S. L., Chan, C.-H., Sands, M. S., Pearce, D. A., Cooper, J. D., Gillingwater, T. H.
|
|
<strong>Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease.</strong>
|
|
Hum. Molec. Genet. 18: 4066-4080, 2009.
|
|
|
|
|
|
[PubMed: 19640925]
|
|
|
|
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[Full Text: https://doi.org/10.1093/hmg/ddp355]
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Moore, S. J., Buckley, D. J., MacMillan, A., Marshall, H. D., Steele, L., Ray, P. N., Nawaz, Z., Baskin, B., Frecker, M., Carr, S. M., Ives, E., Parfrey, P. S.
|
|
<strong>The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland.</strong>
|
|
Clin. Genet. 74: 213-222, 2008.
|
|
|
|
|
|
[PubMed: 18684116]
|
|
|
|
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[Full Text: https://doi.org/10.1111/j.1399-0004.2008.01054.x]
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Sharp, J. D., Wheeler, R. B., Parker, K. A., Gardiner, R. M., Williams, R. E., Mole, S. E.
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<strong>Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis.</strong>
|
|
Hum. Mutat. 22: 35-42, 2003.
|
|
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|
|
[PubMed: 12815591]
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|
|
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[Full Text: https://doi.org/10.1002/humu.10227]
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Siintola, E., Topcu, M., Kohlschutter, A., Salonen, T., Joensuu, T., Anttonen, A.-K., Lehesjoki, A.-E.
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<strong>Two novel CLN6 mutations in variant late-infantile neuronal ceroid lipofuscinosis patients of Turkish origin.</strong>
|
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Clin. Genet. 68: 167-173, 2005.
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[PubMed: 15996215]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00471.x]
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Teixeira, C. A., Espinola, J., Huo, L., Kohlschutter, J., Persaud Sawin, D.-A., Minassian, B., Bessa, C. J. P., Guimaraes, A., Stephan, D. A., Sa Miranda, M. C., MacDonald, M. E., Gil Ribeiro, M., Boustany, R.-M. N.
|
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<strong>Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis.</strong>
|
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Hum. Mutat. 21: 502-508, 2003.
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[PubMed: 12673792]
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[Full Text: https://doi.org/10.1002/humu.10207]
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Wheeler, R. B., Sharp, J. D., Schultz, R. A., Joslin, J. M., Williams, R. E., Mole, S. E.
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<strong>The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein.</strong>
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Am. J. Hum. Genet. 70: 537-542, 2002.
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[PubMed: 11727201]
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[Full Text: https://doi.org/10.1086/338708]
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Bao Lige - updated : 07/03/2024<br>Cassandra L. Kniffin - updated : 12/01/2021<br>Cassandra L. Kniffin - updated : 12/01/2021<br>Hilary J. Vernon - updated : 07/22/2021<br>Sonja A. Rasmussen - updated : 02/19/2019<br>Cassandra L. Kniffin - updated : 5/16/2011<br>George E. Tiller - updated : 9/30/2010<br>Cassandra L. Kniffin - updated : 5/1/2009<br>Cassandra L. Kniffin - updated : 3/16/2006<br>Victor A. McKusick - updated : 8/18/2003<br>Victor A. McKusick - updated : 6/11/2003<br>Carol A. Bocchini - updated : 2/27/2002
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Victor A. McKusick : 2/27/2002
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