3429 lines
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Entry
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- *601515 - FIBROBLAST GROWTH FACTOR 14; FGF14
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*601515</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/601515">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<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=ENSG00000102466;t=ENST00000376143" 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=2259" 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=601515" 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=ENSG00000102466;t=ENST00000376143" 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_001321931,NM_001321932,NM_001321933,NM_001321934,NM_001321935,NM_001321936,NM_001321937,NM_001321938,NM_001321939,NM_001321940,NM_001321941,NM_001321942,NM_001321943,NM_001321944,NM_001321945,NM_001321946,NM_001321947,NM_001321948,NM_001321949,NM_001379342,NM_004115,NM_175929" 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_004115" 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=601515" 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=03305&isoform_id=03305_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/FGF14" 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/1563891,2494463,4758368,23238168,28200453,28872756,71681673,71682675,72533644,119629459,119629460,1013077126,1013077128,1013077130,1013077132,1013077134,1013077136,1013077138,1013077140,1013077142,1013077144,1013077146,1013077148,1013077150,1013077152,1013077154,1013077156,1013077158,1013077160,1013165743,1826689210" 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/Q92915" 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=2259" 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=ENSG00000102466;t=ENST00000376143" 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=FGF14" 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=FGF14" 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+2259" 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/FGF14" 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:2259" 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/2259" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr13&hgg_gene=ENST00000376143.5&hgg_start=101710804&hgg_end=102402443&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=601515[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=601515[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/FGF14/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/ENSG00000102466" 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=FGF14" 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=FGF14" 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=FGF14" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=FGF14&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/PA28110" 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:3671" 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:109189" 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/FGF14#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:109189" 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/2259/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/OMIA001723/" 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=2259" 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://wormbase.org/db/gene/gene?name=WBGene00002881;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060506-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
|
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</div>
|
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2259" 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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<div><a href="https://reactome.org/content/query?q=FGF14&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 719252002<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
|
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601515
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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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FIBROBLAST GROWTH FACTOR 14; FGF14
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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>
|
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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>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
FIBROBLAST GROWTH FACTOR HOMOLOGOUS FACTOR 4; FHF4
|
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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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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=FGF14" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FGF14</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/13/293?start=-3&limit=10&highlight=293">13q33.1</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr13:101710804-102402443&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">13:101,710,804-102,402,443</a> </span>
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</em>
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
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<tr class="active">
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<th>
|
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Location
|
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</th>
|
|
<th>
|
|
Phenotype
|
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|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=193003,620174" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/13/293?start=-3&limit=10&highlight=293">
|
|
13q33.1
|
|
</a>
|
|
</span>
|
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</td>
|
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Spinocerebellar ataxia 27A
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/193003"> 193003 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
|
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Spinocerebellar ataxia 27B, late-onset
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620174"> 620174 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
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</tbody>
|
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</table>
|
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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<p>The FGF14 gene encodes fibroblast growth factor-14, which is highly expressed in the brain, particularly in Purkinje cells where it interacts with voltage-gated channels to regulate neuronal excitability. FGF14 also plays a role in synaptic plasticity and neurogenesis in the hippocampus (summary by <a href="#6" class="mim-tip-reference" title="Piarroux, J., Riant, F., Humbertclaude, V., Remerand, G., Hadjadj, J., Rejou, F., Coubes, C., Pinson, L., Meyer, P., Roubertie, A. <strong>FGF14-related episodic ataxia: delineating the phenotype of episodic ataxia type 9.</strong> Ann. Clin. Transl. Neurol. 7: 565-572, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32162847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32162847</a>] [<a href="https://doi.org/10.1002/acn3.51005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32162847">Piarroux et al., 2020</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32162847" 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>FGF14 belongs to a subclass of fibroblast growth factors that are expressed in the developing and adult central nervous system (<a href="#8" class="mim-tip-reference" title="Smallwood, P. M., Munoz-Sanjuan, I., Tong, P., Macke, J. P., Hendry, S. H. C., Gilbert, D. J., Copeland, N. G., Jenkins, N. A., Nathans, J. <strong>Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development.</strong> Proc. Nat. Acad. Sci. 93: 9850-9857, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8790420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8790420</a>] [<a href="https://doi.org/10.1073/pnas.93.18.9850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8790420">Smallwood et al., 1996</a>). For a discussion on the FHF gene family, see FGF12 (FHF1; <a href="/entry/601513">601513</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8790420" 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="Smallwood, P. M., Munoz-Sanjuan, I., Tong, P., Macke, J. P., Hendry, S. H. C., Gilbert, D. J., Copeland, N. G., Jenkins, N. A., Nathans, J. <strong>Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development.</strong> Proc. Nat. Acad. Sci. 93: 9850-9857, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8790420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8790420</a>] [<a href="https://doi.org/10.1073/pnas.93.18.9850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8790420">Smallwood et al. (1996)</a> identified and characterized 4 novel members of the fibroblast growth factor (FGF) family, including FGF14, which they called FHF4. The genes were identified by a combination of random cDNA sequencing, database searches, and degenerate PCR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8790420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Wang, Q., McEwen, D. G., Ornitz, D. M. <strong>Subcellular and developmental expression of alternatively spliced forms of fibroblast growth factor 14.</strong> Mech. Dev. 90: 283-287, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10640713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10640713</a>] [<a href="https://doi.org/10.1016/s0925-4773(99)00241-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10640713">Wang et al. (2000)</a> characterized 2 mouse isoforms of Fgf14, which they called Fgf14-1a and Fgf14-1b, resulting from alternative first exons. In situ hybridization showed that Fgf14 is widely expressed in mouse brain, spinal cord, major arteries, and thymus between embryonic days 12.5 and 14.5. In mouse cerebellar development, Fgf14 was first observed at postnatal day 1 in postmitotic granule cells and later in migrating and postmigratory granule cells. The Fgf14 expression pattern in cerebellum was complementary to that of Math1 (ATOH1; <a href="/entry/601461">601461</a>), a marker for proliferating granule cells in the external germinal layer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10640713" 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 Southern blot hybridization of genomic DNA from rodent/human hybrid cell lines carrying individual human chromosomes, <a href="#8" class="mim-tip-reference" title="Smallwood, P. M., Munoz-Sanjuan, I., Tong, P., Macke, J. P., Hendry, S. H. C., Gilbert, D. J., Copeland, N. G., Jenkins, N. A., Nathans, J. <strong>Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development.</strong> Proc. Nat. Acad. Sci. 93: 9850-9857, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8790420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8790420</a>] [<a href="https://doi.org/10.1073/pnas.93.18.9850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8790420">Smallwood et al. (1996)</a> mapped the FGF14 gene to chromosome 13. Using an interspecific backcross mapping panel, they mapped the mouse homolog to chromosome 14, very close to the Rap2a (<a href="/entry/179540">179540</a>) gene, which in the human maps to 13q34. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8790420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Miura, S., Kosaka, K., Fujioka, R., Uchiyama, Y., Shimojo, T., Morikawa, T., Irie, A., Taniwaki, T., Shibata, H. <strong>Spinocerebellar ataxia 27 with a novel nonsense variant (lys177X) in FGF14.</strong> Europ. J. Med. Genet. 62: 172-176, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30017992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30017992</a>] [<a href="https://doi.org/10.1016/j.ejmg.2018.07.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30017992">Miura et al. (2019)</a> stated that the FGF14 gene maps to chromosome 13q33.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30017992" 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>Spinocerebellar Ataxia 27A</em></strong></p><p>
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In a large 3-generation Dutch family with spinocerebellar ataxia-27A (SCA27A; <a href="/entry/193003">193003</a>), <a href="#9" class="mim-tip-reference" title="van Swieten, J. C., Brusse, E., de Graaf, B. M., Krieger, E., van de Graaf, R., de Koning, I., Maat-Kievit, A., Leegwater, P., Dooijes, D., Oostra, B. A., Heutink, P. <strong>A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia.</strong> Am. J. Hum. Genet. 72: 191-199, 2003. Note: Erratum: Am. J. Hum. Genet. 72: 1078 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12489043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12489043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12489043[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/10.1086/345488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12489043">van Swieten et al. (2003)</a> identified a heterozygous missense mutation in the FGF14 gene (F145S; <a href="#0001">601515.0001</a>). The disorder was consistent with the occurrence of ataxia and paroxysmal dyskinesia in Fgf14 knockout mice (<a href="#10" class="mim-tip-reference" title="Wang, Q., Bardgett, M. E., Wong, M., Wozniak, D. F., Lou, J., McNeil, B. D., Chen, C., Nardi, A., Reid, D. C., Yamada, K., Ornitz, D. M. <strong>Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.</strong> Neuron 35: 25-38, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12123606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12123606</a>] [<a href="https://doi.org/10.1016/s0896-6273(02)00744-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12123606">Wang et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12489043+12123606" 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 1 of 208 unrelated patients with familial ataxia, <a href="#2" class="mim-tip-reference" title="Dalski, A., Atici, J., Kreuz, F. R., Hellenbroich, Y., Schwinger, E., Zuhlke, C. <strong>Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation and polymorphisms in patients with inherited ataxias.</strong> Europ. J. Hum. Genet. 13: 118-120, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15470364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15470364</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201286" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15470364">Dalski et al. (2005)</a> identified a heterozygous 1-bp deletion in the FGF14 gene (<a href="#0002">601515.0002</a>). The patient had early onset of the disorder and mildly impaired intellectual development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15470364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By whole-exome sequencing of genes known to cause SCA in a 62-year-old affected Japanese man, <a href="#4" class="mim-tip-reference" title="Miura, S., Kosaka, K., Fujioka, R., Uchiyama, Y., Shimojo, T., Morikawa, T., Irie, A., Taniwaki, T., Shibata, H. <strong>Spinocerebellar ataxia 27 with a novel nonsense variant (lys177X) in FGF14.</strong> Europ. J. Med. Genet. 62: 172-176, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30017992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30017992</a>] [<a href="https://doi.org/10.1016/j.ejmg.2018.07.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30017992">Miura et al. (2019)</a> identified a heterozygous nonsense mutation in the FGF14 gene (K177X; <a href="#0003">601515.0003</a>). The patient's father was reportedly affected, but neither detailed clinical information nor DNA was available for him. The variant was not found in public databases or in 502 Japanese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30017992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a mother and her 3 sons, of French Canadian origin, with variable manifestations of SCA27A, <a href="#1" class="mim-tip-reference" title="Choquet, K., La Piana, R., Brais, B. <strong>A novel frameshift mutation in FGF14 causes an autosomal dominant episodic ataxia.</strong> Neurogenetics 16: 233-236, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25566820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25566820</a>] [<a href="https://doi.org/10.1007/s10048-014-0436-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25566820">Choquet et al. (2015)</a> identified a heterozygous frameshift mutation in the FGF14 gene (<a href="#0004">601515.0004</a>). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not reported, but the authors postulated haploinsufficiency and suggested that SCA27 may be a type of channelopathy characterized by impaired function of voltage-gated ion channels due to mutation in the FGF14 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25566820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 7 affected members of a large multigenerational family (family A) with variable manifestations of SCA27A, <a href="#6" class="mim-tip-reference" title="Piarroux, J., Riant, F., Humbertclaude, V., Remerand, G., Hadjadj, J., Rejou, F., Coubes, C., Pinson, L., Meyer, P., Roubertie, A. <strong>FGF14-related episodic ataxia: delineating the phenotype of episodic ataxia type 9.</strong> Ann. Clin. Transl. Neurol. 7: 565-572, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32162847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32162847</a>] [<a href="https://doi.org/10.1002/acn3.51005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32162847">Piarroux et al. (2020)</a> identified a heterozygous nonsense mutation in the FGF14 gene (E147X; <a href="#0005">601515.0005</a>). An unrelated girl with SCA27A was found to carry a different mutation in the FGF14 gene (Y162X). The mutations, which were found by direct Sanger sequencing of a limited gene panel, segregated with the disorder in family A. Functional studies of the variants and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32162847" 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>Late-Onset Spinocerebellar Ataxia 27B</em></strong></p><p>
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In 128 patients, mostly of European or French Canadian descent, with late-onset spinocerebellar ataxia-27B (SCA27B; <a href="/entry/620174">620174</a>), <a href="#5" class="mim-tip-reference" title="Pellerin, D., Danzi, M. C., Wilke, C., Renaud, M., Fazal, S., Dicaire, M.-J., Scriba, C. K., Ashton, C., Yanick, C., Beijer, D., Rebelo, A., Rocca, C., and 40 others. <strong>Deep intronic FGF14 GAA repeat expansion in late-onset cerebellar ataxia.</strong> New Eng. J. Med. 388: 128-141, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36516086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36516086</a>] [<a href="https://doi.org/10.1056/NEJMoa2207406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36516086">Pellerin et al. (2023)</a> identified a heterozygous trinucleotide (GAA)n repeat expansion (equal to or greater than 250 repeats) in intron 1 of the FGF14 gene, which is included in pre-mRNA transcript 2 and not in pre-mRNA transcript 1 (<a href="#0006">601515.0006</a>). The GAA repeat was initially found in 21 affected individuals from 3 large multigenerational French Canadian families who underwent genome sequencing specifically looking for pathogenic repeat expansions. Subsequently, 4 independent cohorts of patients from different populations with unsolved late-onset cerebellar ataxia were screened for this FGF14 repeat expansion. GAA expansions equal to or greater than 250 repeats were found in 40 (61%) of 66 French Canadian patients, compared to 1% of controls; in 42 (18%) of 228 German patients, compared to 3% of controls; in 3 (15%) of 20 Australian patients, and in 3 (10%) of 31 East Asian Indian patients. The data suggested that 250 to 300 GAA expansions are likely to be pathogenic, although with incomplete penetrance, and that expansions greater than 300 are fully penetrant. Studies of patient cerebellar tissue and patient induced pluripotent stem cells (iPSCs) differentiated into motor neurons showed decreased FGF14 expression, suggesting haploinsufficiency as the pathogenetic mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36516086" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Rafehi, H., Read, J., Szmulewicz, D. J., Davies, K. C., Snell, P., Fearnley, L. G., Scott, L., Thomsen, M., Gillies, G., Pope, K., Bennett, M. F., Munro, J. E., and 19 others. <strong>An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14.</strong> Am. J. Hum. Genet. 110: 105-119, 2023. Note: Erratum: Am. J. Hum. Genet. 110: 1018 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36493768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36493768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36493768[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.2022.11.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36493768">Rafehi et al. (2023)</a> identified a GAA(n) repeat expansion in intron 1 of the FGF14 gene in patients with autosomal dominant adult-onset ataxia. Their results strongly supported a fully penetrant threshold of GAA(335) or greater and suggested that repeats between GAA(250) and GAA(335) is likely pathogenic, although with incomplete penetrance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36493768" 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>To study the role of Fgf14 in CNS development and adult brain function, <a href="#10" class="mim-tip-reference" title="Wang, Q., Bardgett, M. E., Wong, M., Wozniak, D. F., Lou, J., McNeil, B. D., Chen, C., Nardi, A., Reid, D. C., Yamada, K., Ornitz, D. M. <strong>Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.</strong> Neuron 35: 25-38, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12123606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12123606</a>] [<a href="https://doi.org/10.1016/s0896-6273(02)00744-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12123606">Wang et al. (2002)</a> generated Fgf14-deficient mice that expressed an FGF14/beta-galactosidase fusion protein in place of the normal Fgf14 protein. The Fgf14-deficient mice were viable, fertile, and anatomically normal, but developed ataxia and a paroxysmal hyperkinetic movement disorder. The authors noted that the motor abnormalities are associated with dysfunction of the basal ganglia system and resemble several human dystonia syndromes. Using neuropharmacologic studies, <a href="#10" class="mim-tip-reference" title="Wang, Q., Bardgett, M. E., Wong, M., Wozniak, D. F., Lou, J., McNeil, B. D., Chen, C., Nardi, A., Reid, D. C., Yamada, K., Ornitz, D. M. <strong>Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.</strong> Neuron 35: 25-38, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12123606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12123606</a>] [<a href="https://doi.org/10.1016/s0896-6273(02)00744-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12123606">Wang et al. (2002)</a> showed that the Fgf14-deficient mice had reduced responses to dopamine agonists. They suggested a function for Fgf14 in neuronal signaling, axonal trafficking, and synaptosomal function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12123606" 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 affected members of a 3-generation Dutch family with autosomal dominant spinocerebellar ataxia-27A (SCA27A; <a href="/entry/193003">193003</a>), <a href="#9" class="mim-tip-reference" title="van Swieten, J. C., Brusse, E., de Graaf, B. M., Krieger, E., van de Graaf, R., de Koning, I., Maat-Kievit, A., Leegwater, P., Dooijes, D., Oostra, B. A., Heutink, P. <strong>A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia.</strong> Am. J. Hum. Genet. 72: 191-199, 2003. Note: Erratum: Am. J. Hum. Genet. 72: 1078 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12489043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12489043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12489043[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/10.1086/345488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12489043">van Swieten et al. (2003)</a> identified a heterozygous phe145-to-ser (F145S) mutation in the FGF14 gene. As indicated by protein modeling, the amino acid change was predicted to reduce the stability of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12489043" 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="#3" class="mim-tip-reference" title="Laezza, F., Gerber, B. R., Lou, J. Y., Kozel, M. A., Hartman, H., Craig, A. M., Ornitz, D. M., Nerbonne, J. M. <strong>The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability.</strong> J. Neurosci. 27: 12033-12044, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17978045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17978045</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17978045[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/10.1523/JNEUROSCI.2282-07.2007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17978045">Laezza et al. (2007)</a> found that expression of human FGF14 with the F145S mutation in cultured rat hippocampal neurons markedly reduced localization of voltage-gated sodium channel alpha subunits to the axonal initial segment (AIS) compared with controls. Mutant FGF14 acted as a dominant negative and suppressed peak sodium channel current densities and excitability of hippocampal neurons. The authors proposed that FGF14 likely forms oligomers and that interaction between wildtype and mutant FGF14 in heterozygotes disrupts normal association between FGF14 and voltage-gated sodium channel alpha subunits at the AIS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17978045" 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 patient with spinocerebellar ataxia-27A (SCA27A; <a href="/entry/193003">193003</a>), <a href="#2" class="mim-tip-reference" title="Dalski, A., Atici, J., Kreuz, F. R., Hellenbroich, Y., Schwinger, E., Zuhlke, C. <strong>Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation and polymorphisms in patients with inherited ataxias.</strong> Europ. J. Hum. Genet. 13: 118-120, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15470364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15470364</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201286" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15470364">Dalski et al. (2005)</a> identified a heterozygous 1-bp deletion (487delA) in exon 4 of the FGF14 gene, resulting in premature termination of the protein and loss of one-third of amino acid residues. The mutation was not identified in 208 control samples. The patient had early onset of the disorder and mild mental retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15470364" 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">rs1555370787 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555370787;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=rs1555370787" 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=rs1555370787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>By whole-exome sequencing of genes known to cause spinocerebellar ataxia in a 62-year-old Japanese man with SCA (SCA27A; <a href="/entry/193003">193003</a>), <a href="#4" class="mim-tip-reference" title="Miura, S., Kosaka, K., Fujioka, R., Uchiyama, Y., Shimojo, T., Morikawa, T., Irie, A., Taniwaki, T., Shibata, H. <strong>Spinocerebellar ataxia 27 with a novel nonsense variant (lys177X) in FGF14.</strong> Europ. J. Med. Genet. 62: 172-176, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30017992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30017992</a>] [<a href="https://doi.org/10.1016/j.ejmg.2018.07.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30017992">Miura et al. (2019)</a> identified a heterozygous c.529A-T transversion (c.529A-T, NM_004115) in exon 4 of the FGF14 gene, predicting a lys177-to-ter (K177X) substitution with loss of the heparin-binding sites in the FGF domain. The authors suggested haploinsufficiency as the pathogenic mechanism. The variant was not found in public databases or in 502 Japanese controls. The patient's father was reportedly affected, but there was no detailed clinical information or DNA available for him. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30017992" 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 href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002291254" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002291254" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002291254</a>
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<p>In a mother and her 3 sons, of French Canadian origin, with variable manifestations of spinocerebellar ataxia-27A (SCA27A; <a href="/entry/193003">193003</a>), <a href="#1" class="mim-tip-reference" title="Choquet, K., La Piana, R., Brais, B. <strong>A novel frameshift mutation in FGF14 causes an autosomal dominant episodic ataxia.</strong> Neurogenetics 16: 233-236, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25566820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25566820</a>] [<a href="https://doi.org/10.1007/s10048-014-0436-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25566820">Choquet et al. (2015)</a> identified a heterozygous 1-bp insertion, c.211_212insA (chr3:102,527,628_102,527,629insT, hg19), in exon 2 of the FGF14 gene, resulting in a frameshift and premature termination (Ile71AsnfsTer27). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the dbSNP (build 138), 1000 Genomes Project, or Exome Variant Server databases or in 600 French Canadian controls. Functional studies of the variant and studies of patient cells were not reported, but the authors postulated haploinsufficiency and suggested that SCA27 may be a type of channelopathy characterized by impaired function of voltage-gated ion channels due to mutation in the FGF14 gene. The proband developed features of episodic ataxia in his late twenties that later progressed to permanent cerebellar ataxia with dysarthria and tremor. All 4 individuals had sustained nystagmus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25566820" 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">rs865878627 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs865878627;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=rs865878627" 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=rs865878627" 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=RCV002262429 OR RCV002291320" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002262429, RCV002291320" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002262429...</a>
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<p>In 7 affected members of a large multigenerational family (family A) with variable manifestations of spinocerebellar ataxia-27A (SCA27A; <a href="/entry/193003">193003</a>), <a href="#6" class="mim-tip-reference" title="Piarroux, J., Riant, F., Humbertclaude, V., Remerand, G., Hadjadj, J., Rejou, F., Coubes, C., Pinson, L., Meyer, P., Roubertie, A. <strong>FGF14-related episodic ataxia: delineating the phenotype of episodic ataxia type 9.</strong> Ann. Clin. Transl. Neurol. 7: 565-572, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32162847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32162847</a>] [<a href="https://doi.org/10.1002/acn3.51005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32162847">Piarroux et al. (2020)</a> identified a heterozygous c.439G-T transversion (c.439G-T, NM_004115.3) in the FGF14 gene, resulting in a glu147-to-ter (E147X) substitution. The mutation, which was found by direct Sanger sequencing of a limited gene panel, segregated with the disorder in the family. Other family members were reported as having hand tremor since childhood, but genetic testing was not performed. Functional studies of the variant and studies of patient cells were not performed. There was intrafamilial variability in age at onset and clinical manifestations: some had paroxysmal episodes consistent with episodic ataxia, whereas others had only postural tremor or nystagmus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32162847" 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 SPINOCEREBELLAR ATAXIA 27B, LATE-ONSET</strong>
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FGF14, (GAA)n REPEAT EXPANSION, IVS1
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV002472363" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002472363" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002472363</a>
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<p>In 128 patients, mostly of European of French Canadian descent, with late-onset spinocerebellar ataxia-27B (SCA27B; <a href="/entry/620174">620174</a>), <a href="#5" class="mim-tip-reference" title="Pellerin, D., Danzi, M. C., Wilke, C., Renaud, M., Fazal, S., Dicaire, M.-J., Scriba, C. K., Ashton, C., Yanick, C., Beijer, D., Rebelo, A., Rocca, C., and 40 others. <strong>Deep intronic FGF14 GAA repeat expansion in late-onset cerebellar ataxia.</strong> New Eng. J. Med. 388: 128-141, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36516086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36516086</a>] [<a href="https://doi.org/10.1056/NEJMoa2207406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36516086">Pellerin et al. (2023)</a> identified a heterozygous trinucleotide (GAA)n repeat expansion (equal to or greater than 250 repeats) in intron 1 of the FGF14 gene, which is included in pre-mRNA transcript 2 (NM_175929.3) and not in pre-mRNA transcript 1. The GAA repeat was initially found in 21 affected individuals from 3 large multigenerational French Canadian families who underwent genome sequencing specifically looking for pathogenic repeat expansions. The number of repeat units was greater than 300 in all but 1, who had 250 repeat units. One of the patients carried expansions on both alleles (300/716). The expansions, which were confirmed by Sanger sequencing, segregated with the disorder in the families in a pattern consistent with autosomal dominant inheritance. Eight (0.98%) of 816 control chromosomes carried an expansion of at least 250 triplet repeats, and none had a GAA expansion over 300 repeats. Subsequently, 4 independent cohorts of patients from different populations with unsolved late-onset cerebellar ataxia were screened for this FGF14 repeat expansion. GAA expansions equal to or greater than 250 repeats were found in 40 (61%) of 66 French Canadian patients, compared to 1% of controls; in 42 (18%) of 228 German patients, compared to 3% of controls; in 3 (15%) of 20 Australian patients, and in 3 (10%) of 31 East Asian Indian patients. The expansion was also present in affected relatives of some of the families. The repeat expansions were detected by long-range PCR, gel electrophoresis, and targeted long-range nanopore sequencing. Haplotype analysis of 5 French Canadian families was consistent with a founder effect in this population, but the authors noted that there were 2 Turkish and 3 Indian patients, suggesting that this repeat expansion may arise on multiple haplotype backgrounds. The findings also demonstrated that there is a high degree of polymorphism of this repeat locus in the general population. The data suggested that 250 to 300 GAA expansions are likely to be pathogenic, although with incomplete penetrance, and that expansions greater than 300 are fully penetrant. A study of 30 meiotic events showed that the transmission of expanded GAA alleles resulted in expansion in the female germline and contraction in the male germline. This was associated with an observed reduced paternal inheritance (30%). Postmortem cerebellar tissue derived from 2 patients and motor neurons derived from induced pluripotent stem cells (iPSCs) from 2 other patients showed decreased expression of total FGF14 and FGF14 transcript 2 and decreased levels of the protein, suggesting that the intronic GAA expansion interferes with FGF14 transcription. The findings were consistent with haploinsufficiency as the pathogenetic mechanism. The mean age at onset of episodic symptoms and progressive ataxia, respectively, was 55 and 59 years; none of the patients were under the age of 30. The authors postulated that this disorder may be a type of channelopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36516086" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Rafehi, H., Read, J., Szmulewicz, D. J., Davies, K. C., Snell, P., Fearnley, L. G., Scott, L., Thomsen, M., Gillies, G., Pope, K., Bennett, M. F., Munro, J. E., and 19 others. <strong>An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14.</strong> Am. J. Hum. Genet. 110: 105-119, 2023. Note: Erratum: Am. J. Hum. Genet. 110: 1018 only, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36493768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36493768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36493768[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.2022.11.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36493768">Rafehi et al. (2023)</a> identified a GAA(n) repeat expansion in intron 1 of the FGF14 gene in patients with autosomal dominant adult-onset ataxia. Among a cohort of 95 affected Australian individuals, 13 carried an allele greater than GAA(250), 4 of whom had more than 335 GAA repeats. Only 2 controls (0.6%) had a pure GAA expanded allele greater than GAA(250), with the maximum size being GAA(300). These data suggested that heterozygous expansion of a pure GAA repeat in FGF14 (over 250 repeats) represents a common cause of ataxia (OR = 24.3). A replication cohort of 104 German individuals with ataxia identified 9 (8.7%) patients with more than 335 GAA repeats and 6 (5.8%) with between 250 and 335 repeats, whereas 10 (5.3%) controls had more than 250 GAA repeats, but none had more than 335 GAA repeats. These data strongly supported a fully penetrant threshold of GAA(335) or greater and suggested that GAA(250) or greater is likely pathogenic, although with incomplete penetrance. The primary site of expression of the long isoform of FGF14 (1b) is in the brain. The GAA(n) repeat expansion is located within intron 1 of isoform 1b, suggesting that it may interfere with gene transcription. Functional studies of patient fibroblasts were inconclusive because FGF14 is not strongly expressed in those cells. The authors hypothesized that the pathogenic mechanism is reduced functional protein due to decreased expression of the allele with the expanded repeat. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36493768" 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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Choquet, K., La Piana, R., Brais, B.
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<strong>A novel frameshift mutation in FGF14 causes an autosomal dominant episodic ataxia.</strong>
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Neurogenetics 16: 233-236, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25566820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25566820</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25566820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10048-014-0436-7" target="_blank">Full Text</a>]
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Dalski, A., Atici, J., Kreuz, F. R., Hellenbroich, Y., Schwinger, E., Zuhlke, C.
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<strong>Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation and polymorphisms in patients with inherited ataxias.</strong>
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Europ. J. Hum. Genet. 13: 118-120, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15470364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15470364</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15470364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5201286" target="_blank">Full Text</a>]
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Laezza, F., Gerber, B. R., Lou, J. Y., Kozel, M. A., Hartman, H., Craig, A. M., Ornitz, D. M., Nerbonne, J. M.
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<strong>The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability.</strong>
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J. Neurosci. 27: 12033-12044, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17978045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17978045</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17978045[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=17978045" 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/10.1523/JNEUROSCI.2282-07.2007" target="_blank">Full Text</a>]
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Miura, S., Kosaka, K., Fujioka, R., Uchiyama, Y., Shimojo, T., Morikawa, T., Irie, A., Taniwaki, T., Shibata, H.
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<strong>Spinocerebellar ataxia 27 with a novel nonsense variant (lys177X) in FGF14.</strong>
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Europ. J. Med. Genet. 62: 172-176, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30017992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30017992</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30017992" 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.ejmg.2018.07.005" target="_blank">Full Text</a>]
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Pellerin, D., Danzi, M. C., Wilke, C., Renaud, M., Fazal, S., Dicaire, M.-J., Scriba, C. K., Ashton, C., Yanick, C., Beijer, D., Rebelo, A., Rocca, C., and 40 others.
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<strong>Deep intronic FGF14 GAA repeat expansion in late-onset cerebellar ataxia.</strong>
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New Eng. J. Med. 388: 128-141, 2023.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36516086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36516086</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36516086" 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/10.1056/NEJMoa2207406" 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="6" class="mim-anchor"></a>
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<a id="Piarroux2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Piarroux, J., Riant, F., Humbertclaude, V., Remerand, G., Hadjadj, J., Rejou, F., Coubes, C., Pinson, L., Meyer, P., Roubertie, A.
|
|
<strong>FGF14-related episodic ataxia: delineating the phenotype of episodic ataxia type 9.</strong>
|
|
Ann. Clin. Transl. Neurol. 7: 565-572, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32162847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32162847</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32162847" 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/acn3.51005" 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="7" class="mim-anchor"></a>
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<a id="Rafehi2023" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Rafehi, H., Read, J., Szmulewicz, D. J., Davies, K. C., Snell, P., Fearnley, L. G., Scott, L., Thomsen, M., Gillies, G., Pope, K., Bennett, M. F., Munro, J. E., and 19 others.
|
|
<strong>An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14.</strong>
|
|
Am. J. Hum. Genet. 110: 105-119, 2023. Note: Erratum: Am. J. Hum. Genet. 110: 1018 only, 2023.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36493768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36493768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36493768[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=36493768" 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.2022.11.015" 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="8" class="mim-anchor"></a>
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<a id="Smallwood1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Smallwood, P. M., Munoz-Sanjuan, I., Tong, P., Macke, J. P., Hendry, S. H. C., Gilbert, D. J., Copeland, N. G., Jenkins, N. A., Nathans, J.
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|
<strong>Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 9850-9857, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8790420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8790420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8790420" 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/10.1073/pnas.93.18.9850" 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="van Swieten2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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van Swieten, J. C., Brusse, E., de Graaf, B. M., Krieger, E., van de Graaf, R., de Koning, I., Maat-Kievit, A., Leegwater, P., Dooijes, D., Oostra, B. A., Heutink, P.
|
|
<strong>A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia.</strong>
|
|
Am. J. Hum. Genet. 72: 191-199, 2003. Note: Erratum: Am. J. Hum. Genet. 72: 1078 only, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12489043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12489043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12489043[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=12489043" 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/10.1086/345488" 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="Wang2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, Q., Bardgett, M. E., Wong, M., Wozniak, D. F., Lou, J., McNeil, B. D., Chen, C., Nardi, A., Reid, D. C., Yamada, K., Ornitz, D. M.
|
|
<strong>Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.</strong>
|
|
Neuron 35: 25-38, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12123606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12123606</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12123606" 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/s0896-6273(02)00744-4" 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="Wang2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, Q., McEwen, D. G., Ornitz, D. M.
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<strong>Subcellular and developmental expression of alternatively spliced forms of fibroblast growth factor 14.</strong>
|
|
Mech. Dev. 90: 283-287, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10640713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10640713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10640713" 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/s0925-4773(99)00241-5" 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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Alan F. Scott - updated : 04/27/2023
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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 : 01/18/2023<br>Cassandra L. Kniffin - updated : 12/21/2022<br>Cassandra L. Kniffin - updated : 10/11/2022<br>Sonja A. Rasmussen - updated : 09/23/2019<br>Cassandra L. Kniffin - updated : 4/11/2005<br>Victor A. McKusick - updated : 1/22/2003<br>Dawn Watkins-Chow - updated : 11/25/2002
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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 : 11/18/1996
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/01/2023
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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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mgross : 04/27/2023<br>alopez : 01/20/2023<br>ckniffin : 01/18/2023<br>alopez : 12/23/2022<br>ckniffin : 12/21/2022<br>alopez : 10/13/2022<br>ckniffin : 10/11/2022<br>ckniffin : 02/15/2021<br>carol : 09/24/2019<br>carol : 09/23/2019<br>carol : 09/16/2013<br>carol : 2/25/2013<br>wwang : 2/3/2010<br>wwang : 4/29/2005<br>wwang : 4/27/2005<br>ckniffin : 4/11/2005<br>carol : 7/2/2004<br>joanna : 3/17/2004<br>tkritzer : 1/31/2003<br>tkritzer : 1/24/2003<br>terry : 1/22/2003<br>carol : 1/21/2003<br>carol : 12/3/2002<br>tkritzer : 11/25/2002<br>tkritzer : 11/25/2002<br>carol : 4/6/1999<br>mark : 2/23/1997<br>mark : 11/18/1996
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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> 601515
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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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FIBROBLAST GROWTH FACTOR 14; FGF14
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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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FIBROBLAST GROWTH FACTOR HOMOLOGOUS FACTOR 4; FHF4
|
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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: FGF14</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 719252002;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: 13q33.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 13:101,710,804-102,402,443 </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>
|
|
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">
|
|
13q33.1
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
Spinocerebellar ataxia 27A
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
193003
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
Autosomal dominant
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
3
|
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</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Spinocerebellar ataxia 27B, late-onset
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
620174
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</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>
|
|
</h4>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>The FGF14 gene encodes fibroblast growth factor-14, which is highly expressed in the brain, particularly in Purkinje cells where it interacts with voltage-gated channels to regulate neuronal excitability. FGF14 also plays a role in synaptic plasticity and neurogenesis in the hippocampus (summary by Piarroux et al., 2020). </p><p>FGF14 belongs to a subclass of fibroblast growth factors that are expressed in the developing and adult central nervous system (Smallwood et al., 1996). For a discussion on the FHF gene family, see FGF12 (FHF1; 601513). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<span class="mim-text-font">
|
|
<p>Smallwood et al. (1996) identified and characterized 4 novel members of the fibroblast growth factor (FGF) family, including FGF14, which they called FHF4. The genes were identified by a combination of random cDNA sequencing, database searches, and degenerate PCR. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</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>Wang et al. (2000) characterized 2 mouse isoforms of Fgf14, which they called Fgf14-1a and Fgf14-1b, resulting from alternative first exons. In situ hybridization showed that Fgf14 is widely expressed in mouse brain, spinal cord, major arteries, and thymus between embryonic days 12.5 and 14.5. In mouse cerebellar development, Fgf14 was first observed at postnatal day 1 in postmitotic granule cells and later in migrating and postmigratory granule cells. The Fgf14 expression pattern in cerebellum was complementary to that of Math1 (ATOH1; 601461), a marker for proliferating granule cells in the external germinal layer. </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 Southern blot hybridization of genomic DNA from rodent/human hybrid cell lines carrying individual human chromosomes, Smallwood et al. (1996) mapped the FGF14 gene to chromosome 13. Using an interspecific backcross mapping panel, they mapped the mouse homolog to chromosome 14, very close to the Rap2a (179540) gene, which in the human maps to 13q34. </p><p>Miura et al. (2019) stated that the FGF14 gene maps to chromosome 13q33.1. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Spinocerebellar Ataxia 27A</em></strong></p><p>
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In a large 3-generation Dutch family with spinocerebellar ataxia-27A (SCA27A; 193003), van Swieten et al. (2003) identified a heterozygous missense mutation in the FGF14 gene (F145S; 601515.0001). The disorder was consistent with the occurrence of ataxia and paroxysmal dyskinesia in Fgf14 knockout mice (Wang et al., 2002). </p><p>In 1 of 208 unrelated patients with familial ataxia, Dalski et al. (2005) identified a heterozygous 1-bp deletion in the FGF14 gene (601515.0002). The patient had early onset of the disorder and mildly impaired intellectual development. </p><p>By whole-exome sequencing of genes known to cause SCA in a 62-year-old affected Japanese man, Miura et al. (2019) identified a heterozygous nonsense mutation in the FGF14 gene (K177X; 601515.0003). The patient's father was reportedly affected, but neither detailed clinical information nor DNA was available for him. The variant was not found in public databases or in 502 Japanese controls. </p><p>In a mother and her 3 sons, of French Canadian origin, with variable manifestations of SCA27A, Choquet et al. (2015) identified a heterozygous frameshift mutation in the FGF14 gene (601515.0004). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not reported, but the authors postulated haploinsufficiency and suggested that SCA27 may be a type of channelopathy characterized by impaired function of voltage-gated ion channels due to mutation in the FGF14 gene. </p><p>In 7 affected members of a large multigenerational family (family A) with variable manifestations of SCA27A, Piarroux et al. (2020) identified a heterozygous nonsense mutation in the FGF14 gene (E147X; 601515.0005). An unrelated girl with SCA27A was found to carry a different mutation in the FGF14 gene (Y162X). The mutations, which were found by direct Sanger sequencing of a limited gene panel, segregated with the disorder in family A. Functional studies of the variants and studies of patient cells were not performed. </p><p><strong><em>Late-Onset Spinocerebellar Ataxia 27B</em></strong></p><p>
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|
In 128 patients, mostly of European or French Canadian descent, with late-onset spinocerebellar ataxia-27B (SCA27B; 620174), Pellerin et al. (2023) identified a heterozygous trinucleotide (GAA)n repeat expansion (equal to or greater than 250 repeats) in intron 1 of the FGF14 gene, which is included in pre-mRNA transcript 2 and not in pre-mRNA transcript 1 (601515.0006). The GAA repeat was initially found in 21 affected individuals from 3 large multigenerational French Canadian families who underwent genome sequencing specifically looking for pathogenic repeat expansions. Subsequently, 4 independent cohorts of patients from different populations with unsolved late-onset cerebellar ataxia were screened for this FGF14 repeat expansion. GAA expansions equal to or greater than 250 repeats were found in 40 (61%) of 66 French Canadian patients, compared to 1% of controls; in 42 (18%) of 228 German patients, compared to 3% of controls; in 3 (15%) of 20 Australian patients, and in 3 (10%) of 31 East Asian Indian patients. The data suggested that 250 to 300 GAA expansions are likely to be pathogenic, although with incomplete penetrance, and that expansions greater than 300 are fully penetrant. Studies of patient cerebellar tissue and patient induced pluripotent stem cells (iPSCs) differentiated into motor neurons showed decreased FGF14 expression, suggesting haploinsufficiency as the pathogenetic mechanism. </p><p>Rafehi et al. (2023) identified a GAA(n) repeat expansion in intron 1 of the FGF14 gene in patients with autosomal dominant adult-onset ataxia. Their results strongly supported a fully penetrant threshold of GAA(335) or greater and suggested that repeats between GAA(250) and GAA(335) is likely pathogenic, although with incomplete penetrance. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>To study the role of Fgf14 in CNS development and adult brain function, Wang et al. (2002) generated Fgf14-deficient mice that expressed an FGF14/beta-galactosidase fusion protein in place of the normal Fgf14 protein. The Fgf14-deficient mice were viable, fertile, and anatomically normal, but developed ataxia and a paroxysmal hyperkinetic movement disorder. The authors noted that the motor abnormalities are associated with dysfunction of the basal ganglia system and resemble several human dystonia syndromes. Using neuropharmacologic studies, Wang et al. (2002) showed that the Fgf14-deficient mice had reduced responses to dopamine agonists. They suggested a function for Fgf14 in neuronal signaling, axonal trafficking, and synaptosomal function. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 SPINOCEREBELLAR ATAXIA 27A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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FGF14, PHE145SER
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<br />
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SNP: rs104894393,
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ClinVar: RCV002472354
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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 affected members of a 3-generation Dutch family with autosomal dominant spinocerebellar ataxia-27A (SCA27A; 193003), van Swieten et al. (2003) identified a heterozygous phe145-to-ser (F145S) mutation in the FGF14 gene. As indicated by protein modeling, the amino acid change was predicted to reduce the stability of the protein. </p><p>Laezza et al. (2007) found that expression of human FGF14 with the F145S mutation in cultured rat hippocampal neurons markedly reduced localization of voltage-gated sodium channel alpha subunits to the axonal initial segment (AIS) compared with controls. Mutant FGF14 acted as a dominant negative and suppressed peak sodium channel current densities and excitability of hippocampal neurons. The authors proposed that FGF14 likely forms oligomers and that interaction between wildtype and mutant FGF14 in heterozygotes disrupts normal association between FGF14 and voltage-gated sodium channel alpha subunits at the AIS. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0002 SPINOCEREBELLAR ATAXIA 27A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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FGF14, 1-BP DEL, 487A
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<br />
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SNP: rs587776685,
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ClinVar: RCV002472355
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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 with spinocerebellar ataxia-27A (SCA27A; 193003), Dalski et al. (2005) identified a heterozygous 1-bp deletion (487delA) in exon 4 of the FGF14 gene, resulting in premature termination of the protein and loss of one-third of amino acid residues. The mutation was not identified in 208 control samples. The patient had early onset of the disorder and mild mental retardation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0003 SPINOCEREBELLAR ATAXIA 27A</strong>
|
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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|
FGF14, LYS177TER
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<br />
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SNP: rs1555370787,
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|
ClinVar: RCV000580889, RCV002472357
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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>By whole-exome sequencing of genes known to cause spinocerebellar ataxia in a 62-year-old Japanese man with SCA (SCA27A; 193003), Miura et al. (2019) identified a heterozygous c.529A-T transversion (c.529A-T, NM_004115) in exon 4 of the FGF14 gene, predicting a lys177-to-ter (K177X) substitution with loss of the heparin-binding sites in the FGF domain. The authors suggested haploinsufficiency as the pathogenic mechanism. The variant was not found in public databases or in 502 Japanese controls. The patient's father was reportedly affected, but there was no detailed clinical information or DNA available for him. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0004 SPINOCEREBELLAR ATAXIA 27A</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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FGF14, 1-BP INS, 211A
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<br />
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ClinVar: RCV002291254
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a mother and her 3 sons, of French Canadian origin, with variable manifestations of spinocerebellar ataxia-27A (SCA27A; 193003), Choquet et al. (2015) identified a heterozygous 1-bp insertion, c.211_212insA (chr3:102,527,628_102,527,629insT, hg19), in exon 2 of the FGF14 gene, resulting in a frameshift and premature termination (Ile71AsnfsTer27). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the dbSNP (build 138), 1000 Genomes Project, or Exome Variant Server databases or in 600 French Canadian controls. Functional studies of the variant and studies of patient cells were not reported, but the authors postulated haploinsufficiency and suggested that SCA27 may be a type of channelopathy characterized by impaired function of voltage-gated ion channels due to mutation in the FGF14 gene. The proband developed features of episodic ataxia in his late twenties that later progressed to permanent cerebellar ataxia with dysarthria and tremor. All 4 individuals had sustained nystagmus. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0005 SPINOCEREBELLAR ATAXIA 27A</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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|
|
FGF14, GLU147TER
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<br />
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SNP: rs865878627,
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|
|
ClinVar: RCV002262429, RCV002291320
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|
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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 7 affected members of a large multigenerational family (family A) with variable manifestations of spinocerebellar ataxia-27A (SCA27A; 193003), Piarroux et al. (2020) identified a heterozygous c.439G-T transversion (c.439G-T, NM_004115.3) in the FGF14 gene, resulting in a glu147-to-ter (E147X) substitution. The mutation, which was found by direct Sanger sequencing of a limited gene panel, segregated with the disorder in the family. Other family members were reported as having hand tremor since childhood, but genetic testing was not performed. Functional studies of the variant and studies of patient cells were not performed. There was intrafamilial variability in age at onset and clinical manifestations: some had paroxysmal episodes consistent with episodic ataxia, whereas others had only postural tremor or nystagmus. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0006 SPINOCEREBELLAR ATAXIA 27B, LATE-ONSET</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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FGF14, (GAA)n REPEAT EXPANSION, IVS1
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<br />
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|
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ClinVar: RCV002472363
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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 128 patients, mostly of European of French Canadian descent, with late-onset spinocerebellar ataxia-27B (SCA27B; 620174), Pellerin et al. (2023) identified a heterozygous trinucleotide (GAA)n repeat expansion (equal to or greater than 250 repeats) in intron 1 of the FGF14 gene, which is included in pre-mRNA transcript 2 (NM_175929.3) and not in pre-mRNA transcript 1. The GAA repeat was initially found in 21 affected individuals from 3 large multigenerational French Canadian families who underwent genome sequencing specifically looking for pathogenic repeat expansions. The number of repeat units was greater than 300 in all but 1, who had 250 repeat units. One of the patients carried expansions on both alleles (300/716). The expansions, which were confirmed by Sanger sequencing, segregated with the disorder in the families in a pattern consistent with autosomal dominant inheritance. Eight (0.98%) of 816 control chromosomes carried an expansion of at least 250 triplet repeats, and none had a GAA expansion over 300 repeats. Subsequently, 4 independent cohorts of patients from different populations with unsolved late-onset cerebellar ataxia were screened for this FGF14 repeat expansion. GAA expansions equal to or greater than 250 repeats were found in 40 (61%) of 66 French Canadian patients, compared to 1% of controls; in 42 (18%) of 228 German patients, compared to 3% of controls; in 3 (15%) of 20 Australian patients, and in 3 (10%) of 31 East Asian Indian patients. The expansion was also present in affected relatives of some of the families. The repeat expansions were detected by long-range PCR, gel electrophoresis, and targeted long-range nanopore sequencing. Haplotype analysis of 5 French Canadian families was consistent with a founder effect in this population, but the authors noted that there were 2 Turkish and 3 Indian patients, suggesting that this repeat expansion may arise on multiple haplotype backgrounds. The findings also demonstrated that there is a high degree of polymorphism of this repeat locus in the general population. The data suggested that 250 to 300 GAA expansions are likely to be pathogenic, although with incomplete penetrance, and that expansions greater than 300 are fully penetrant. A study of 30 meiotic events showed that the transmission of expanded GAA alleles resulted in expansion in the female germline and contraction in the male germline. This was associated with an observed reduced paternal inheritance (30%). Postmortem cerebellar tissue derived from 2 patients and motor neurons derived from induced pluripotent stem cells (iPSCs) from 2 other patients showed decreased expression of total FGF14 and FGF14 transcript 2 and decreased levels of the protein, suggesting that the intronic GAA expansion interferes with FGF14 transcription. The findings were consistent with haploinsufficiency as the pathogenetic mechanism. The mean age at onset of episodic symptoms and progressive ataxia, respectively, was 55 and 59 years; none of the patients were under the age of 30. The authors postulated that this disorder may be a type of channelopathy. </p><p>Rafehi et al. (2023) identified a GAA(n) repeat expansion in intron 1 of the FGF14 gene in patients with autosomal dominant adult-onset ataxia. Among a cohort of 95 affected Australian individuals, 13 carried an allele greater than GAA(250), 4 of whom had more than 335 GAA repeats. Only 2 controls (0.6%) had a pure GAA expanded allele greater than GAA(250), with the maximum size being GAA(300). These data suggested that heterozygous expansion of a pure GAA repeat in FGF14 (over 250 repeats) represents a common cause of ataxia (OR = 24.3). A replication cohort of 104 German individuals with ataxia identified 9 (8.7%) patients with more than 335 GAA repeats and 6 (5.8%) with between 250 and 335 repeats, whereas 10 (5.3%) controls had more than 250 GAA repeats, but none had more than 335 GAA repeats. These data strongly supported a fully penetrant threshold of GAA(335) or greater and suggested that GAA(250) or greater is likely pathogenic, although with incomplete penetrance. The primary site of expression of the long isoform of FGF14 (1b) is in the brain. The GAA(n) repeat expansion is located within intron 1 of isoform 1b, suggesting that it may interfere with gene transcription. Functional studies of patient fibroblasts were inconclusive because FGF14 is not strongly expressed in those cells. The authors hypothesized that the pathogenic mechanism is reduced functional protein due to decreased expression of the allele with the expanded repeat. </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>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
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Choquet, K., La Piana, R., Brais, B.
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<strong>A novel frameshift mutation in FGF14 causes an autosomal dominant episodic ataxia.</strong>
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Neurogenetics 16: 233-236, 2015.
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[PubMed: 25566820]
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[Full Text: https://doi.org/10.1007/s10048-014-0436-7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Dalski, A., Atici, J., Kreuz, F. R., Hellenbroich, Y., Schwinger, E., Zuhlke, C.
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<strong>Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation and polymorphisms in patients with inherited ataxias.</strong>
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Europ. J. Hum. Genet. 13: 118-120, 2005.
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[PubMed: 15470364]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5201286]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Laezza, F., Gerber, B. R., Lou, J. Y., Kozel, M. A., Hartman, H., Craig, A. M., Ornitz, D. M., Nerbonne, J. M.
|
|
<strong>The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability.</strong>
|
|
J. Neurosci. 27: 12033-12044, 2007.
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[PubMed: 17978045]
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[Full Text: https://doi.org/10.1523/JNEUROSCI.2282-07.2007]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Miura, S., Kosaka, K., Fujioka, R., Uchiyama, Y., Shimojo, T., Morikawa, T., Irie, A., Taniwaki, T., Shibata, H.
|
|
<strong>Spinocerebellar ataxia 27 with a novel nonsense variant (lys177X) in FGF14.</strong>
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Pellerin, D., Danzi, M. C., Wilke, C., Renaud, M., Fazal, S., Dicaire, M.-J., Scriba, C. K., Ashton, C., Yanick, C., Beijer, D., Rebelo, A., Rocca, C., and 40 others.
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<strong>Deep intronic FGF14 GAA repeat expansion in late-onset cerebellar ataxia.</strong>
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Piarroux, J., Riant, F., Humbertclaude, V., Remerand, G., Hadjadj, J., Rejou, F., Coubes, C., Pinson, L., Meyer, P., Roubertie, A.
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<strong>FGF14-related episodic ataxia: delineating the phenotype of episodic ataxia type 9.</strong>
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Ann. Clin. Transl. Neurol. 7: 565-572, 2020.
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Rafehi, H., Read, J., Szmulewicz, D. J., Davies, K. C., Snell, P., Fearnley, L. G., Scott, L., Thomsen, M., Gillies, G., Pope, K., Bennett, M. F., Munro, J. E., and 19 others.
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<strong>An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14.</strong>
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Am. J. Hum. Genet. 110: 105-119, 2023. Note: Erratum: Am. J. Hum. Genet. 110: 1018 only, 2023.
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Smallwood, P. M., Munoz-Sanjuan, I., Tong, P., Macke, J. P., Hendry, S. H. C., Gilbert, D. J., Copeland, N. G., Jenkins, N. A., Nathans, J.
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van Swieten, J. C., Brusse, E., de Graaf, B. M., Krieger, E., van de Graaf, R., de Koning, I., Maat-Kievit, A., Leegwater, P., Dooijes, D., Oostra, B. A., Heutink, P.
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<strong>A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia.</strong>
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Wang, Q., Bardgett, M. E., Wong, M., Wozniak, D. F., Lou, J., McNeil, B. D., Chen, C., Nardi, A., Reid, D. C., Yamada, K., Ornitz, D. M.
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<strong>Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.</strong>
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Wang, Q., McEwen, D. G., Ornitz, D. M.
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<strong>Subcellular and developmental expression of alternatively spliced forms of fibroblast growth factor 14.</strong>
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[PubMed: 10640713]
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Alan F. Scott - updated : 04/27/2023<br>Cassandra L. Kniffin - updated : 01/18/2023<br>Cassandra L. Kniffin - updated : 12/21/2022<br>Cassandra L. Kniffin - updated : 10/11/2022<br>Sonja A. Rasmussen - updated : 09/23/2019<br>Cassandra L. Kniffin - updated : 4/11/2005<br>Victor A. McKusick - updated : 1/22/2003<br>Dawn Watkins-Chow - updated : 11/25/2002
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Victor A. McKusick : 11/18/1996
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