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Entry
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- *606157 - PANTOTHENATE KINASE 2; PANK2
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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">*606157</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="#geneStructure">Gene Structure</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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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606157">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 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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</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=ENSG00000125779;t=ENST00000610179" 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=80025" 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=606157" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<span class="panel-title">
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<span class="small">
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<a href="#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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<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=ENSG00000125779;t=ENST00000610179" 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_001324191,NM_001324192,NM_001324193,NM_001386393,NM_024960,NM_153638,NM_153640,NR_136715" 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_001386393" 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=606157" 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=05857&isoform_id=05857_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/PANK2" 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/10433049,19584334,20043243,21757676,23452046,24430167,24430175,40674650,62739678,85838513,118572682,119630878,119630880,119630881,119630883,133777202,133777305,187473264,1023300847,1023300911,1024249294,1894653491" 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/Q9BZ23" 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=80025" 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=ENSG00000125779;t=ENST00000610179" 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=PANK2" 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=PANK2" 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+80025" 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/PANK2" 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:80025" 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/80025" 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=chr20&hgg_gene=ENST00000610179.7&hgg_start=3888781&hgg_end=3929887&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 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://medlineplus.gov/genetics/gene/pank2" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=606157[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=606157[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://gnomad.broadinstitute.org/gene/ENSG00000125779" 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=PANK2" 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=PANK2" 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=PANK2" 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=PANK2&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/PA38048" 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:15894" 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://flybase.org/reports/FBgn0011205.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1921700" 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/PANK2#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:1921700" 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/80025/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://www.orthodb.org/?ncbi=80025" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-070112-1952" 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="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:606157" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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:80025" 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=PANK2&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> 2992000<br />
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<strong>ICD10CM:</strong> G23.0<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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606157
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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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PANTOTHENATE KINASE 2; PANK2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PANK2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PANK2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/20/64?start=-3&limit=10&highlight=64">20p13</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr20:3888781-3929887&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'})">20:3,888,781-3,929,887</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/20/64?start=-3&limit=10&highlight=64">
|
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20p13
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Neurodegeneration with brain iron accumulation 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/234200"> 234200 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/606157" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/606157" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
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</span>
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</h4>
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<p>Pantothenate kinase (<a href="https://enzyme.expasy.org/EC/2.7.2.33" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.2.33</a>) is an essential regulatory enzyme in CoA biosynthesis, catalyzing the cytosolic phosphorylation of pantothenate (vitamin B5), N-pantothenoylcysteine, and pantetheine. CoA is the major acyl carrier, playing a central role in intermediary and fatty acid metabolism. In both yeast and fly, each with only 1 pantothenate kinase gene, the null mutant is inviable (summary by <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" 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>Using linkage analysis of an extended Amish pedigree, <a href="#13" class="mim-tip-reference" title="Taylor, T. D., Litt, M., Kramer, P., Pandolfo, M., Angelini, L., Nardocci, N., Davis, S., Pineda, M., Hattori, H., Flett, P. J., Cilio, M. R., Bertini, E., Hayflick, S. J. <strong>Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13.</strong> Nature Genet. 14: 479-481, 1996. Note: Erratum: Nature Genet. 16: 109 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8944032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8944032</a>] [<a href="https://doi.org/10.1038/ng1296-479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8944032">Taylor et al. (1996)</a> defined an interval on 20p13 that contains the gene mutant in Hallervorden-Spatz disease, now known as neurodegeneration with brain iron accumulation-1 (NBIA1; <a href="/entry/234200">234200</a>). <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> narrowed the critical region for the disorder by genotyping polymorphic microsatellite markers in affected families. Analysis of candidate genes in this 1.4-Mb region led to the identification in the index family of a 7-bp deletion in the coding sequence of a gene with homology to murine pantothenate kinase-1. PANK2 is a member of a family of eukaryotic genes consisting of a group of 6 exons that encode homologous core proteins, preceded by a series of alternate initiating exons, some of which encode unique N-terminal peptides. By 5-prime RACE and EST analysis, <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> found evidence for at least 5 initiating exons for PANK2, but only 1 of these, exon 1C, has an open reading frame with potential initiation codons that splices in-frame to exon 2. <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> found a sequence similar to that of human PANK2 in mouse, with homology in the derived amino acid sequence extending to the leucine codon at nucleotide 31 but diverging 5-prime of it. There is precedence for the use of a leucine initiating codon in humans, which is probably read by a methionine tRNA. The leucine codon is flanked by a reasonable initiation consensus sequence. <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> also noted the presence of a stem-loop structure 14 nucleotides downstream from this leucine, the location of which has been shown to enhance translation initiation at nonconserved AUG and non-AUG initiation codons. The mouse stem-loop sequence is nearly identical, with only 3 nucleotide changes, 2 in the postulated loop of the stem loop and 1 that changes a GC to a GU basepair, which implies structural conservation. Because of this strong conservation, <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> proposed that the CUG may serve as an alternative initiation codon for translation in addition to one of the methionine codons downstream. There is also a 22-bp palindrome at the junction of spliced exons 1C and 2. This sequence may form a hairpin structure and thus explain why most PANK2 ESTs terminate just 3-prime of the palindrome. <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> speculated that this sequence may serve a regulatory function. PANK2 is ubiquitously expressed, including in retina and infant basal ganglia. <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> provided evidence for pantothenic kinase activity in PANK2 by showing that the human gene PANK2 can rescue the temperature-sensitive E. coli pantothenate kinase mutant. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8944032+11479594" 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="#6" class="mim-tip-reference" title="Hortnagel, K., Prokisch, H., Meitinger, T. <strong>An isoform of hPANK2, deficient in pantothenate kinase-associated neurodegeneration, localizes to mitochondria.</strong> Hum. Molec. Genet. 12: 321-327, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12554685/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12554685</a>] [<a href="https://doi.org/10.1093/hmg/ddg026" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12554685">Hortnagel et al. (2003)</a> determined the exon-intron structure of the human PANK2 gene and identified 2 alternatively used first exons. The resulting transcripts encode distinct isoforms of PANK2, one of which carries an N-terminal extension with a predicted mitochondrial targeting signal. An in vitro import assay and in vivo immunolocalization experiments demonstrated a mitochondrial localization of this isoform. The authors concluded that the symptoms observed in pantothenate kinase-associated neurodegeneration (<a href="/entry/234200">234200</a>) may be caused by a deficiency of the mitochondrial isoform; they further postulated the existence of a complete intramitochondrial pathway for de novo synthesis of coenzyme A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12554685" 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="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified 3 nonsense mutations in exon 1C of the PANK2 gene in affected individuals with classic Hallervorden-Spatz disease, also known as neurodegeneration with brain iron accumulation-1 (NBIA1; <a href="/entry/234200">234200</a>) or pantothenate kinase-associated neurodegeneration (PKAN), but not in controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" 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="Hayflick, S. J., Westaway, S. K., Levinson, B., Zhou, B., Johnson, M. A., Ching, K. H. L., Gitschier, J. <strong>Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.</strong> New Eng. J. Med. 348: 33-40, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12510040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12510040</a>] [<a href="https://doi.org/10.1056/NEJMoa020817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12510040">Hayflick et al. (2003)</a> performed clinical assessment and mutation screen of the PANK2 gene on 123 patients from 98 families with a diagnosis of Hallervorden-Spatz syndrome, classified on the basis of clinical assessment as having classic disease (characterized by early onset with rapid progression) or atypical disease (later onset with slow progression). PANK2 mutations were found in 66 of the 98 families. Of 49 families whose members had classic disease, all had mutations in PANK2. Of 49 families whose members had atypical disease, mutations were found in 17 (35%). Whereas almost all mutations in patients with atypical disease were missense, those in patients with classic disease resulted more often in predicted protein truncation. Patients with atypical disease who had PANK2 mutations were more likely to have prominent speech-related and psychiatric symptoms than patients with classic disease or mutation-negative patients with atypical disease. In all patients with pantothenate kinase-associated neurodegeneration, whether classic or atypical, T2-weighted MRI of the brain showed a specific pattern of hyperintensity within the hypointense medial globus pallidus. This pattern was not seen in any patients without mutations. Predicted levels of pantothenate kinase-2 protein correlated with the severity of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12510040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the 66 families with mutations in the PANK2 gene studied by <a href="#4" class="mim-tip-reference" title="Hayflick, S. J., Westaway, S. K., Levinson, B., Zhou, B., Johnson, M. A., Ching, K. H. L., Gitschier, J. <strong>Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.</strong> New Eng. J. Med. 348: 33-40, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12510040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12510040</a>] [<a href="https://doi.org/10.1056/NEJMoa020817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12510040">Hayflick et al. (2003)</a>, 2 PANK2 mutations, both of them missense mutations, accounted for one-third of the disease alleles, G411R (<a href="#0002">606157.0002</a>) and T418M (<a href="#0010">606157.0010</a>). G411R constituted 31 disease-related alleles in 27 families. Eighty-one percent of the 27 families with the G411R mutation were of European descent. In 6 families (4 with classic disease and 2 with atypical disease), the G411R mutation was found on one chromosome and no mutation was identified on the other. Families with only 1 identified mutation were not distinguishable from those with 2. Some of these mutations were undetectable with the screening method used, e.g., promoter mutations. Six of the 9 families with a single mutant allele had only the allele with the G411R mutation. This observation is striking because mutations in both alleles were detected in nearly all families, and it suggests that G411R may be semidominant, with 1 allele sufficient to cause disease given certain genetic backgrounds. Against this hypothesis was the fact that no disease phenotype was observed in G411R-heterozygous carrier parents of affected persons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12510040" 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 16 patients with PKAN, <a href="#10" class="mim-tip-reference" title="Pellecchia, M. T., Valente, E. M., Cif, L., Salvi, S., Albanese, A., Scarano, V., Bonuccelli, U., Bentivoglio, A. R., D'Amico, A., Marelli, C., Di Giorgio, A., Coubes, P., Barone, P., Dallapiccola, B. <strong>The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration.</strong> Neurology 64: 1810-1812, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15911822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15911822</a>] [<a href="https://doi.org/10.1212/01.WNL.0000161843.52641.EC" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15911822">Pellecchia et al. (2005)</a> identified 12 mutations in the PANK2 gene, including 5 novel mutations. They found no genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15911822" 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="Hartig, M. B., Hortnagel, K., Garavaglia, B., Zorzi, G., Kmiec, T., Klopstock, T., Rostasy, K., Svetel, M., Kostic, V. S., Schuelke, M., Botz, E., Weindl, A., Novakovic, I., Nardocci, N., Prokisch, H., Meitinger, T. <strong>Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation.</strong> Ann. Neurol. 59: 248-256, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16437574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16437574</a>] [<a href="https://doi.org/10.1002/ana.20771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16437574">Hartig et al. (2006)</a> identified homozygous or compound heterozygous PANK2 mutations in 48 of 72 patients with PKAN. Deletions accounted for 4% of mutated alleles. There was a correlation between predicted loss-of-function alleles and earlier age at disease onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16437574" 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 patient with NBIA1, who was originally reported as having 'HARP syndrome' by <a href="#5" class="mim-tip-reference" title="Higgins, J. J., Patterson, M. C., Papadopoulos, N. M., Brady, R. O., Pentchev, P. G., Barton, N. W. <strong>Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome).</strong> Neurology 42: 194-198, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1734303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1734303</a>] [<a href="https://doi.org/10.1212/wnl.42.1.194" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1734303">Higgins et al. (1992)</a>, <a href="#1" class="mim-tip-reference" title="Ching, K. H. L., Westaway, S. K., Gitschier, J., Higgins, J. J., Hayflick, S. J. <strong>HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration.</strong> Neurology 58: 1673-1674, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12058097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12058097</a>] [<a href="https://doi.org/10.1212/wnl.58.11.1673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12058097">Ching et al. (2002)</a> identified a homozygous nonsense mutation in the PANK2 gene (R371X; <a href="#0011">606157.0011</a>). The patient had classic features of PKAN, but also had a specific lipoprotein abnormality. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1734303+12058097" 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 20 patients from the Dominican Republic with NBIA1, <a href="#2" class="mim-tip-reference" title="Delgado, R. F., Sanchez, P. R., Speckter, H., Then, E. P., Jimenez, R., Oviedo, J., Dellani, P. R., Foerster, B., Stoeter, P. <strong>Missense PANK2 mutation without 'eye of the tiger' sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN).</strong> J Magn. Reson. Imaging 35: 788-794, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22127788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22127788</a>] [<a href="https://doi.org/10.1002/jmri.22884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22127788">Delgado et al. (2012)</a> identified a homozygous missense mutation in the PANK2 gene (Y227C; <a href="#0016">606157.0016</a>). One homozygous carrier was asymptomatic at 7 years of age ('preclinical' case). Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22127788" 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="Kuo, Y.-M., Duncan, J. L., Westaway, S. K., Yang, H., Nune, G., Xu, E. Y., Hayflick, S. J., Gitschier, J. <strong>Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia.</strong> Hum. Molec. Genet. 14: 49-57, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15525657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15525657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15525657[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddi005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15525657">Kuo et al. (2005)</a> generated a mouse knockout of the murine Pank2 gene. Homozygous null mice gradually developed retinal degeneration with progressive photoreceptor decline, significantly lower scotopic a- and b-wave amplitudes, decreased cell number and disruption of the outer segment, and reduced pupillary constriction response. Homozygous male mutants were infertile due to azoospermia, a condition that was not appreciated in affected humans with pantothenate kinase-associated neurodegeneration (<a href="/entry/234200">234200</a>). In contrast to the human, homozygous null mice exhibited no basal ganglia changes or dystonia. By immunohistochemistry, Pank2 was localized to mitochondria in both retina and spermatozoa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15525657" 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>Drosophila has only 1 PANK gene, fumble (fbl), which encodes several isoforms of pantothenate kinase, including a long isoform fblL that localizes to mitochondria and shorter isoforms fblS1 and fblS2 that localize to the cytosol. <a href="#14" class="mim-tip-reference" title="Wu, Z., Li, C., Lv, S., Zhou, B. <strong>Pantothenate kinase-associated neurodegeneration: insights from a Drosophila model.</strong> Hum. Molec. Genet. 18: 3659-3672, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19602483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19602483</a>] [<a href="https://doi.org/10.1093/hmg/ddp314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19602483">Wu et al. (2009)</a> introduced various isoforms of Drosophila fbl and human PANK2 into flies to study their in vivo functions. Only mitochondria-targeted FblL or human PANK2 was able to rescue a hypomorphic fbl(1) mutation, with the rescuing ability dependent on the expression level of the transgene. Transgenic lines with low expression of normal fbl or PANK2 displayed similar phenotypes as PANK2-mutant transgenic flies. These PANK2 mutants all showed reduced enzyme activity, and phenotype severity correlated with in vitro enzyme activity. Cytosolic PANK3 (<a href="/entry/606161">606161</a>) and PANK4 (<a href="/entry/606162">606162</a>) could partially rescue all fbl defects except male sterility. The authors concluded that fbl is the ortholog of human PANK2, and PANK2 is functionally more potent than PANK3 and PANK4 in vivo. <a href="#14" class="mim-tip-reference" title="Wu, Z., Li, C., Lv, S., Zhou, B. <strong>Pantothenate kinase-associated neurodegeneration: insights from a Drosophila model.</strong> Hum. Molec. Genet. 18: 3659-3672, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19602483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19602483</a>] [<a href="https://doi.org/10.1093/hmg/ddp314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19602483">Wu et al. (2009)</a> suggested that mitochondria-located pantothenate kinase is required to achieve the maximal enzymatic activity to fulfill the most challenging biologic tasks such as maintaining male fertility and optimal neuronal function, and PKAN features are mainly due to the reduction of the total cellular pantothenate kinase activity in the most susceptible regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19602483" 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 an individual with classic pantothenate kinase-associated neurodegeneration (<a href="/entry/234200">234200</a>), <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified a homozygous 7-bp deletion in exon 2 of the PANK2 gene, resulting in a frameshift. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" 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 10 individuals with classic pantothenate kinase-associated neurodegeneration (<a href="/entry/234200">234200</a>), <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified a homozygous 1261G-A transition in exon 6 of the PANK2 gene, resulting in a glycine-to-arginine substitution at codon 411 (G411R). The mutation was also seen in 7 individuals with atypical PKAN. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" 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 an individual with classic pantothenate kinase-associated neurodegeneration (<a href="/entry/234200">234200</a>), <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified a C-to-G transversion at nucleotide 270 in exon 1C of the PANK2 gene, resulting in a tyrosine-to-termination substitution at codon 80 (Y80X). This mutation was found in compound heterozygosity with arg154 to tyr (<a href="#0004">606157.0004</a>). In another affected individual, the mutation was found in homozygosity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
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PANK2, ARG154TRP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852961 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852961;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852961?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852961" 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=rs137852961" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004810 OR RCV002460885" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004810, RCV002460885" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004810...</a>
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<p>In an individual with classic pantothenate kinase-associated neurodegeneration (<a href="/entry/234200">234200</a>), <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> found a C-to-T transition at nucleotide 490 of the PANK2 gene, resulting in an arg-to-trp substitution at codon 154 (R154W). This patient was compound heterozygous for the Y80X mutation (<a href="#0003">606157.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0005 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
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</h4>
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PANK2, ARG176CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852962 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852962;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852962?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852962" 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=rs137852962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004811" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004811" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004811</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>In an individual with classic pantothenate kinase-associated neurodegeneration (<a href="/entry/234200">234200</a>), <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified a C-to-T transition at nucleotide 556 of the PANK2 gene, resulting in an arg-to-cys substitution at codon 176 (R176C). This individual was a compound heterozygote for the G411R mutation (<a href="#0002">606157.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</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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PANK2, SER361ASN
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852963 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852963;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=rs137852963" 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=rs137852963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004812" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004812" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004812</a>
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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 an individual with classic pantothenate kinase-associated neurodegeneration (<a href="/entry/234200">234200</a>) who was compound heterozygous for an R145W mutation (<a href="#0004">606157.0004</a>) in the PANK2 gene, <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified a G-to-A transition on the other allele, resulting in a ser361-to-asn (S361N) amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</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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<div style="float: left;">
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PANK2, SER240PRO
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852964 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852964;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=rs137852964" 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=rs137852964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003985014" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003985014" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003985014</a>
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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 an individual with atypical pantothenate kinase-associated neurodegeneration (NBIA1; <a href="/entry/234200">234200</a>), <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified a homozygous mutation, a T-to-C transition at nucleotide 751 of the PANK2 gene, resulting in a serine-to-proline substitution at codon 240 (S240P). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0008 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</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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<div style="float: left;">
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PANK2, THR124ALA
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852965 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852965;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852965?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852965" 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=rs137852965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001851655 OR RCV003234892" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001851655, RCV003234892" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001851655...</a>
|
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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 an individual with atypical pantothenate kinase-associated neurodegeneration (NBIA1; <a href="/entry/234200">234200</a>), <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified an A-to-G transition at nucleotide 400 of the PANK2 gene, resulting in a threonine-to-alanine substitution at codon 124 (T124A). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0009 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</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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<div style="float: left;">
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PANK2, ARG168CYS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852966 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852966;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852966?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852966" 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=rs137852966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001753400 OR RCV003985015" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001753400, RCV003985015" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001753400...</a>
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<p>In an individual with atypical pantothenate kinase-associated neurodegeneration (NBIA1; <a href="/entry/234200">234200</a>), <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified a C-to-T transition at nucleotide 532of the PANK2 gene, resulting in an arg-to-cys substitution at codon 168 (R168C). This patient was compound heterozygous for the G411R mutation (<a href="#0002">606157.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852967 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852967;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852967?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852967" 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=rs137852967" 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=RCV000004816 OR RCV000132733 OR RCV001310448 OR RCV002512773 OR RCV004755710" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004816, RCV000132733, RCV001310448, RCV002512773, RCV004755710" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004816...</a>
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<p>In individuals with both typical and atypical pantothenate kinase-associated neurodegeneration (NBIA1; <a href="/entry/234200">234200</a>), <a href="#15" class="mim-tip-reference" title="Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J. <strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong> Nature Genet. 28: 345-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>] [<a href="https://doi.org/10.1038/ng572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479594">Zhou et al. (2001)</a> identified a C-to-T transition at nucleotide 1283 of the PANK2 gene, resulting in a threonine-to-methionine substitution at codon 418 (T418M). This mutation was found in homozygosity in 2 patients with classical PKAN, and in compound heterozygosity with the G411R mutation (<a href="#0002">606157.0002</a>) in an individual with atypical PKAN. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" 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="Hayflick, S. J., Westaway, S. K., Levinson, B., Zhou, B., Johnson, M. A., Ching, K. H. L., Gitschier, J. <strong>Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.</strong> New Eng. J. Med. 348: 33-40, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12510040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12510040</a>] [<a href="https://doi.org/10.1056/NEJMoa020817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12510040">Hayflick et al. (2003)</a> found the T418M mutation on 10 alleles in 6 of 66 families with PANK2 mutations causing Hallervorden-Spatz syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12510040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0011 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
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PANK2, ARG371TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852968 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852968;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852968?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852968" 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=rs137852968" 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=RCV000821698 OR RCV001003628" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000821698, RCV001003628" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000821698...</a>
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<p>In a patient with neurodegeneration with brain iron accumulation-1 (NBIA1; <a href="/entry/234200">234200</a>), <a href="#1" class="mim-tip-reference" title="Ching, K. H. L., Westaway, S. K., Gitschier, J., Higgins, J. J., Hayflick, S. J. <strong>HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration.</strong> Neurology 58: 1673-1674, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12058097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12058097</a>] [<a href="https://doi.org/10.1212/wnl.58.11.1673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12058097">Ching et al. (2002)</a> demonstrated homozygosity for a C-to-T transition at nucleotide 1111 in exon 5 of the PANK2 gene. The mutation changed an arginine codon to a stop codon at amino acid 371 and shortened PANK2 by 89 amino acids. <a href="#1" class="mim-tip-reference" title="Ching, K. H. L., Westaway, S. K., Gitschier, J., Higgins, J. J., Hayflick, S. J. <strong>HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration.</strong> Neurology 58: 1673-1674, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12058097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12058097</a>] [<a href="https://doi.org/10.1212/wnl.58.11.1673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12058097">Ching et al. (2002)</a> suspected that the patient was the offspring of consanguineous parents because they came from a village of 500 inhabitants. The patient demonstrated severe spasticity and dystonia from early childhood. At age 10, she was shown to have pigmentary retinopathy on funduscopic examination and the 'eye of the tiger' sign on brain MRI. Peripheral blood smear and electron microscopy demonstrated marked acanthocytosis that was not due to an intrinsic erythrocyte protein defect. On high-resolution lipoprotein electrophoresis, she demonstrated absence of the pre-beta fraction and normal blood levels of cholesterol, triglycerides, high and low density lipoprotein cholesterol, and apolipoproteins A, B, and E. The patient was originally reported by <a href="#5" class="mim-tip-reference" title="Higgins, J. J., Patterson, M. C., Papadopoulos, N. M., Brady, R. O., Pentchev, P. G., Barton, N. W. <strong>Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome).</strong> Neurology 42: 194-198, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1734303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1734303</a>] [<a href="https://doi.org/10.1212/wnl.42.1.194" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1734303">Higgins et al. (1992)</a> as having 'HARP syndrome' due to a lipoprotein abnormality. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1734303+12058097" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28939088 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939088;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=rs28939088" 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=rs28939088" 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=RCV003984799" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003984799" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003984799</a>
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<p>In a patient with neurodegeneration with brain iron accumulation-1 (NBIA1; <a href="/entry/234200">234200</a>), <a href="#7" class="mim-tip-reference" title="Houlden, H., Lincoln, S., Farrer, M., Cleland, P. G., Hardy, J., Orrell, R. W. <strong>Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz syndromes are allelic.</strong> Neurology 61: 1423-1426, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14638969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14638969</a>] [<a href="https://doi.org/10.1212/01.wnl.0000094120.09977.92" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14638969">Houlden et al. (2003)</a> identified compound heterozygosity for mutations in the PANK2 gene: a 980T-C change in exon 4, resulting in a met327-to-thr (M327T) substitution, and a splice site mutation (<a href="#0013">606157.0013</a>). Her unaffected father and 2 of his unaffected brothers were heterozygous for the M327T mutation. The patient's mother and sister, both of whom had acanthocytosis and hypoprebetalipoproteinemia without neurologic abnormalities, were heterozygous for the splice site mutation. The proband was initially reported by <a href="#9" class="mim-tip-reference" title="Orrell, R. W., Amrolia, P. J., Heald, A., Cleland, P. G., Owen, J. S., Morgan-Hughes, J. A., Harding, A. E., Marsden, C. D. <strong>Acanthocytosis, retinitis pigmentosa, and pallidal degeneration: a report of three patients, including the second reported case with hypoprebetalipoproteinemia (HARP syndrome).</strong> Neurology 45: 487-492, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7898702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7898702</a>] [<a href="https://doi.org/10.1212/wnl.45.3.487" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7898702">Orrell et al. (1995)</a> as having 'HARP syndrome' due to a lipoprotein abnormality. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7898702+14638969" 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>.0013 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs148987163 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs148987163;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs148987163?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs148987163" 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=rs148987163" 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=RCV000004821 OR RCV002247248 OR RCV002512774" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004821, RCV002247248, RCV002512774" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004821...</a>
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<p>For discussion of the G-to-T transversion at the splice site of exon 5 (IVS4-1G-T) in the PANK2 gene that was found in compound heterozygous state in a patient with neurodegeneration with brain iron accumulation-1 (NBIA1; <a href="/entry/234200">234200</a>) by <a href="#7" class="mim-tip-reference" title="Houlden, H., Lincoln, S., Farrer, M., Cleland, P. G., Hardy, J., Orrell, R. W. <strong>Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz syndromes are allelic.</strong> Neurology 61: 1423-1426, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14638969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14638969</a>] [<a href="https://doi.org/10.1212/01.wnl.0000094120.09977.92" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14638969">Houlden et al. (2003)</a>, see <a href="#0012">606157.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14638969" 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="Hayflick, S. J., Westaway, S. K., Levinson, B., Zhou, B., Johnson, M. A., Ching, K. H. L., Gitschier, J. <strong>Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.</strong> New Eng. J. Med. 348: 33-40, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12510040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12510040</a>] [<a href="https://doi.org/10.1056/NEJMoa020817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12510040">Hayflick et al. (2003)</a> identified the IVS4-1G-T mutation in 2 patients with NBIA1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12510040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs766251466 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs766251466;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs766251466?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs766251466" 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=rs766251466" 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=RCV000004822 OR RCV001574642" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004822, RCV001574642" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004822...</a>
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<p>In affected members from 4 Dutch families with pantothenate kinase-associated neurodegeneration (NBIA1; <a href="/entry/234200">234200</a>), <a href="#11" class="mim-tip-reference" title="Rump, P., Lemmink, H. H., Verschuuren-Bemelmans, C. C., Grootscholten, P. M., Fock, J. M., Hayflick, S. J., Westaway, S. K., Vos, Y. J., van Essen, A. J. <strong>A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect.</strong> Neurogenetics 6: 201-207, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16240131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16240131</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16240131[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/10.1007/s10048-005-0018-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16240131">Rump et al. (2005)</a> identified a 3-bp deletion (1142delGAG) in the PANK2 gene. The in-frame deletion is predicted to result in substitution of arg371 and glu372 with a glutamine in the catalytic domain of the protein. Five patients from 3 families were homozygous for the mutation. The patient from the fourth family was compound heterozygous for the deletion and a second mutation (S68X; <a href="#0015">606157.0015</a>). Haplotype analysis suggested a founder effect that arose in Friesland, a northern province of the Netherlands, at the beginning of the ninth century, approximately 38 generations ago. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16240131" 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=RCV000004823" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004823" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004823</a>
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<p>In a Dutch patient with pantothenate kinase-associated neurodegeneration (NBIA1; <a href="/entry/234200">234200</a>), <a href="#11" class="mim-tip-reference" title="Rump, P., Lemmink, H. H., Verschuuren-Bemelmans, C. C., Grootscholten, P. M., Fock, J. M., Hayflick, S. J., Westaway, S. K., Vos, Y. J., van Essen, A. J. <strong>A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect.</strong> Neurogenetics 6: 201-207, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16240131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16240131</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16240131[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/10.1007/s10048-005-0018-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16240131">Rump et al. (2005)</a> identified compound heterozygosity for 2 mutations in the PANK2 gene: a 3-bp deletion (<a href="#0014">606157.0014</a>) and a 233C-A transversion, resulting in a ser68-to-ter (S68X) substitution. The patient had a severe form of the disorder and died at age 12 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16240131" 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">rs1555787646 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555787646;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=rs1555787646" 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=rs1555787646" 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=RCV000544004 OR RCV002466529" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000544004, RCV002466529" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000544004...</a>
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<p>In 20 patients from the Dominican Republic with neurodegeneration with brain iron accumulation-1 (NBIA1; <a href="/entry/234200">234200</a>), <a href="#2" class="mim-tip-reference" title="Delgado, R. F., Sanchez, P. R., Speckter, H., Then, E. P., Jimenez, R., Oviedo, J., Dellani, P. R., Foerster, B., Stoeter, P. <strong>Missense PANK2 mutation without 'eye of the tiger' sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN).</strong> J Magn. Reson. Imaging 35: 788-794, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22127788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22127788</a>] [<a href="https://doi.org/10.1002/jmri.22884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22127788">Delgado et al. (2012)</a> identified a homozygous c.680A-G transition in the PANK2 gene, resulting in a tyr227-to-cys (Y227C) substitution. One homozygous carrier was asymptomatic at 7 years of age ('preclinical' case). Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22127788" 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="#12" class="mim-tip-reference" title="Schiessl-Weyer, J., Roa, P., Laccone, F., Kluge, B., Tichy, A., De Almeida Ribeiro, E., Prohaska, R., Stoeter, P., Siegl, C., Salzer, U. <strong>Acanthocytosis and the c.680 A-G mutation in the PANK2 gene: a study enrolling a cohort of PKAN patients from the Dominican Republic.</strong> PLoS One 10: e0125861, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25915509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25915509</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25915509[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/10.1371/journal.pone.0125861" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25915509">Schiessl-Weyer et al. (2015)</a> examined erythrocyte morphology in 25 patients from the Dominican Republic with PKAN and a homozygous Y227C mutation (c.680A-G, NM_153638.2) in exon 2 of the PANK2 gene, most of whom were previously reported by <a href="#2" class="mim-tip-reference" title="Delgado, R. F., Sanchez, P. R., Speckter, H., Then, E. P., Jimenez, R., Oviedo, J., Dellani, P. R., Foerster, B., Stoeter, P. <strong>Missense PANK2 mutation without 'eye of the tiger' sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN).</strong> J Magn. Reson. Imaging 35: 788-794, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22127788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22127788</a>] [<a href="https://doi.org/10.1002/jmri.22884" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22127788">Delgado et al. (2012)</a>. <a href="#12" class="mim-tip-reference" title="Schiessl-Weyer, J., Roa, P., Laccone, F., Kluge, B., Tichy, A., De Almeida Ribeiro, E., Prohaska, R., Stoeter, P., Siegl, C., Salzer, U. <strong>Acanthocytosis and the c.680 A-G mutation in the PANK2 gene: a study enrolling a cohort of PKAN patients from the Dominican Republic.</strong> PLoS One 10: e0125861, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25915509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25915509</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25915509[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/10.1371/journal.pone.0125861" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25915509">Schiessl-Weyer et al. (2015)</a> noted that PANK2 and other enzymes of the coenzyme A biosynthetic pathway are normal constituents of the erythrocyte cytosol; they hypothesized that reduced CoA levels could result in aberrant lipid-based signaling processes and dysfunctional organization of protein complexes at the erythrocyte plasma membrane. The somewhat later onset of disease in these patients (average 10.8 years), absence of pigmentary retinopathy, and mild or no intellectual decline suggested that the mutant protein likely has some residual enzymatic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22127788+25915509" 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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Neurology 58: 1673-1674, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12058097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12058097</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12058097" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Missense PANK2 mutation without 'eye of the tiger' sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN).</strong>
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J Magn. Reson. Imaging 35: 788-794, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22127788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22127788</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22127788" 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/jmri.22884" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.20771" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJMoa020817" target="_blank">Full Text</a>]
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<a id="Higgins1992" class="mim-anchor"></a>
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<strong>Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome).</strong>
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[<a href="https://doi.org/10.1212/wnl.42.1.194" target="_blank">Full Text</a>]
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<a id="Hortnagel2003" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1093/hmg/ddg026" target="_blank">Full Text</a>]
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<strong>Compound heterozygous PANK2 mutations confirm HARP and Hallervorden-Spatz syndromes are allelic.</strong>
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Neurology 61: 1423-1426, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14638969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14638969</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14638969" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000094120.09977.92" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15525657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15525657</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15525657[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=15525657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi005" target="_blank">Full Text</a>]
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Orrell, R. W., Amrolia, P. J., Heald, A., Cleland, P. G., Owen, J. S., Morgan-Hughes, J. A., Harding, A. E., Marsden, C. D.
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<strong>Acanthocytosis, retinitis pigmentosa, and pallidal degeneration: a report of three patients, including the second reported case with hypoprebetalipoproteinemia (HARP syndrome).</strong>
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Neurology 45: 487-492, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7898702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7898702</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7898702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.45.3.487" target="_blank">Full Text</a>]
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Pellecchia, M. T., Valente, E. M., Cif, L., Salvi, S., Albanese, A., Scarano, V., Bonuccelli, U., Bentivoglio, A. R., D'Amico, A., Marelli, C., Di Giorgio, A., Coubes, P., Barone, P., Dallapiccola, B.
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<strong>The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration.</strong>
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Neurology 64: 1810-1812, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15911822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15911822</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15911822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.WNL.0000161843.52641.EC" target="_blank">Full Text</a>]
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<a id="Rump2005" class="mim-anchor"></a>
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Rump, P., Lemmink, H. H., Verschuuren-Bemelmans, C. C., Grootscholten, P. M., Fock, J. M., Hayflick, S. J., Westaway, S. K., Vos, Y. J., van Essen, A. J.
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<strong>A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect.</strong>
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Neurogenetics 6: 201-207, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16240131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16240131</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16240131[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=16240131" 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/s10048-005-0018-9" target="_blank">Full Text</a>]
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<a id="Schiessl-Weyer2015" class="mim-anchor"></a>
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Schiessl-Weyer, J., Roa, P., Laccone, F., Kluge, B., Tichy, A., De Almeida Ribeiro, E., Prohaska, R., Stoeter, P., Siegl, C., Salzer, U.
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<strong>Acanthocytosis and the c.680 A-G mutation in the PANK2 gene: a study enrolling a cohort of PKAN patients from the Dominican Republic.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25915509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25915509</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25915509[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=25915509" 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/10.1371/journal.pone.0125861" target="_blank">Full Text</a>]
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Taylor, T. D., Litt, M., Kramer, P., Pandolfo, M., Angelini, L., Nardocci, N., Davis, S., Pineda, M., Hattori, H., Flett, P. J., Cilio, M. R., Bertini, E., Hayflick, S. J.
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<strong>Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8944032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8944032</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8944032" 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/ng1296-479" target="_blank">Full Text</a>]
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Wu, Z., Li, C., Lv, S., Zhou, B.
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<strong>Pantothenate kinase-associated neurodegeneration: insights from a Drosophila model.</strong>
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Hum. Molec. Genet. 18: 3659-3672, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19602483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19602483</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19602483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp314" target="_blank">Full Text</a>]
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<a id="Zhou2001" class="mim-anchor"></a>
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Zhou, B., Westaway, S. K., Levinson, B., Johnson, M. A., Gitschier, J., Hayflick, S. J.
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<strong>A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.</strong>
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Nature Genet. 28: 345-349, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479594" 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/ng572" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 03/05/2024
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George E. Tiller - updated : 7/8/2010<br>George E. Tiller - updated : 10/31/2007<br>Cassandra L. Kniffin - updated : 4/11/2006<br>Cassandra L. Kniffin - updated : 3/2/2006<br>Cassandra L. Kniffin - updated : 8/16/2005<br>George E. Tiller - updated : 1/3/2005<br>Cassandra L. Kniffin - updated : 2/3/2004<br>Victor A. McKusick - updated : 1/24/2003<br>Victor A. McKusick - updated : 9/3/2002
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Ada Hamosh : 7/30/2001
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<span class="mim-text-font">
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carol : 03/14/2024
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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carol : 03/13/2024<br>ckniffin : 03/05/2024<br>carol : 07/19/2017<br>carol : 04/16/2013<br>terry : 5/25/2012<br>wwang : 7/22/2010<br>terry : 7/8/2010<br>carol : 3/8/2010<br>carol : 3/1/2010<br>carol : 2/25/2010<br>alopez : 11/2/2007<br>terry : 10/31/2007<br>wwang : 4/19/2006<br>ckniffin : 4/11/2006<br>wwang : 3/14/2006<br>ckniffin : 3/2/2006<br>wwang : 8/23/2005<br>ckniffin : 8/16/2005<br>alopez : 1/3/2005<br>tkritzer : 2/6/2004<br>ckniffin : 2/3/2004<br>cwells : 11/18/2003<br>terry : 1/24/2003<br>alopez : 11/1/2002<br>carol : 9/18/2002<br>tkritzer : 9/17/2002<br>tkritzer : 9/17/2002<br>terry : 9/3/2002<br>alopez : 7/30/2001
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<div class="container visible-print-block">
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606157
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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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PANTOTHENATE KINASE 2; PANK2
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: PANK2</em></strong>
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</span>
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</p>
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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> 2992000;
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<strong>ICD10CM:</strong> G23.0;
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</span>
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</p>
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<br />
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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: 20p13
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Genomic coordinates <span class="small">(GRCh38)</span> : 20:3,888,781-3,929,887 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</tr>
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</thead>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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20p13
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</span>
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</td>
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<td>
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<span class="mim-font">
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Neurodegeneration with brain iron accumulation 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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234200
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Pantothenate kinase (EC 2.7.2.33) is an essential regulatory enzyme in CoA biosynthesis, catalyzing the cytosolic phosphorylation of pantothenate (vitamin B5), N-pantothenoylcysteine, and pantetheine. CoA is the major acyl carrier, playing a central role in intermediary and fatty acid metabolism. In both yeast and fly, each with only 1 pantothenate kinase gene, the null mutant is inviable (summary by Zhou et al., 2001). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using linkage analysis of an extended Amish pedigree, Taylor et al. (1996) defined an interval on 20p13 that contains the gene mutant in Hallervorden-Spatz disease, now known as neurodegeneration with brain iron accumulation-1 (NBIA1; 234200). Zhou et al. (2001) narrowed the critical region for the disorder by genotyping polymorphic microsatellite markers in affected families. Analysis of candidate genes in this 1.4-Mb region led to the identification in the index family of a 7-bp deletion in the coding sequence of a gene with homology to murine pantothenate kinase-1. PANK2 is a member of a family of eukaryotic genes consisting of a group of 6 exons that encode homologous core proteins, preceded by a series of alternate initiating exons, some of which encode unique N-terminal peptides. By 5-prime RACE and EST analysis, Zhou et al. (2001) found evidence for at least 5 initiating exons for PANK2, but only 1 of these, exon 1C, has an open reading frame with potential initiation codons that splices in-frame to exon 2. Zhou et al. (2001) found a sequence similar to that of human PANK2 in mouse, with homology in the derived amino acid sequence extending to the leucine codon at nucleotide 31 but diverging 5-prime of it. There is precedence for the use of a leucine initiating codon in humans, which is probably read by a methionine tRNA. The leucine codon is flanked by a reasonable initiation consensus sequence. Zhou et al. (2001) also noted the presence of a stem-loop structure 14 nucleotides downstream from this leucine, the location of which has been shown to enhance translation initiation at nonconserved AUG and non-AUG initiation codons. The mouse stem-loop sequence is nearly identical, with only 3 nucleotide changes, 2 in the postulated loop of the stem loop and 1 that changes a GC to a GU basepair, which implies structural conservation. Because of this strong conservation, Zhou et al. (2001) proposed that the CUG may serve as an alternative initiation codon for translation in addition to one of the methionine codons downstream. There is also a 22-bp palindrome at the junction of spliced exons 1C and 2. This sequence may form a hairpin structure and thus explain why most PANK2 ESTs terminate just 3-prime of the palindrome. Zhou et al. (2001) speculated that this sequence may serve a regulatory function. PANK2 is ubiquitously expressed, including in retina and infant basal ganglia. Zhou et al. (2001) provided evidence for pantothenic kinase activity in PANK2 by showing that the human gene PANK2 can rescue the temperature-sensitive E. coli pantothenate kinase mutant. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hortnagel et al. (2003) determined the exon-intron structure of the human PANK2 gene and identified 2 alternatively used first exons. The resulting transcripts encode distinct isoforms of PANK2, one of which carries an N-terminal extension with a predicted mitochondrial targeting signal. An in vitro import assay and in vivo immunolocalization experiments demonstrated a mitochondrial localization of this isoform. The authors concluded that the symptoms observed in pantothenate kinase-associated neurodegeneration (234200) may be caused by a deficiency of the mitochondrial isoform; they further postulated the existence of a complete intramitochondrial pathway for de novo synthesis of coenzyme A. </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>Zhou et al. (2001) identified 3 nonsense mutations in exon 1C of the PANK2 gene in affected individuals with classic Hallervorden-Spatz disease, also known as neurodegeneration with brain iron accumulation-1 (NBIA1; 234200) or pantothenate kinase-associated neurodegeneration (PKAN), but not in controls. </p><p>Hayflick et al. (2003) performed clinical assessment and mutation screen of the PANK2 gene on 123 patients from 98 families with a diagnosis of Hallervorden-Spatz syndrome, classified on the basis of clinical assessment as having classic disease (characterized by early onset with rapid progression) or atypical disease (later onset with slow progression). PANK2 mutations were found in 66 of the 98 families. Of 49 families whose members had classic disease, all had mutations in PANK2. Of 49 families whose members had atypical disease, mutations were found in 17 (35%). Whereas almost all mutations in patients with atypical disease were missense, those in patients with classic disease resulted more often in predicted protein truncation. Patients with atypical disease who had PANK2 mutations were more likely to have prominent speech-related and psychiatric symptoms than patients with classic disease or mutation-negative patients with atypical disease. In all patients with pantothenate kinase-associated neurodegeneration, whether classic or atypical, T2-weighted MRI of the brain showed a specific pattern of hyperintensity within the hypointense medial globus pallidus. This pattern was not seen in any patients without mutations. Predicted levels of pantothenate kinase-2 protein correlated with the severity of the disease. </p><p>In the 66 families with mutations in the PANK2 gene studied by Hayflick et al. (2003), 2 PANK2 mutations, both of them missense mutations, accounted for one-third of the disease alleles, G411R (606157.0002) and T418M (606157.0010). G411R constituted 31 disease-related alleles in 27 families. Eighty-one percent of the 27 families with the G411R mutation were of European descent. In 6 families (4 with classic disease and 2 with atypical disease), the G411R mutation was found on one chromosome and no mutation was identified on the other. Families with only 1 identified mutation were not distinguishable from those with 2. Some of these mutations were undetectable with the screening method used, e.g., promoter mutations. Six of the 9 families with a single mutant allele had only the allele with the G411R mutation. This observation is striking because mutations in both alleles were detected in nearly all families, and it suggests that G411R may be semidominant, with 1 allele sufficient to cause disease given certain genetic backgrounds. Against this hypothesis was the fact that no disease phenotype was observed in G411R-heterozygous carrier parents of affected persons. </p><p>In 16 patients with PKAN, Pellecchia et al. (2005) identified 12 mutations in the PANK2 gene, including 5 novel mutations. They found no genotype/phenotype correlations. </p><p>Hartig et al. (2006) identified homozygous or compound heterozygous PANK2 mutations in 48 of 72 patients with PKAN. Deletions accounted for 4% of mutated alleles. There was a correlation between predicted loss-of-function alleles and earlier age at disease onset. </p><p>In a patient with NBIA1, who was originally reported as having 'HARP syndrome' by Higgins et al. (1992), Ching et al. (2002) identified a homozygous nonsense mutation in the PANK2 gene (R371X; 606157.0011). The patient had classic features of PKAN, but also had a specific lipoprotein abnormality. </p><p>In 20 patients from the Dominican Republic with NBIA1, Delgado et al. (2012) identified a homozygous missense mutation in the PANK2 gene (Y227C; 606157.0016). One homozygous carrier was asymptomatic at 7 years of age ('preclinical' case). Functional studies of the variant were not performed. </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>Kuo et al. (2005) generated a mouse knockout of the murine Pank2 gene. Homozygous null mice gradually developed retinal degeneration with progressive photoreceptor decline, significantly lower scotopic a- and b-wave amplitudes, decreased cell number and disruption of the outer segment, and reduced pupillary constriction response. Homozygous male mutants were infertile due to azoospermia, a condition that was not appreciated in affected humans with pantothenate kinase-associated neurodegeneration (234200). In contrast to the human, homozygous null mice exhibited no basal ganglia changes or dystonia. By immunohistochemistry, Pank2 was localized to mitochondria in both retina and spermatozoa. </p><p>Drosophila has only 1 PANK gene, fumble (fbl), which encodes several isoforms of pantothenate kinase, including a long isoform fblL that localizes to mitochondria and shorter isoforms fblS1 and fblS2 that localize to the cytosol. Wu et al. (2009) introduced various isoforms of Drosophila fbl and human PANK2 into flies to study their in vivo functions. Only mitochondria-targeted FblL or human PANK2 was able to rescue a hypomorphic fbl(1) mutation, with the rescuing ability dependent on the expression level of the transgene. Transgenic lines with low expression of normal fbl or PANK2 displayed similar phenotypes as PANK2-mutant transgenic flies. These PANK2 mutants all showed reduced enzyme activity, and phenotype severity correlated with in vitro enzyme activity. Cytosolic PANK3 (606161) and PANK4 (606162) could partially rescue all fbl defects except male sterility. The authors concluded that fbl is the ortholog of human PANK2, and PANK2 is functionally more potent than PANK3 and PANK4 in vivo. Wu et al. (2009) suggested that mitochondria-located pantothenate kinase is required to achieve the maximal enzymatic activity to fulfill the most challenging biologic tasks such as maintaining male fertility and optimal neuronal function, and PKAN features are mainly due to the reduction of the total cellular pantothenate kinase activity in the most susceptible regions. </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>ALLELIC VARIANTS</strong>
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</span>
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<strong>16 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 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</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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PANK2, 7-BP DEL, NT627
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<br />
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SNP: rs879253712,
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ClinVar: RCV000004806
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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 an individual with classic pantothenate kinase-associated neurodegeneration (234200), Zhou et al. (2001) identified a homozygous 7-bp deletion in exon 2 of the PANK2 gene, resulting in a frameshift. </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 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</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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PANK2, GLY411ARG
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<br />
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SNP: rs137852959,
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gnomAD: rs137852959,
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ClinVar: RCV000004807, RCV000132732, RCV000190815, RCV000224470, RCV001588799, RCV002496261, RCV004766980
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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 10 individuals with classic pantothenate kinase-associated neurodegeneration (234200), Zhou et al. (2001) identified a homozygous 1261G-A transition in exon 6 of the PANK2 gene, resulting in a glycine-to-arginine substitution at codon 411 (G411R). The mutation was also seen in 7 individuals with atypical PKAN. </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 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</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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PANK2, TYR80TER
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<br />
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SNP: rs137852960,
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gnomAD: rs137852960,
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ClinVar: RCV000004809
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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 an individual with classic pantothenate kinase-associated neurodegeneration (234200), Zhou et al. (2001) identified a C-to-G transversion at nucleotide 270 in exon 1C of the PANK2 gene, resulting in a tyrosine-to-termination substitution at codon 80 (Y80X). This mutation was found in compound heterozygosity with arg154 to tyr (606157.0004). In another affected individual, the mutation was found in homozygosity. </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>.0004 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</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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PANK2, ARG154TRP
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<br />
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SNP: rs137852961,
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gnomAD: rs137852961,
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ClinVar: RCV000004810, RCV002460885
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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 an individual with classic pantothenate kinase-associated neurodegeneration (234200), Zhou et al. (2001) found a C-to-T transition at nucleotide 490 of the PANK2 gene, resulting in an arg-to-trp substitution at codon 154 (R154W). This patient was compound heterozygous for the Y80X mutation (606157.0003). </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 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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PANK2, ARG176CYS
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<br />
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SNP: rs137852962,
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gnomAD: rs137852962,
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ClinVar: RCV000004811
|
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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 an individual with classic pantothenate kinase-associated neurodegeneration (234200), Zhou et al. (2001) identified a C-to-T transition at nucleotide 556 of the PANK2 gene, resulting in an arg-to-cys substitution at codon 176 (R176C). This individual was a compound heterozygote for the G411R mutation (606157.0002). </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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PANK2, SER361ASN
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<br />
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SNP: rs137852963,
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ClinVar: RCV000004812
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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 an individual with classic pantothenate kinase-associated neurodegeneration (234200) who was compound heterozygous for an R145W mutation (606157.0004) in the PANK2 gene, Zhou et al. (2001) identified a G-to-A transition on the other allele, resulting in a ser361-to-asn (S361N) amino acid substitution. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
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PANK2, SER240PRO
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<br />
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SNP: rs137852964,
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|
ClinVar: RCV003985014
|
|
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|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual with atypical pantothenate kinase-associated neurodegeneration (NBIA1; 234200), Zhou et al. (2001) identified a homozygous mutation, a T-to-C transition at nucleotide 751 of the PANK2 gene, resulting in a serine-to-proline substitution at codon 240 (S240P). </p>
|
|
</span>
|
|
</div>
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|
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|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
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|
<div>
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PANK2, THR124ALA
|
|
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|
|
<br />
|
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|
|
SNP: rs137852965,
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|
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|
|
gnomAD: rs137852965,
|
|
|
|
|
|
ClinVar: RCV001851655, RCV003234892
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual with atypical pantothenate kinase-associated neurodegeneration (NBIA1; 234200), Zhou et al. (2001) identified an A-to-G transition at nucleotide 400 of the PANK2 gene, resulting in a threonine-to-alanine substitution at codon 124 (T124A). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PANK2, ARG168CYS
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs137852966,
|
|
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|
|
gnomAD: rs137852966,
|
|
|
|
|
|
ClinVar: RCV001753400, RCV003985015
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual with atypical pantothenate kinase-associated neurodegeneration (NBIA1; 234200), Zhou et al. (2001) identified a C-to-T transition at nucleotide 532of the PANK2 gene, resulting in an arg-to-cys substitution at codon 168 (R168C). This patient was compound heterozygous for the G411R mutation (606157.0002). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PANK2, THR418MET
|
|
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|
|
|
<br />
|
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|
|
SNP: rs137852967,
|
|
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|
|
|
gnomAD: rs137852967,
|
|
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|
|
|
ClinVar: RCV000004816, RCV000132733, RCV001310448, RCV002512773, RCV004755710
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In individuals with both typical and atypical pantothenate kinase-associated neurodegeneration (NBIA1; 234200), Zhou et al. (2001) identified a C-to-T transition at nucleotide 1283 of the PANK2 gene, resulting in a threonine-to-methionine substitution at codon 418 (T418M). This mutation was found in homozygosity in 2 patients with classical PKAN, and in compound heterozygosity with the G411R mutation (606157.0002) in an individual with atypical PKAN. </p><p>Hayflick et al. (2003) found the T418M mutation on 10 alleles in 6 of 66 families with PANK2 mutations causing Hallervorden-Spatz syndrome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PANK2, ARG371TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852968,
|
|
|
|
|
|
gnomAD: rs137852968,
|
|
|
|
|
|
ClinVar: RCV000821698, RCV001003628
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with neurodegeneration with brain iron accumulation-1 (NBIA1; 234200), Ching et al. (2002) demonstrated homozygosity for a C-to-T transition at nucleotide 1111 in exon 5 of the PANK2 gene. The mutation changed an arginine codon to a stop codon at amino acid 371 and shortened PANK2 by 89 amino acids. Ching et al. (2002) suspected that the patient was the offspring of consanguineous parents because they came from a village of 500 inhabitants. The patient demonstrated severe spasticity and dystonia from early childhood. At age 10, she was shown to have pigmentary retinopathy on funduscopic examination and the 'eye of the tiger' sign on brain MRI. Peripheral blood smear and electron microscopy demonstrated marked acanthocytosis that was not due to an intrinsic erythrocyte protein defect. On high-resolution lipoprotein electrophoresis, she demonstrated absence of the pre-beta fraction and normal blood levels of cholesterol, triglycerides, high and low density lipoprotein cholesterol, and apolipoproteins A, B, and E. The patient was originally reported by Higgins et al. (1992) as having 'HARP syndrome' due to a lipoprotein abnormality. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PANK2, MET327THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28939088,
|
|
|
|
|
|
|
|
ClinVar: RCV003984799
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with neurodegeneration with brain iron accumulation-1 (NBIA1; 234200), Houlden et al. (2003) identified compound heterozygosity for mutations in the PANK2 gene: a 980T-C change in exon 4, resulting in a met327-to-thr (M327T) substitution, and a splice site mutation (606157.0013). Her unaffected father and 2 of his unaffected brothers were heterozygous for the M327T mutation. The patient's mother and sister, both of whom had acanthocytosis and hypoprebetalipoproteinemia without neurologic abnormalities, were heterozygous for the splice site mutation. The proband was initially reported by Orrell et al. (1995) as having 'HARP syndrome' due to a lipoprotein abnormality. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PANK2, IVS4AS, G-T, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs148987163,
|
|
|
|
|
|
gnomAD: rs148987163,
|
|
|
|
|
|
ClinVar: RCV000004821, RCV002247248, RCV002512774
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the G-to-T transversion at the splice site of exon 5 (IVS4-1G-T) in the PANK2 gene that was found in compound heterozygous state in a patient with neurodegeneration with brain iron accumulation-1 (NBIA1; 234200) by Houlden et al. (2003), see 606157.0012. </p><p>Hayflick et al. (2003) identified the IVS4-1G-T mutation in 2 patients with NBIA1. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PANK2, 3-BP DEL, 1142GAG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs766251466,
|
|
|
|
|
|
gnomAD: rs766251466,
|
|
|
|
|
|
ClinVar: RCV000004822, RCV001574642
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members from 4 Dutch families with pantothenate kinase-associated neurodegeneration (NBIA1; 234200), Rump et al. (2005) identified a 3-bp deletion (1142delGAG) in the PANK2 gene. The in-frame deletion is predicted to result in substitution of arg371 and glu372 with a glutamine in the catalytic domain of the protein. Five patients from 3 families were homozygous for the mutation. The patient from the fourth family was compound heterozygous for the deletion and a second mutation (S68X; 606157.0015). Haplotype analysis suggested a founder effect that arose in Friesland, a northern province of the Netherlands, at the beginning of the ninth century, approximately 38 generations ago. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PANK2, SER68TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852969,
|
|
|
|
|
|
gnomAD: rs137852969,
|
|
|
|
|
|
ClinVar: RCV000004823
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Dutch patient with pantothenate kinase-associated neurodegeneration (NBIA1; 234200), Rump et al. (2005) identified compound heterozygosity for 2 mutations in the PANK2 gene: a 3-bp deletion (606157.0014) and a 233C-A transversion, resulting in a ser68-to-ter (S68X) substitution. The patient had a severe form of the disorder and died at age 12 years. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PANK2, TYR227CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555787646,
|
|
|
|
|
|
|
|
ClinVar: RCV000544004, RCV002466529
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 20 patients from the Dominican Republic with neurodegeneration with brain iron accumulation-1 (NBIA1; 234200), Delgado et al. (2012) identified a homozygous c.680A-G transition in the PANK2 gene, resulting in a tyr227-to-cys (Y227C) substitution. One homozygous carrier was asymptomatic at 7 years of age ('preclinical' case). Functional studies of the variant were not performed. </p><p>Schiessl-Weyer et al. (2015) examined erythrocyte morphology in 25 patients from the Dominican Republic with PKAN and a homozygous Y227C mutation (c.680A-G, NM_153638.2) in exon 2 of the PANK2 gene, most of whom were previously reported by Delgado et al. (2012). Schiessl-Weyer et al. (2015) noted that PANK2 and other enzymes of the coenzyme A biosynthetic pathway are normal constituents of the erythrocyte cytosol; they hypothesized that reduced CoA levels could result in aberrant lipid-based signaling processes and dysfunctional organization of protein complexes at the erythrocyte plasma membrane. The somewhat later onset of disease in these patients (average 10.8 years), absence of pigmentary retinopathy, and mild or no intellectual decline suggested that the mutant protein likely has some residual enzymatic activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
|
</div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ching, K. H. L., Westaway, S. K., Gitschier, J., Higgins, J. J., Hayflick, S. J.
|
|
<strong>HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration.</strong>
|
|
Neurology 58: 1673-1674, 2002.
|
|
|
|
|
|
[PubMed: 12058097]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.58.11.1673]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Delgado, R. F., Sanchez, P. R., Speckter, H., Then, E. P., Jimenez, R., Oviedo, J., Dellani, P. R., Foerster, B., Stoeter, P.
|
|
<strong>Missense PANK2 mutation without 'eye of the tiger' sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN).</strong>
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Houlden, H., Lincoln, S., Farrer, M., Cleland, P. G., Hardy, J., Orrell, R. W.
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Orrell, R. W., Amrolia, P. J., Heald, A., Cleland, P. G., Owen, J. S., Morgan-Hughes, J. A., Harding, A. E., Marsden, C. D.
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Rump, P., Lemmink, H. H., Verschuuren-Bemelmans, C. C., Grootscholten, P. M., Fock, J. M., Hayflick, S. J., Westaway, S. K., Vos, Y. J., van Essen, A. J.
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<strong>A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect.</strong>
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