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Entry
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- *603604 - PHOSPHOLIPASE A2, GROUP VI; PLA2G6
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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">*603604</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/603604">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000184381;t=ENST00000332509" 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=8398" 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=603604" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000184381;t=ENST00000332509" 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_001004426,NM_001199562,NM_001349864,NM_001349865,NM_001349866,NM_001349867,NM_001349868,NM_001349869,NM_003560" 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_003560" 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=603604" 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=04675&isoform_id=04675_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/PLA2G6" 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/3142700,5305594,5305596,6685712,6983920,30354669,37589885,40846376,47678617,52486194,52486251,57997023,119580623,119580624,158255086,158255860,193788420,221043224,313760592,1169292904,1169292906,1169292908,1169292910,1169292912,1169292915" 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/O60733" 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=8398" 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=ENSG00000184381;t=ENST00000332509" 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=PLA2G6" 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=PLA2G6" 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+8398" 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/PLA2G6" 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:8398" 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/8398" 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=chr22&hgg_gene=ENST00000332509.8&hgg_start=38111495&hgg_end=38181830&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:9039" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:9039" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/pla2g6" 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=603604[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=603604[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/PLA2G6/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000184381" 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=PLA2G6" 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=PLA2G6" 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=PLA2G6" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://grenada.lumc.nl/LOVD2/shared1/home.php?select_db=PLA2G6" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=PLA2G6&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/PA33367" 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:9039" 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/FBgn0036053.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:1859152" 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/PLA2G6#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:1859152" 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/8398/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002105/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=8398" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00012319;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00012319 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00016661;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00016661 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-2079" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:8398" 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=PLA2G6&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> 52713000<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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603604
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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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PHOSPHOLIPASE A2, GROUP VI; PLA2G6
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
PHOSPHOLIPASE A2, CALCIUM-INDEPENDENT; IPLA2<br />
|
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PATATIN-LIKE PHOSPHOLIPASE DOMAIN-CONTAINING PROTEIN 9; PNPLA9<br />
|
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PHOSPHOLIPASE A2, CALCIUM-INDEPENDENT, GROUP VI, A<br />
|
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IPLA2-VIA
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PLA2G6" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PLA2G6</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>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/22/268?start=-3&limit=10&highlight=268">22q13.1</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr22:38111495-38181830&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'})">22:38,111,495-38,181,830</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
|
<div>
|
|
<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>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=256600,610217,612953" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
|
</th>
|
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<p>Phospholipases A2 (PLA2s) catalyze hydrolysis of the sn-2 acyl-ester bonds in phospholipids, leading to the release of arachidonic acid and other fatty acids. PLA2G6 is a calcium-independent PLA2 (<a href="#6" class="mim-tip-reference" title="Larsson Forsell, P. K. A., Kennedy, B. P., Claesson, H.-E. <strong>The human calcium-independent phospholipase A2 gene: multiple enzymes with distinct properties from a single gene.</strong> Europ. J. Biochem. 262: 575-585, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10336645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10336645</a>] [<a href="https://doi.org/10.1046/j.1432-1327.1999.00418.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10336645">Larsson Forsell et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10336645" 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="Tang, J., Kriz, R. W., Wolfman, N., Shaffer, M., Seehra, J., Jones, S. S. <strong>A novel cytosolic calcium-independent phospholipase A(2) contains eight ankyrin motifs.</strong> J. Biol. Chem. 272: 8567-8575, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9079687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9079687</a>] [<a href="https://doi.org/10.1074/jbc.272.13.8567" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9079687">Tang et al. (1997)</a> purified an 85-kD cytosolic calcium-independent PLA2, termed iPLA2, from Chinese hamster ovary (CHO) cells. They isolated a partial human cDNA from a Burkitt lymphoma cDNA library by screening with a CHO cDNA. Northern blot analysis revealed that iPLA2 is expressed in a variety of rodent tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9079687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Larsson, P. K. A., Claesson, H.-E., Kennedy, B. P. <strong>Multiple splice variants of the human calcium-independent phospholipase A(2) and their effect on enzyme activity.</strong> J. Biol. Chem. 273: 207-214, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9417066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9417066</a>] [<a href="https://doi.org/10.1074/jbc.273.1.207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9417066">Larsson et al. (1998)</a> cloned human iPLA2 cDNAs and discovered multiple mRNA isoforms resulting from alternative splicing. The full-length cDNA encodes an 806-amino acid protein with a lipase motif and 8 ankyrin repeats. Human and rodent iPLA2 share 90% overall amino acid sequence identity, with the human sequence differing in containing a 54-residue insertion that would interrupt the last putative ankyrin repeat. Two of the alternatively spliced forms encode only the ankyrin repeat region of the protein. Coexpression of these variants with the active iPLA2 enzyme resulted in a decrease of the enzyme's activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9417066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By computational analysis, <a href="#6" class="mim-tip-reference" title="Larsson Forsell, P. K. A., Kennedy, B. P., Claesson, H.-E. <strong>The human calcium-independent phospholipase A2 gene: multiple enzymes with distinct properties from a single gene.</strong> Europ. J. Biochem. 262: 575-585, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10336645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10336645</a>] [<a href="https://doi.org/10.1046/j.1432-1327.1999.00418.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10336645">Larsson Forsell et al. (1999)</a> identified several human iPLA2 variants that were alternatively spliced at exons 3, 9, 9a, and 10a, as well as part of exon 14. Northern blot analysis detected iPLA2 transcripts of 1.8, 2.0, 3.2, and 4.2 kb. The 2.0-kb variant was expressed at variable levels in all tissues examined, the 3.2-kb and 4.2-kb transcripts were expressed at variable levels in most tissues examined, and the 1.8-kb transcript was expressed predominantly in heart and skeletal muscle, with lower levels in bone marrow. Western blot analysis of fractionated transfected COS-7 cells showed that full-length human iPLA2 associated with membranes. Hydropathy plot and bioinformatic analyses suggested that iPLA2 contains 2 hydrophobic regions that may be transmembrane domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10336645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using rat iPla2 to screen a human insulinoma cDNA library, followed by RT-PCR of human islet RNA, <a href="#8" class="mim-tip-reference" title="Ma, Z., Wang, X., Nowatzke, W., Ramanadham, S., Turk, J. <strong>Human pancreatic islets express mRNA species encoding two distinct catalytically active isoforms of group VI phospholipase A2 (iPLA2) that arise from an exon-skipping mechanism of alternative splicing of the transcript from the iPLA2 gene on chromosome 22q13.1.</strong> J. Biol. Chem. 274: 9607-9616, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10092647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10092647</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10092647[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/10.1074/jbc.274.14.9607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10092647">Ma et al. (1999)</a> cloned long and short iPLA2 splice variants. The short variant lacks an insert encoding a 54-amino acid proline-rich region in the long variant. This insert interrupts the last putative ankyrin repeat and is likely to function as a linker region that separates the N-terminal protein-binding domain from the C-terminal catalytic domain. RT-PCR detected these 2 transcripts in a human promonocytic cell line and in normal islet cells. SDS-PAGE showed that the recombinant short and long isoforms of human iPLA2 had apparent molecular masses of 85 kD and 88 kD, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10092647" 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="Larsson Forsell, P. K. A., Kennedy, B. P., Claesson, H.-E. <strong>The human calcium-independent phospholipase A2 gene: multiple enzymes with distinct properties from a single gene.</strong> Europ. J. Biochem. 262: 575-585, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10336645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10336645</a>] [<a href="https://doi.org/10.1046/j.1432-1327.1999.00418.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10336645">Larsson Forsell et al. (1999)</a> determined that the PLA2G6 gene contains 19 exons, including the alternative exons 9a and 10a, and spans more than 69 kb. The promoter region lacks a TATA box, but contains a CpG island and several potential SP1 (<a href="/entry/189906">189906</a>)-binding sites. The 5-prime flanking region also contains an inverted MER53 sequence and an Alu element. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10336645" 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="Ma, Z., Wang, X., Nowatzke, W., Ramanadham, S., Turk, J. <strong>Human pancreatic islets express mRNA species encoding two distinct catalytically active isoforms of group VI phospholipase A2 (iPLA2) that arise from an exon-skipping mechanism of alternative splicing of the transcript from the iPLA2 gene on chromosome 22q13.1.</strong> J. Biol. Chem. 274: 9607-9616, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10092647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10092647</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10092647[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/10.1074/jbc.274.14.9607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10092647">Ma et al. (1999)</a> mapped the PLA2G6 gene to chromosome 22q13.1 by FISH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10092647" 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="Tang, J., Kriz, R. W., Wolfman, N., Shaffer, M., Seehra, J., Jones, S. S. <strong>A novel cytosolic calcium-independent phospholipase A(2) contains eight ankyrin motifs.</strong> J. Biol. Chem. 272: 8567-8575, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9079687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9079687</a>] [<a href="https://doi.org/10.1074/jbc.272.13.8567" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9079687">Tang et al. (1997)</a> found that expression of the hamster iPla2 cDNA generated an active 85-kD protein that selectively hydrolyzed sn-2 over sn-1 fatty acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9079687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Larsson Forsell, P. K. A., Kennedy, B. P., Claesson, H.-E. <strong>The human calcium-independent phospholipase A2 gene: multiple enzymes with distinct properties from a single gene.</strong> Europ. J. Biochem. 262: 575-585, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10336645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10336645</a>] [<a href="https://doi.org/10.1046/j.1432-1327.1999.00418.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10336645">Larsson Forsell et al. (1999)</a> found that COS-7 cells expressing full-length human iPLA2 and rat vascular smooth muscle cells showed Ca(2+)-independent release of arachidonic acid from radiolabeled phospholipids, and that the activity was associated with the membrane fractions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10336645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Ma, Z., Wang, X., Nowatzke, W., Ramanadham, S., Turk, J. <strong>Human pancreatic islets express mRNA species encoding two distinct catalytically active isoforms of group VI phospholipase A2 (iPLA2) that arise from an exon-skipping mechanism of alternative splicing of the transcript from the iPLA2 gene on chromosome 22q13.1.</strong> J. Biol. Chem. 274: 9607-9616, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10092647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10092647</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10092647[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/10.1074/jbc.274.14.9607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10092647">Ma et al. (1999)</a> found that both recombinant short and long isoforms of human iPLA2 had Ca(2+)-independent PLA2 activity in cytosolic and membrane fractions. Their activities were inhibited by bromoenol lactone, an iPLA2 suicide substrate. The long iPLA2 isoform, but not the short isoform, was activated by ATP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10092647" 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="#17" class="mim-tip-reference" title="Turk, J., Ramanadham, S. <strong>The expression and function of a group VIA calcium-independent phospholipase A2 (iPLA2-beta) in beta-cells.</strong> Canad. J. Physiol. Pharm. 82: 824-832, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15573142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15573142</a>] [<a href="https://doi.org/10.1139/y04-064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15573142">Turk and Ramanadham (2004)</a> stated that the shorter iPLA2 isoforms that lack the C-terminal catalytic domain function as negative modulators of iPLA2-beta, the full-length isoform. They also noted that iPLA2-beta can be proteolytically processed to yield truncated products that are constitutively active. <a href="#17" class="mim-tip-reference" title="Turk, J., Ramanadham, S. <strong>The expression and function of a group VIA calcium-independent phospholipase A2 (iPLA2-beta) in beta-cells.</strong> Canad. J. Physiol. Pharm. 82: 824-832, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15573142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15573142</a>] [<a href="https://doi.org/10.1139/y04-064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15573142">Turk and Ramanadham (2004)</a> reviewed the role of iPLA2 in phospholipid remodeling, signal transduction, cell proliferation, and endoplasmic reticulum stress-mediated apoptosis. They stated that, in pancreatic islets, beta cells, and insulinoma cells, iPLA2-beta participates in glucose-stimulated insulin secretion, but it is not involved in membrane phospholipid remodeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15573142" 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>Arachidonic acid and its metabolites are involved in regulation of endothelial cell proliferation. <a href="#4" class="mim-tip-reference" title="Herbert, S. P., Walker, J. H. <strong>Group VIA calcium-independent phospholipase A2 mediates endothelial cell S phase progression.</strong> J. Biol. Chem. 281: 35709-35716, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16966332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16966332</a>] [<a href="https://doi.org/10.1074/jbc.M600699200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16966332">Herbert and Walker (2006)</a> showed that bromoenol lactone-mediated inhibition of iPLA2-VIA activity in human endothelial cells blocked endothelial cell growth and inhibited DNA synthesis in a dose-dependent manner. These effects were reversed upon the exogenous addition of arachidonic acid. iPLA2-VIA activity was required for expression of the cyclin A (see CCNA1; <a href="/entry/604036">604036</a>)/CDK2 (<a href="/entry/116953">116953</a>) complex, and thus inhibition of iPLA2-VIA blocked S phase progression and resulted in exit from the cell cycle. Inhibition of iPLA2-VIA-mediated endothelial cell proliferation was sufficient to block angiogenic tubule formation by human endothelial cells cocultured with human dermal fibroblasts. <a href="#4" class="mim-tip-reference" title="Herbert, S. P., Walker, J. H. <strong>Group VIA calcium-independent phospholipase A2 mediates endothelial cell S phase progression.</strong> J. Biol. Chem. 281: 35709-35716, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16966332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16966332</a>] [<a href="https://doi.org/10.1074/jbc.M600699200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16966332">Herbert and Walker (2006)</a> concluded that, by generating arachidonic acid, iPLA2-VIA regulates endothelial cell S phase progression, cell cycle residence, and angiogenesis. They noted that iPLA2-VIA is involved in cell growth and division in other cell types through arachidonic acid-independent regulation of glycerophospholipid metabolism during the cell cycle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16966332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Neurodegeneration with Brain Iron Accumulation 2A and 2B and Karak Syndrome</em></strong></p><p>
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In studies of 12 families with infantile neuroaxonal dystrophy (INAD, NBIA2A; <a href="/entry/256600">256600</a>) and a large consanguineous Pakistani family with neurodegeneration with brain iron accumulation (NBIA2B; <a href="/entry/610217">610217</a>), <a href="#11" class="mim-tip-reference" title="Morgan, N. V., Westaway, S. K., Morton, J. E. V., Gregory, A., Gissen, P., Sonek, S., Cangul, H., Coryell, J., Canham, N., Nardocci, N., Zorzi, G., Pasha, S., and 15 others. <strong>PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.</strong> Nature Genet. 38: 752-754, 2006. Note: Erratum: Nature Genet. 38: 957 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16783378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16783378</a>] [<a href="https://doi.org/10.1038/ng1826" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16783378">Morgan et al. (2006)</a> mapped a novel INAD locus to 22q12.3-q13.2 (lod score 4.78), with evidence of locus heterogeneity. They also detected linkage to 22q12-q13 in a family with NBIA (lod score 4.65) suggesting allelism. After sequencing 70 of the approximately 100 positional candidate genes, they detected mutations in PLA2G6 in 4 kindreds, including the Pakistani family with NBIA2B and 3 INAD probands (<a href="#0001">603604.0001</a>-<a href="#0005">603604.0005</a>). They also identified PLA2G6 mutations in 28 additional probands with INAD and in the original family with Karak syndrome and high basal ganglia iron (see <a href="/entry/610217">610217</a>). In all, they identified 44 unique mutations (32 missense, 5 deletions leading to frameshift, 3 nonsense, 2 leading to amino acid deletions without frameshift, 1 splice site, and 1 large deletion). Of the missense mutations, 85% occurred at amino acid positions that are conserved in vertebrates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16783378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an independent study, <a href="#5" class="mim-tip-reference" title="Khateeb, S., Flusser, H., Ofir, R., Shelef, I., Narkis, G., Vardi, G., Shorer, Z., Levy, R., Galil, A., Elbedour, K., Birk, O. S. <strong>PLA2G6 mutation underlies infantile neuroaxonal dystrophy.</strong> Am. J. Hum. Genet. 79: 942-948, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033970</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033970[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033970">Khateeb et al. (2006)</a> identified a homozygous mutation in PLA2G6 in 2 consanguineous Israeli Bedouin kindreds with infantile neuroaxonal dystrophy (NBIA2A). The 3-bp deletion (<a href="#0004">603604.0004</a>) resulted in the deletion of valine-691. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033970" 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="Gregory, A., Westaway, S. K., Holm, I. E., Kotzbauer, P. T., Hogarth, P., Sonek, S., Coryell, J. C., Nguyen, T. M., Nardocci, N., Zorzi, G., Rodriguez, D., Desguerre, I., and 10 others. <strong>Neurodegeneration associated with genetic defects in phospholipase A(2).</strong> Neurology 71: 1402-1409, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18799783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18799783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18799783[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/10.1212/01.wnl.0000327094.67726.28" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18799783">Gregory et al. (2008)</a> found PLA2G6 mutations in 45 (79%) of 56 patients with INAD1 (NBIA2A) and in 6 (20%) of 23 patients with idiopathic NBIA2B (see, e.g., <a href="#0006">603604.0006</a>-<a href="#0008">603604.0008</a>). No PLA2G6 mutations were found in 11 patients with clinical evidence of INAD, including 5 in whom spheroids were reported on peripheral nerve biopsy. All 28 patients with 2 null mutations or homozygous for any mutation had early onset and rapidly progressive disease. Patients with the less severe phenotype of NBIA tended to have compound heterozygous missense mutations, consistent with residual protein function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18799783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Parkinson Disease 14</em></strong></p><p>
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In 2 unrelated families with adult-onset dystonia-parkinsonism (PARK14; <a href="/entry/612953">612953</a>), <a href="#12" class="mim-tip-reference" title="Paisan-Ruiz, C., Bhatia, K. P., Li, A., Hernandez, D., Davis, M., Wood, N. W., Hardy, J., Houlden, H., Singleton, A., Schneider, S. A. <strong>Characterization of PLA2G6 as a locus for dystonia-parkinsonism.</strong> Ann. Neurol. 65: 19-23, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18570303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18570303</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18570303[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18570303">Paisan-Ruiz et al. (2009)</a> identified 2 different homozygous mutations in the PLA2G6 gene (R741Q; <a href="#0009">603604.0009</a> and R747W; <a href="#0010">603604.0010</a>, respectively). The disorder was characterized by rapidly progressive cognitive decline, bradykinesia, rigidity, and dystonia. None of the 3 affected patients had evidence of brain iron accumulation. The authors emphasized that PLA2G6 mutations should be considered in patients with neurodegeneration even without brain iron on MRI scan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18570303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Magrinelli, F., Mehta, S., Di Lazzaro, G., Latorre, A., Edwards, M. J., Balint, B., Basu, P., Kobylecki, C., Groppa, S., Hegde, A., Mulroy, E., Estevez-Fraga, C., and 13 others. <strong>Dissecting the phenotype of PLA2G6-related parkinsonism.</strong> Mov. Disord. 37: 148-161, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34622992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34622992</a>] [<a href="https://doi.org/10.1002/mds.28807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34622992">Magrinelli et al. (2022)</a> reported 14 new patients from 12 families with PARK14 and performed a systematic search for patients with PARK14 in the literature, identifying a total of 86 patients from 68 families, including their own. Parental consanguinity was seen in 55% of families. Homozygosity for mutations in the PLA2G6 gene was seen in 46/86 (53.5%), with compound heterozygosity in 40/86 (46.5%). A total of 54 mutations in PLA2G6 have been associated with parkinsonism, including 4 novel variants in the newly reported patients. Among the 54 mutations, 44 were missense, 2 were in-frame deletions, 4 were splicing, 2 were nonsense, and 2 were frameshift mutations. The most commonly observed mutations were D331Y (<a href="#0016">603604.0016</a>), seen in 17 families, mainly from China and Taiwan, and R741Q (<a href="#0009">603604.0009</a>), seen in 12 families from India, Pakistan, and Saudi Arabia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34622992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a systematic review of 86 patients from 68 families with PARK14, <a href="#9" class="mim-tip-reference" title="Magrinelli, F., Mehta, S., Di Lazzaro, G., Latorre, A., Edwards, M. J., Balint, B., Basu, P., Kobylecki, C., Groppa, S., Hegde, A., Mulroy, E., Estevez-Fraga, C., and 13 others. <strong>Dissecting the phenotype of PLA2G6-related parkinsonism.</strong> Mov. Disord. 37: 148-161, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34622992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34622992</a>] [<a href="https://doi.org/10.1002/mds.28807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34622992">Magrinelli et al. (2022)</a> found that most mutations were nontruncating, which might be less detrimental to protein function than the truncating mutations involved with infantile neuroaxonal dystrophy. Based on limited biochemical and enzymatic studies, the authors suggested that mutations associated with NBIA2A and NBIA2B result in loss of enzyme activity, whereas those associated with PARK14 do not impair phospholipase or lysophospholipase catalytic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34622992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Bao, S., Miller, D. J., Ma, Z., Wohltmann, M., Eng, G., Ramanadham, S., Moley, K., Turk, J. <strong>Male mice that do not express group VIA phospholipase A(2) produce spermatozoa with impaired motility and have greatly reduced fertility.</strong> J. Biol. Chem. 279: 38194-38200, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15252026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15252026</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15252026[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/10.1074/jbc.M406489200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15252026">Bao et al. (2004)</a> obtained Ipla2-beta-null mice at a mendelian ratio. They found that spermatozoa from Ipla2-beta -/- mice had reduced motility and impaired ability to fertilize mouse oocytes in vitro and in vivo. Female Ipla2-beta -/- mice had nearly normal fertility. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15252026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Ramanadham, S., Yarasheski, K. E., Silva, M. J., Wohltmann, M., Novack, D. V., Christiansen, B., Tu, X., Zhang, S., Lei, X., Turk, J. <strong>Age-related changes in bone morphology are accelerated in group VIA phospholipase A2 (iPLA2-beta)-null mice.</strong> Am. J. Path. 172: 868-881, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18349124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18349124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18349124[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/10.2353/ajpath.2008.070756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18349124">Ramanadham et al. (2008)</a> found that Ipla2-beta-null mice had cortical bone size, trabecular bone volume, bone mineralizing surfaces, and bone strength similar to wildtype mice at 3 months of age. Both groups showed declines in these measures with age, but the decline was more pronounced in Ipla2-beta-null mice. The lower bone mass in Ipla2-beta-null mice was accompanied by an increase in bone marrow fat. Relative to wildtype mice, undifferentiated bone marrow stromal cells from knockout mice expressed higher levels of Pparg (<a href="/entry/601487">601487</a>) and lower levels of Runx2 (<a href="/entry/600211">600211</a>) mRNA, and these changes correlated with increased adipogenesis and decreased osteogenesis in bone marrow stromal cells in knockout mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18349124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Malik, I., Turk, J., Mancuso, D. J., Montier, L., Wohltmann, M., Wozniak, D. F., Schmidt, R. E., Gross, R. W., Kotzbauer, P. T. <strong>Disrupted membrane homeostasis and accumulation of ubiquitinated proteins in a mouse model of infantile neuroaxonal dystrophy caused by PLA2G6 mutations.</strong> Am. J. Path. 172: 406-416, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18202189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18202189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18202189[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/10.2353/ajpath.2008.070823" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18202189">Malik et al. (2008)</a> found that Pla2g6-null mice developed age-dependent neurologic impairment that was evident in rotarod, balance, and climbing tests by 13 months of age. Neuropathologic analysis showed numerous spheroids in the brain similar to those observed in human INAD. Spheroids contained tubulovesicular membranes and stained strongly with anti-ubiquitin antibodies. Onset of motor impairment correlated with increased spheroids throughout the neuropil in nearly all brain regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18202189" 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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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>16 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603604[MIM]" class="btn btn-default mim-tip-hint" role="button" 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>
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<strong>.0001 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</strong>
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PLA2G6, TYR790TER
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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> rs121908680 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908680;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/rs121908680?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=rs121908680" 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=rs121908680" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a proband with classic infantile neuroaxonal dystrophy (NBIA2A; <a href="/entry/256600">256600</a>), <a href="#11" class="mim-tip-reference" title="Morgan, N. V., Westaway, S. K., Morton, J. E. V., Gregory, A., Gissen, P., Sonek, S., Cangul, H., Coryell, J., Canham, N., Nardocci, N., Zorzi, G., Pasha, S., and 15 others. <strong>PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.</strong> Nature Genet. 38: 752-754, 2006. Note: Erratum: Nature Genet. 38: 957 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16783378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16783378</a>] [<a href="https://doi.org/10.1038/ng1826" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16783378">Morgan et al. (2006)</a> identified a 2370T-G transversion in exon 17 of the PLA2G6 gene that was predicted to result in a premature termination in the protein (tyr790 to stop; Y790X). The parents were known to be consanguineous and the mutation was present in homozygous state. The presence of spheroids had been demonstrated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16783378" 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> rs121908681 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908681;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/rs121908681?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=rs121908681" 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=rs121908681" 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=RCV000006573 OR RCV001003639 OR RCV001542712 OR RCV003319301" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006573, RCV001003639, RCV001542712, RCV003319301" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006573...</a>
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<p>In a large consanguineous Pakistani family with neurodegeneration with brain iron accumulation-2B (NBIA2B; <a href="/entry/610217">610217</a>), <a href="#11" class="mim-tip-reference" title="Morgan, N. V., Westaway, S. K., Morton, J. E. V., Gregory, A., Gissen, P., Sonek, S., Cangul, H., Coryell, J., Canham, N., Nardocci, N., Zorzi, G., Pasha, S., and 15 others. <strong>PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.</strong> Nature Genet. 38: 752-754, 2006. Note: Erratum: Nature Genet. 38: 957 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16783378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16783378</a>] [<a href="https://doi.org/10.1038/ng1826" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16783378">Morgan et al. (2006)</a> identified homozygosity for a missense mutation in exon 12 of the PLA2G6 gene, a 1634A-C transversion that resulted in a lys545-to-thr substitution (K545T). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16783378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</strong>
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PLA2G6, VAL310GLU
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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> rs121908682 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908682;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/rs121908682?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=rs121908682" 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=rs121908682" 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=RCV000006574 OR RCV002512835" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006574, RCV002512835" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006574...</a>
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<p>In a case of classic infantile neuroaxonal dystrophy (NBIA2A; <a href="/entry/256600">256600</a>), <a href="#11" class="mim-tip-reference" title="Morgan, N. V., Westaway, S. K., Morton, J. E. V., Gregory, A., Gissen, P., Sonek, S., Cangul, H., Coryell, J., Canham, N., Nardocci, N., Zorzi, G., Pasha, S., and 15 others. <strong>PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.</strong> Nature Genet. 38: 752-754, 2006. Note: Erratum: Nature Genet. 38: 957 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16783378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16783378</a>] [<a href="https://doi.org/10.1038/ng1826" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16783378">Morgan et al. (2006)</a> described a 929T-A transversion in exon 7 of the PLA2G6 gene, predicted to result in a val310-to-glu (V310E) amino acid change in the protein. The mutation was present in homozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16783378" 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 2A</strong>
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PLA2G6, 3-BP DEL, 2070TGT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587784343 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587784343;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=rs587784343" 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=rs587784343" 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=RCV000006575 OR RCV000147311 OR RCV000480455 OR RCV000761526 OR RCV001523781" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006575, RCV000147311, RCV000480455, RCV000761526, RCV001523781" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006575...</a>
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<p>In a case of classic infantile neuroaxonal dystrophy (NBIA2A; <a href="/entry/256600">256600</a>), <a href="#11" class="mim-tip-reference" title="Morgan, N. V., Westaway, S. K., Morton, J. E. V., Gregory, A., Gissen, P., Sonek, S., Cangul, H., Coryell, J., Canham, N., Nardocci, N., Zorzi, G., Pasha, S., and 15 others. <strong>PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.</strong> Nature Genet. 38: 752-754, 2006. Note: Erratum: Nature Genet. 38: 957 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16783378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16783378</a>] [<a href="https://doi.org/10.1038/ng1826" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16783378">Morgan et al. (2006)</a> found a 3-bp deletion in exon 15 of the PLA2G6 gene, 2070_2072delTGT, resulting in deletion of val691 from the protein (V691del). The mutation was present in homozygous state, or possibly hemizygous state because of deletion of 1 allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16783378" 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 consanguineous Bedouin kindred with cases of infantile neuroaxonal dystrophy in 3 separate sibships and in another kindred with a single affected individual, <a href="#5" class="mim-tip-reference" title="Khateeb, S., Flusser, H., Ofir, R., Shelef, I., Narkis, G., Vardi, G., Shorer, Z., Levy, R., Galil, A., Elbedour, K., Birk, O. S. <strong>PLA2G6 mutation underlies infantile neuroaxonal dystrophy.</strong> Am. J. Hum. Genet. 79: 942-948, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033970</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033970[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508572" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033970">Khateeb et al. (2006)</a> found the same 3-nucleotide deletion. The mutation was also found in heterozygosity in a single individual among 300 unrelated Bedouin controls. Both affected families and the unrelated carrier had the same haplotype surrounding the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 KARAK SYNDROME</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> rs121908683 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908683;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/rs121908683?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=rs121908683" 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=rs121908683" 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=RCV000006576 OR RCV001092011 OR RCV001582469 OR RCV002512836 OR RCV003507245 OR RCV005031400" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006576, RCV001092011, RCV001582469, RCV002512836, RCV003507245, RCV005031400" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006576...</a>
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<p>In the original family with Karak syndrome (see <a href="/entry/610217">610217</a>), <a href="#11" class="mim-tip-reference" title="Morgan, N. V., Westaway, S. K., Morton, J. E. V., Gregory, A., Gissen, P., Sonek, S., Cangul, H., Coryell, J., Canham, N., Nardocci, N., Zorzi, G., Pasha, S., and 15 others. <strong>PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.</strong> Nature Genet. 38: 752-754, 2006. Note: Erratum: Nature Genet. 38: 957 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16783378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16783378</a>] [<a href="https://doi.org/10.1038/ng1826" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16783378">Morgan et al. (2006)</a> detected homozygosity for a C-to-T transition at nucleotide 1894 in exon 14 of the PLA2G6 gene that resulted in a substitution of trp for arg at codon 632 (R632W). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16783378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</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> rs121908680 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908680;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/rs121908680?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=rs121908680" 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=rs121908680" 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=RCV000006572 OR RCV000147321 OR RCV000323935 OR RCV000623021 OR RCV000763481 OR RCV000778661 OR RCV001250474 OR RCV001333134 OR RCV001813959 OR RCV002265549 OR RCV003407288" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006572, RCV000147321, RCV000323935, RCV000623021, RCV000763481, RCV000778661, RCV001250474, RCV001333134, RCV001813959, RCV002265549, RCV003407288" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006572...</a>
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<p>In 4 patients with infantile neuroaxonal dystrophy (NBIA2A; <a href="/entry/256600">256600</a>), <a href="#3" class="mim-tip-reference" title="Gregory, A., Westaway, S. K., Holm, I. E., Kotzbauer, P. T., Hogarth, P., Sonek, S., Coryell, J. C., Nguyen, T. M., Nardocci, N., Zorzi, G., Rodriguez, D., Desguerre, I., and 10 others. <strong>Neurodegeneration associated with genetic defects in phospholipase A(2).</strong> Neurology 71: 1402-1409, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18799783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18799783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18799783[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/10.1212/01.wnl.0000327094.67726.28" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18799783">Gregory et al. (2008)</a> identified a homozygous 2370T-G transversion in the PLA2G6 gene, resulting in a tyr790-to-ter (Y790X) substitution. The INAD1 phenotype was characterized by early onset of psychomotor regression with truncal hypotonia and rapid progression to tetraparesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18799783" 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>.0007 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</strong>
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NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2B, INCLUDED
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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> rs587784353 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587784353;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/rs587784353?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=rs587784353" 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=rs587784353" 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=RCV000006578 OR RCV000006579 OR RCV000147322 OR RCV000255768 OR RCV002504755 OR RCV002512837 OR RCV002512838" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006578, RCV000006579, RCV000147322, RCV000255768, RCV002504755, RCV002512837, RCV002512838" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006578...</a>
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<p><strong><em>Neurodegeneration with Brain Iron Accumulation 2A</em></strong></p><p>
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In a patient with infantile neuroaxonal dystrophy (NBIA2A; <a href="/entry/256600">256600</a>), <a href="#3" class="mim-tip-reference" title="Gregory, A., Westaway, S. K., Holm, I. E., Kotzbauer, P. T., Hogarth, P., Sonek, S., Coryell, J. C., Nguyen, T. M., Nardocci, N., Zorzi, G., Rodriguez, D., Desguerre, I., and 10 others. <strong>Neurodegeneration associated with genetic defects in phospholipase A(2).</strong> Neurology 71: 1402-1409, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18799783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18799783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18799783[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/10.1212/01.wnl.0000327094.67726.28" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18799783">Gregory et al. (2008)</a> identified a homozygous 2-bp deletion (2370delTG) in the PLA2G6 gene, which resulted in premature termination at codon 790 similar to the Y790X mutation (<a href="#0006">603604.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18799783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Neurodegeneration with Brain Iron Accumulation 2B</em></strong></p><p>
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In a patient with neurodegeneration with brain iron accumulation-2B (NBIA2B; <a href="/entry/610217">610217</a>), <a href="#3" class="mim-tip-reference" title="Gregory, A., Westaway, S. K., Holm, I. E., Kotzbauer, P. T., Hogarth, P., Sonek, S., Coryell, J. C., Nguyen, T. M., Nardocci, N., Zorzi, G., Rodriguez, D., Desguerre, I., and 10 others. <strong>Neurodegeneration associated with genetic defects in phospholipase A(2).</strong> Neurology 71: 1402-1409, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18799783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18799783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18799783[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/10.1212/01.wnl.0000327094.67726.28" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18799783">Gregory et al. (2008)</a> identified compound heterozygosity for the 2370delTG mutation and a 238G-A transition, resulting in an ala80-to-thr (A80T; <a href="#0007">603604.0007</a>) substitution. The patient presented at 3 years of age with toe walking and lower extremity spasticity. She developed optic atrophy and became nonambulatory by 5 years of age with dystonia and dysarthria, progressing to profound sensorimotor impairment by age 9 years. She died at age 23 years. Postmortem examination showed neuronal loss, axonal swelling, and Lewy bodies and neurofibrillary tangles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18799783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2B</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> rs121908685 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908685;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/rs121908685?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=rs121908685" 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=rs121908685" 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=RCV000006580 OR RCV000535771 OR RCV000660638 OR RCV001540404 OR RCV002512839" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006580, RCV000535771, RCV000660638, RCV001540404, RCV002512839" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006580...</a>
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<p>For discussion of the ala80-to-thr (A80T) mutation in the PLA2G6 gene that was found in compound heterozygous state in a patient with neurodegeneration with brain iron accumulation-2B (NBIA2B; <a href="/entry/610217">610217</a>) by <a href="#3" class="mim-tip-reference" title="Gregory, A., Westaway, S. K., Holm, I. E., Kotzbauer, P. T., Hogarth, P., Sonek, S., Coryell, J. C., Nguyen, T. M., Nardocci, N., Zorzi, G., Rodriguez, D., Desguerre, I., and 10 others. <strong>Neurodegeneration associated with genetic defects in phospholipase A(2).</strong> Neurology 71: 1402-1409, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18799783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18799783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18799783[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/10.1212/01.wnl.0000327094.67726.28" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18799783">Gregory et al. (2008)</a>, see <a href="#0007">603604.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18799783" 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> rs121908686 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908686;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/rs121908686?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=rs121908686" 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=rs121908686" 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=RCV000006581 OR RCV000811054 OR RCV001251187 OR RCV001588801 OR RCV002496284 OR RCV003155018" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006581, RCV000811054, RCV001251187, RCV001588801, RCV002496284, RCV003155018" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006581...</a>
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<p>In 2 affected first cousins from a large consanguineous Indian kindred segregating adult-onset dystonia-parkinsonism (PARK14; <a href="/entry/612953">612953</a>), <a href="#12" class="mim-tip-reference" title="Paisan-Ruiz, C., Bhatia, K. P., Li, A., Hernandez, D., Davis, M., Wood, N. W., Hardy, J., Houlden, H., Singleton, A., Schneider, S. A. <strong>Characterization of PLA2G6 as a locus for dystonia-parkinsonism.</strong> Ann. Neurol. 65: 19-23, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18570303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18570303</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18570303[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18570303">Paisan-Ruiz et al. (2009)</a> identified a homozygous 2222G-A transition in the PLA2G6 gene, resulting in an arg741-to-gln (R741Q) substitution in a conserved residue. Both had onset at age 26 years of a rapidly progressive neurodegenerative disorder characterized by rapid cognitive decline, bradykinesia, tremor and imbalance, eventually leading to loss of mobility. Although <a href="#12" class="mim-tip-reference" title="Paisan-Ruiz, C., Bhatia, K. P., Li, A., Hernandez, D., Davis, M., Wood, N. W., Hardy, J., Houlden, H., Singleton, A., Schneider, S. A. <strong>Characterization of PLA2G6 as a locus for dystonia-parkinsonism.</strong> Ann. Neurol. 65: 19-23, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18570303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18570303</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18570303[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18570303">Paisan-Ruiz et al. (2009)</a> noted that brain MRI showed no evidence of brain iron accumulation, <a href="#2" class="mim-tip-reference" title="Gregory, A., Polster, B. J., Hayflick, S. J. <strong>Clinical and genetic delineation of neurodegeneration with brain iron accumulation.</strong> J. Med. Genet. 46: 73-80, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18981035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18981035</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18981035[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/10.1136/jmg.2008.061929" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18981035">Gregory et al. (2009)</a> stated that this disorder could be considered under the umbrella designation of atypical neurodegeneration with brain iron accumulation (NBIA). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18981035+18570303" 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> rs121908687 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908687;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/rs121908687?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=rs121908687" 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=rs121908687" 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=RCV000006582 OR RCV000763482 OR RCV001268312 OR RCV002512840 OR RCV003507246" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006582, RCV000763482, RCV001268312, RCV002512840, RCV003507246" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006582...</a>
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<p>In a Pakistani man, born of consanguineous parents, with adult-onset dystonia-parkinsonism (PARK14; <a href="/entry/612953">612953</a>), <a href="#12" class="mim-tip-reference" title="Paisan-Ruiz, C., Bhatia, K. P., Li, A., Hernandez, D., Davis, M., Wood, N. W., Hardy, J., Houlden, H., Singleton, A., Schneider, S. A. <strong>Characterization of PLA2G6 as a locus for dystonia-parkinsonism.</strong> Ann. Neurol. 65: 19-23, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18570303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18570303</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18570303[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18570303">Paisan-Ruiz et al. (2009)</a> identified a homozygous 2239C-T transition in the PLA2G6 gene, resulting in an arg747-to-trp (R747W) substitution in a conserved region. The patient had onset at age 18 years of rapid cognitive decline with personality changes, foot dystonia, parkinsonism, and spasticity. Although <a href="#12" class="mim-tip-reference" title="Paisan-Ruiz, C., Bhatia, K. P., Li, A., Hernandez, D., Davis, M., Wood, N. W., Hardy, J., Houlden, H., Singleton, A., Schneider, S. A. <strong>Characterization of PLA2G6 as a locus for dystonia-parkinsonism.</strong> Ann. Neurol. 65: 19-23, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18570303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18570303</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18570303[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.21415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18570303">Paisan-Ruiz et al. (2009)</a> noted that brain MRI showed no evidence of brain iron accumulation, <a href="#2" class="mim-tip-reference" title="Gregory, A., Polster, B. J., Hayflick, S. J. <strong>Clinical and genetic delineation of neurodegeneration with brain iron accumulation.</strong> J. Med. Genet. 46: 73-80, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18981035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18981035</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18981035[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/10.1136/jmg.2008.061929" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18981035">Gregory et al. (2009)</a> stated that this disorder could be considered under the umbrella designation of atypical neurodegeneration with brain iron accumulation (NBIA). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18981035+18570303" 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> rs387906863 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906863;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/rs387906863?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=rs387906863" 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=rs387906863" 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=RCV000023314 OR RCV000779372 OR RCV002273936 OR RCV002477008 OR RCV002513186" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023314, RCV000779372, RCV002273936, RCV002477008, RCV002513186" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023314...</a>
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<p>In 3 Japanese patients, including 2 sibs, with early-onset Parkinson disease-14 (PARK14; <a href="/entry/612953">612953</a>), <a href="#18" class="mim-tip-reference" title="Yoshino, H., Tomiyama, H., Tachibana, N., Ogaki, K., Li, Y., Funayama, M., Hashimoto, T., Takashima, S., Hattori, N. <strong>Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism.</strong> Neurology 75: 1356-1361, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20938027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20938027</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181f73649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20938027">Yoshino et al. (2010)</a> identified compound heterozygosity for 2 mutations in the PLA2G6 gene. All 3 patients carried a 1904G-A transition, resulting in an arg635-to-gln (R635Q) substitution in the catalytic domain. The 2 sibs also had a heterozygous 1354C-T transition, resulting in a gln452-to-ter (Q452X; <a href="#0012">603604.0012</a>) substitution, and the third unrelated patient had a heterozygous 216C-A transversion, resulting in a phe72-to-leu (F72L; <a href="#0013">603604.0013</a>) substitution. Haplotype analysis suggested a founder effect for the R635Q mutation. All 3 patients had onset before age 30 years of L-DOPA-responsive parkinsonism with varying degrees of cognitive decline and frontotemporal lobar atrophy. Brain MRI of 1 patient showed iron accumulation in the substantia nigra and striatum. None of the parents with heterozygous mutations had signs of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20938027" 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> rs387906864 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906864;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/rs387906864?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=rs387906864" 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=rs387906864" 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=RCV000023315" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023315" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023315</a>
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<p>For discussion of the gln452-to-ter (Q452X) mutation in the PLA2G6 gene that was found in compound heterozygous state in 2 sibs with early-onset Parkinson disease-14 (PARK14; <a href="/entry/612953">612953</a>) by <a href="#18" class="mim-tip-reference" title="Yoshino, H., Tomiyama, H., Tachibana, N., Ogaki, K., Li, Y., Funayama, M., Hashimoto, T., Takashima, S., Hattori, N. <strong>Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism.</strong> Neurology 75: 1356-1361, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20938027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20938027</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181f73649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20938027">Yoshino et al. (2010)</a>, see <a href="#0011">603604.0011</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20938027" 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> rs774631197 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs774631197;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/rs774631197?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=rs774631197" 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=rs774631197" 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=RCV000023316" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023316" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023316</a>
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<p>For discussion of the phe72-to-leu (F72L) mutation in the PLA2G6 gene that was found in compound heterozygous state in a patient with early-onset Parkinson disease-14 (PARK14; <a href="/entry/612953">612953</a>) by <a href="#18" class="mim-tip-reference" title="Yoshino, H., Tomiyama, H., Tachibana, N., Ogaki, K., Li, Y., Funayama, M., Hashimoto, T., Takashima, S., Hattori, N. <strong>Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism.</strong> Neurology 75: 1356-1361, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20938027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20938027</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181f73649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20938027">Yoshino et al. (2010)</a>, see <a href="#0011">603604.0011</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20938027" 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>.0014 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</strong>
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PLA2G6, 6.6-KB DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023317" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023317" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023317</a>
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<p>In a patient with infantile neuroaxonal dystrophy (NBIA2A; <a href="/entry/256600">256600</a>), <a href="#16" class="mim-tip-reference" title="Tonelli, A., Romaniello, R., Grasso, R., Cavallini, A., Righini, A., Bresolin, N., Borgatti, R., Bassi, M. T. <strong>Novel splice-site mutations and a large intragenic deletion in PLA2G6 associated with a severe and rapidly progressive form of infantile neuroaxonal dystrophy.</strong> Clin. Genet. 78: 432-440, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20584031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20584031</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01417.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20584031">Tonelli et al. (2010)</a> identified compound heterozygosity for 2 mutations in the PLA2G6 gene: a 6.6-kb deletion from intron 4 to 6, resulting in an in-frame deletion and removal of exons 5 and 6 and a large portion of the ankyrin repeats motif, and a 109C-T transition in exon 2 resulting in an arg37-to-ter (R37X; <a href="#0015">603604.0015</a>) substitution. Analysis of the deletion junction in the first mutation showed that both breakpoints occurred within AluY sequences, suggesting that the deletion was likely mediated by nonallelic homologous recombination (NAHR). The mutations were predicted to result in an almost complete lack of enzyme activity, although a gain of function could not be excluded. The patient had a severe and rapidly progressive disease course, with onset before age 12 months, hypotonia, severe developmental delay with mental retardation, and no eye contact. Spastic tetraparesis developed by age 18 months. Skin biopsy showed axonal spheroids. Although brain iron accumulation was not present, MRI at age 20 months showed hyperintensities on T2-weighted imaging in the caudate and putamen, suggesting an early degeneration process. Brain MRI at age 3 years showed cerebellar cortical atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20584031" 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>.0015 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</strong>
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PLA2G6, ARG37TER
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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> rs200075782 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200075782;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/rs200075782?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=rs200075782" 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=rs200075782" 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=RCV000023318 OR RCV000147282 OR RCV000255026 OR RCV002513187 OR RCV003105777 OR RCV005031452" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023318, RCV000147282, RCV000255026, RCV002513187, RCV003105777, RCV005031452" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023318...</a>
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<span class="mim-text-font">
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<p>For discussion of the arg37-to-ter (R37X) mutation in the PLA2G6 gene that was found in compound heterozygous state in a patient with infantile neuroaxonal dystrophy (NBIA2A; <a href="/entry/256600">256600</a>) by <a href="#16" class="mim-tip-reference" title="Tonelli, A., Romaniello, R., Grasso, R., Cavallini, A., Righini, A., Bresolin, N., Borgatti, R., Bassi, M. T. <strong>Novel splice-site mutations and a large intragenic deletion in PLA2G6 associated with a severe and rapidly progressive form of infantile neuroaxonal dystrophy.</strong> Clin. Genet. 78: 432-440, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20584031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20584031</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01417.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20584031">Tonelli et al. (2010)</a>, see <a href="#0014">603604.0014</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20584031" 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>.0016 PARKINSON DISEASE 14</strong>
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PLA2G6, ASP331TYR
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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> rs199935023 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199935023;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/rs199935023?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=rs199935023" 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=rs199935023" 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=RCV000023319 OR RCV000498427 OR RCV001852019 OR RCV002513188 OR RCV005025079" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023319, RCV000498427, RCV001852019, RCV002513188, RCV005025079" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023319...</a>
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<p>In a Chinese man, born of consanguineous parents, with early-onset Parkinson disease (PARK14; <a href="/entry/612953">612953</a>), <a href="#14" class="mim-tip-reference" title="Shi, C., Tang, B., Wang, L., Lv, Z., Wang, J., Luo, L., Shen, L., Jiang, H., Yan, X., Pan, Q., Xia, K., Guo, J. <strong>PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort.</strong> Neurology 77: 75-81, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21700586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21700586</a>] [<a href="https://doi.org/10.1212/WNL.0b013e318221acd3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21700586">Shi et al. (2011)</a> identified a homozygous 991G-T transversion in the PLA2G6 gene, resulting in an asp331-to-tyr (D331Y) substitution. The mutation was not found in 300 control individuals. The patient developed foot dragging and difficulty walking at age 37 years. Symptoms progressed to include masked facies, bradykinesia, and rigidity, but no atypical features. He had initial good response to L-DOPA treatment, but developed dyskinesias. Brain MRI excluded iron deposition. PET scan showed significant reduction in DAT binding in the basal ganglia. In vitro functional expression studies in HEK293 cells showed that the mutant PLA2G6 protein had about 30% residual activity. The patient's clinically unaffected 34-year-old sister was also homozygous for the mutation, and PET scan showed some loss of binding. The patient was identified in a cohort of 12 Chinese families with early-onset parkinsonism who were screened for PLA2G6 mutations; none of the other 11 families carried a PLA2G6 mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21700586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Bao2004" class="mim-anchor"></a>
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Bao, S., Miller, D. J., Ma, Z., Wohltmann, M., Eng, G., Ramanadham, S., Moley, K., Turk, J.
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<strong>Male mice that do not express group VIA phospholipase A(2) produce spermatozoa with impaired motility and have greatly reduced fertility.</strong>
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J. Biol. Chem. 279: 38194-38200, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15252026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15252026</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15252026[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=15252026" 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/10.1074/jbc.M406489200" target="_blank">Full Text</a>]
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Gregory, A., Polster, B. J., Hayflick, S. J.
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<strong>Clinical and genetic delineation of neurodegeneration with brain iron accumulation.</strong>
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J. Med. Genet. 46: 73-80, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18981035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18981035</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18981035[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=18981035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.2008.061929" target="_blank">Full Text</a>]
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Gregory2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gregory, A., Westaway, S. K., Holm, I. E., Kotzbauer, P. T., Hogarth, P., Sonek, S., Coryell, J. C., Nguyen, T. M., Nardocci, N., Zorzi, G., Rodriguez, D., Desguerre, I., and 10 others.
|
|
<strong>Neurodegeneration associated with genetic defects in phospholipase A(2).</strong>
|
|
Neurology 71: 1402-1409, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18799783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18799783</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18799783[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=18799783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000327094.67726.28" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Herbert2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Herbert, S. P., Walker, J. H.
|
|
<strong>Group VIA calcium-independent phospholipase A2 mediates endothelial cell S phase progression.</strong>
|
|
J. Biol. Chem. 281: 35709-35716, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16966332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16966332</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16966332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M600699200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Khateeb2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Khateeb, S., Flusser, H., Ofir, R., Shelef, I., Narkis, G., Vardi, G., Shorer, Z., Levy, R., Galil, A., Elbedour, K., Birk, O. S.
|
|
<strong>PLA2G6 mutation underlies infantile neuroaxonal dystrophy.</strong>
|
|
Am. J. Hum. Genet. 79: 942-948, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033970</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033970[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=17033970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/508572" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Larsson Forsell1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Larsson Forsell, P. K. A., Kennedy, B. P., Claesson, H.-E.
|
|
<strong>The human calcium-independent phospholipase A2 gene: multiple enzymes with distinct properties from a single gene.</strong>
|
|
Europ. J. Biochem. 262: 575-585, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10336645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10336645</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10336645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1432-1327.1999.00418.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Larsson1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Larsson, P. K. A., Claesson, H.-E., Kennedy, B. P.
|
|
<strong>Multiple splice variants of the human calcium-independent phospholipase A(2) and their effect on enzyme activity.</strong>
|
|
J. Biol. Chem. 273: 207-214, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9417066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9417066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9417066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.273.1.207" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Ma1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ma, Z., Wang, X., Nowatzke, W., Ramanadham, S., Turk, J.
|
|
<strong>Human pancreatic islets express mRNA species encoding two distinct catalytically active isoforms of group VI phospholipase A2 (iPLA2) that arise from an exon-skipping mechanism of alternative splicing of the transcript from the iPLA2 gene on chromosome 22q13.1.</strong>
|
|
J. Biol. Chem. 274: 9607-9616, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10092647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10092647</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10092647[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=10092647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.274.14.9607" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Magrinelli2022" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Magrinelli, F., Mehta, S., Di Lazzaro, G., Latorre, A., Edwards, M. J., Balint, B., Basu, P., Kobylecki, C., Groppa, S., Hegde, A., Mulroy, E., Estevez-Fraga, C., and 13 others.
|
|
<strong>Dissecting the phenotype of PLA2G6-related parkinsonism.</strong>
|
|
Mov. Disord. 37: 148-161, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34622992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34622992</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34622992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/mds.28807" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Malik2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Malik, I., Turk, J., Mancuso, D. J., Montier, L., Wohltmann, M., Wozniak, D. F., Schmidt, R. E., Gross, R. W., Kotzbauer, P. T.
|
|
<strong>Disrupted membrane homeostasis and accumulation of ubiquitinated proteins in a mouse model of infantile neuroaxonal dystrophy caused by PLA2G6 mutations.</strong>
|
|
Am. J. Path. 172: 406-416, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18202189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18202189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18202189[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=18202189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2353/ajpath.2008.070823" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Morgan2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morgan, N. V., Westaway, S. K., Morton, J. E. V., Gregory, A., Gissen, P., Sonek, S., Cangul, H., Coryell, J., Canham, N., Nardocci, N., Zorzi, G., Pasha, S., and 15 others.
|
|
<strong>PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.</strong>
|
|
Nature Genet. 38: 752-754, 2006. Note: Erratum: Nature Genet. 38: 957 only, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16783378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16783378</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16783378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng1826" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Paisan-Ruiz2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Paisan-Ruiz, C., Bhatia, K. P., Li, A., Hernandez, D., Davis, M., Wood, N. W., Hardy, J., Houlden, H., Singleton, A., Schneider, S. A.
|
|
<strong>Characterization of PLA2G6 as a locus for dystonia-parkinsonism.</strong>
|
|
Ann. Neurol. 65: 19-23, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18570303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18570303</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18570303[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=18570303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.21415" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Ramanadham2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ramanadham, S., Yarasheski, K. E., Silva, M. J., Wohltmann, M., Novack, D. V., Christiansen, B., Tu, X., Zhang, S., Lei, X., Turk, J.
|
|
<strong>Age-related changes in bone morphology are accelerated in group VIA phospholipase A2 (iPLA2-beta)-null mice.</strong>
|
|
Am. J. Path. 172: 868-881, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18349124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18349124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18349124[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=18349124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2353/ajpath.2008.070756" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Shi2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shi, C., Tang, B., Wang, L., Lv, Z., Wang, J., Luo, L., Shen, L., Jiang, H., Yan, X., Pan, Q., Xia, K., Guo, J.
|
|
<strong>PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort.</strong>
|
|
Neurology 77: 75-81, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21700586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21700586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21700586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/WNL.0b013e318221acd3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Tang1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tang, J., Kriz, R. W., Wolfman, N., Shaffer, M., Seehra, J., Jones, S. S.
|
|
<strong>A novel cytosolic calcium-independent phospholipase A(2) contains eight ankyrin motifs.</strong>
|
|
J. Biol. Chem. 272: 8567-8575, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9079687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9079687</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9079687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.272.13.8567" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Tonelli2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tonelli, A., Romaniello, R., Grasso, R., Cavallini, A., Righini, A., Bresolin, N., Borgatti, R., Bassi, M. T.
|
|
<strong>Novel splice-site mutations and a large intragenic deletion in PLA2G6 associated with a severe and rapidly progressive form of infantile neuroaxonal dystrophy.</strong>
|
|
Clin. Genet. 78: 432-440, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20584031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20584031</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20584031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2010.01417.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Turk2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Turk, J., Ramanadham, S.
|
|
<strong>The expression and function of a group VIA calcium-independent phospholipase A2 (iPLA2-beta) in beta-cells.</strong>
|
|
Canad. J. Physiol. Pharm. 82: 824-832, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15573142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15573142</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15573142" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1139/y04-064" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Yoshino2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yoshino, H., Tomiyama, H., Tachibana, N., Ogaki, K., Li, Y., Funayama, M., Hashimoto, T., Takashima, S., Hattori, N.
|
|
<strong>Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism.</strong>
|
|
Neurology 75: 1356-1361, 2010.
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20938027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20938027</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20938027" 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.0b013e3181f73649" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 05/12/2022
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/17/2011<br>Cassandra L. Kniffin - updated : 9/28/2011<br>Cassandra L. Kniffin - updated : 2/14/2011<br>Cassandra L. Kniffin - updated : 8/7/2009<br>Cassandra L. Kniffin - updated : 3/27/2009<br>Cassandra L. Kniffin - updated : 2/23/2009<br>Patricia A. Hartz - updated : 10/30/2008<br>Victor A. McKusick - updated : 10/10/2006<br>Victor A. McKusick - updated : 6/27/2006
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<a id="creationDate" class="mim-anchor"></a>
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Jennifer P. Macke : 3/3/1999
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/07/2022
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<span class="mim-text-font">
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carol : 10/06/2022<br>carol : 05/12/2022<br>carol : 07/19/2017<br>joanna : 08/28/2015<br>alopez : 8/3/2015<br>mcolton : 7/23/2015<br>mcolton : 2/24/2014<br>carol : 10/19/2011<br>ckniffin : 10/17/2011<br>carol : 10/12/2011<br>terry : 10/12/2011<br>ckniffin : 9/28/2011<br>wwang : 3/9/2011<br>ckniffin : 2/14/2011<br>ckniffin : 9/17/2010<br>carol : 3/1/2010<br>ckniffin : 2/18/2010<br>wwang : 8/28/2009<br>ckniffin : 8/7/2009<br>wwang : 4/14/2009<br>ckniffin : 3/27/2009<br>wwang : 2/25/2009<br>ckniffin : 2/23/2009<br>joanna : 12/3/2008<br>mgross : 11/5/2008<br>mgross : 11/3/2008<br>terry : 10/30/2008<br>ckniffin : 7/2/2008<br>wwang : 11/7/2007<br>ckniffin : 3/16/2007<br>alopez : 10/11/2006<br>terry : 10/10/2006<br>alopez : 6/28/2006<br>terry : 6/27/2006<br>alopez : 3/4/1999<br>alopez : 3/3/1999
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<span class="mim-font">
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<strong>*</strong> 603604
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<h3>
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<span class="mim-font">
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PHOSPHOLIPASE A2, GROUP VI; PLA2G6
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</h3>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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PHOSPHOLIPASE A2, CALCIUM-INDEPENDENT; IPLA2<br />
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PATATIN-LIKE PHOSPHOLIPASE DOMAIN-CONTAINING PROTEIN 9; PNPLA9<br />
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PHOSPHOLIPASE A2, CALCIUM-INDEPENDENT, GROUP VI, A<br />
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IPLA2-VIA
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</span>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: PLA2G6</em></strong>
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</span>
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</p>
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<strong>SNOMEDCT:</strong> 52713000;
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<strong>
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<em>
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Cytogenetic location: 22q13.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 22:38,111,495-38,181,830 </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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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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22q13.1
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<span class="mim-font">
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Infantile neuroaxonal dystrophy 1
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<span class="mim-font">
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256600
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<span class="mim-font">
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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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Neurodegeneration with brain iron accumulation 2B
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</td>
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<td>
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<span class="mim-font">
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610217
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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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<span class="mim-font">
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3
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<span class="mim-font">
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Parkinson disease 14, autosomal recessive
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<td>
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<span class="mim-font">
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612953
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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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</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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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Phospholipases A2 (PLA2s) catalyze hydrolysis of the sn-2 acyl-ester bonds in phospholipids, leading to the release of arachidonic acid and other fatty acids. PLA2G6 is a calcium-independent PLA2 (Larsson Forsell et al., 1999). </p>
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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>Tang et al. (1997) purified an 85-kD cytosolic calcium-independent PLA2, termed iPLA2, from Chinese hamster ovary (CHO) cells. They isolated a partial human cDNA from a Burkitt lymphoma cDNA library by screening with a CHO cDNA. Northern blot analysis revealed that iPLA2 is expressed in a variety of rodent tissues. </p><p>Larsson et al. (1998) cloned human iPLA2 cDNAs and discovered multiple mRNA isoforms resulting from alternative splicing. The full-length cDNA encodes an 806-amino acid protein with a lipase motif and 8 ankyrin repeats. Human and rodent iPLA2 share 90% overall amino acid sequence identity, with the human sequence differing in containing a 54-residue insertion that would interrupt the last putative ankyrin repeat. Two of the alternatively spliced forms encode only the ankyrin repeat region of the protein. Coexpression of these variants with the active iPLA2 enzyme resulted in a decrease of the enzyme's activity. </p><p>By computational analysis, Larsson Forsell et al. (1999) identified several human iPLA2 variants that were alternatively spliced at exons 3, 9, 9a, and 10a, as well as part of exon 14. Northern blot analysis detected iPLA2 transcripts of 1.8, 2.0, 3.2, and 4.2 kb. The 2.0-kb variant was expressed at variable levels in all tissues examined, the 3.2-kb and 4.2-kb transcripts were expressed at variable levels in most tissues examined, and the 1.8-kb transcript was expressed predominantly in heart and skeletal muscle, with lower levels in bone marrow. Western blot analysis of fractionated transfected COS-7 cells showed that full-length human iPLA2 associated with membranes. Hydropathy plot and bioinformatic analyses suggested that iPLA2 contains 2 hydrophobic regions that may be transmembrane domains. </p><p>Using rat iPla2 to screen a human insulinoma cDNA library, followed by RT-PCR of human islet RNA, Ma et al. (1999) cloned long and short iPLA2 splice variants. The short variant lacks an insert encoding a 54-amino acid proline-rich region in the long variant. This insert interrupts the last putative ankyrin repeat and is likely to function as a linker region that separates the N-terminal protein-binding domain from the C-terminal catalytic domain. RT-PCR detected these 2 transcripts in a human promonocytic cell line and in normal islet cells. SDS-PAGE showed that the recombinant short and long isoforms of human iPLA2 had apparent molecular masses of 85 kD and 88 kD, respectively. </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>Larsson Forsell et al. (1999) determined that the PLA2G6 gene contains 19 exons, including the alternative exons 9a and 10a, and spans more than 69 kb. The promoter region lacks a TATA box, but contains a CpG island and several potential SP1 (189906)-binding sites. The 5-prime flanking region also contains an inverted MER53 sequence and an Alu element. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ma et al. (1999) mapped the PLA2G6 gene to chromosome 22q13.1 by FISH. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Tang et al. (1997) found that expression of the hamster iPla2 cDNA generated an active 85-kD protein that selectively hydrolyzed sn-2 over sn-1 fatty acids. </p><p>Larsson Forsell et al. (1999) found that COS-7 cells expressing full-length human iPLA2 and rat vascular smooth muscle cells showed Ca(2+)-independent release of arachidonic acid from radiolabeled phospholipids, and that the activity was associated with the membrane fractions. </p><p>Ma et al. (1999) found that both recombinant short and long isoforms of human iPLA2 had Ca(2+)-independent PLA2 activity in cytosolic and membrane fractions. Their activities were inhibited by bromoenol lactone, an iPLA2 suicide substrate. The long iPLA2 isoform, but not the short isoform, was activated by ATP. </p><p>Turk and Ramanadham (2004) stated that the shorter iPLA2 isoforms that lack the C-terminal catalytic domain function as negative modulators of iPLA2-beta, the full-length isoform. They also noted that iPLA2-beta can be proteolytically processed to yield truncated products that are constitutively active. Turk and Ramanadham (2004) reviewed the role of iPLA2 in phospholipid remodeling, signal transduction, cell proliferation, and endoplasmic reticulum stress-mediated apoptosis. They stated that, in pancreatic islets, beta cells, and insulinoma cells, iPLA2-beta participates in glucose-stimulated insulin secretion, but it is not involved in membrane phospholipid remodeling. </p><p>Arachidonic acid and its metabolites are involved in regulation of endothelial cell proliferation. Herbert and Walker (2006) showed that bromoenol lactone-mediated inhibition of iPLA2-VIA activity in human endothelial cells blocked endothelial cell growth and inhibited DNA synthesis in a dose-dependent manner. These effects were reversed upon the exogenous addition of arachidonic acid. iPLA2-VIA activity was required for expression of the cyclin A (see CCNA1; 604036)/CDK2 (116953) complex, and thus inhibition of iPLA2-VIA blocked S phase progression and resulted in exit from the cell cycle. Inhibition of iPLA2-VIA-mediated endothelial cell proliferation was sufficient to block angiogenic tubule formation by human endothelial cells cocultured with human dermal fibroblasts. Herbert and Walker (2006) concluded that, by generating arachidonic acid, iPLA2-VIA regulates endothelial cell S phase progression, cell cycle residence, and angiogenesis. They noted that iPLA2-VIA is involved in cell growth and division in other cell types through arachidonic acid-independent regulation of glycerophospholipid metabolism during the cell cycle. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Neurodegeneration with Brain Iron Accumulation 2A and 2B and Karak Syndrome</em></strong></p><p>
|
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In studies of 12 families with infantile neuroaxonal dystrophy (INAD, NBIA2A; 256600) and a large consanguineous Pakistani family with neurodegeneration with brain iron accumulation (NBIA2B; 610217), Morgan et al. (2006) mapped a novel INAD locus to 22q12.3-q13.2 (lod score 4.78), with evidence of locus heterogeneity. They also detected linkage to 22q12-q13 in a family with NBIA (lod score 4.65) suggesting allelism. After sequencing 70 of the approximately 100 positional candidate genes, they detected mutations in PLA2G6 in 4 kindreds, including the Pakistani family with NBIA2B and 3 INAD probands (603604.0001-603604.0005). They also identified PLA2G6 mutations in 28 additional probands with INAD and in the original family with Karak syndrome and high basal ganglia iron (see 610217). In all, they identified 44 unique mutations (32 missense, 5 deletions leading to frameshift, 3 nonsense, 2 leading to amino acid deletions without frameshift, 1 splice site, and 1 large deletion). Of the missense mutations, 85% occurred at amino acid positions that are conserved in vertebrates. </p><p>In an independent study, Khateeb et al. (2006) identified a homozygous mutation in PLA2G6 in 2 consanguineous Israeli Bedouin kindreds with infantile neuroaxonal dystrophy (NBIA2A). The 3-bp deletion (603604.0004) resulted in the deletion of valine-691. </p><p>Gregory et al. (2008) found PLA2G6 mutations in 45 (79%) of 56 patients with INAD1 (NBIA2A) and in 6 (20%) of 23 patients with idiopathic NBIA2B (see, e.g., 603604.0006-603604.0008). No PLA2G6 mutations were found in 11 patients with clinical evidence of INAD, including 5 in whom spheroids were reported on peripheral nerve biopsy. All 28 patients with 2 null mutations or homozygous for any mutation had early onset and rapidly progressive disease. Patients with the less severe phenotype of NBIA tended to have compound heterozygous missense mutations, consistent with residual protein function. </p><p><strong><em>Parkinson Disease 14</em></strong></p><p>
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In 2 unrelated families with adult-onset dystonia-parkinsonism (PARK14; 612953), Paisan-Ruiz et al. (2009) identified 2 different homozygous mutations in the PLA2G6 gene (R741Q; 603604.0009 and R747W; 603604.0010, respectively). The disorder was characterized by rapidly progressive cognitive decline, bradykinesia, rigidity, and dystonia. None of the 3 affected patients had evidence of brain iron accumulation. The authors emphasized that PLA2G6 mutations should be considered in patients with neurodegeneration even without brain iron on MRI scan. </p><p>Magrinelli et al. (2022) reported 14 new patients from 12 families with PARK14 and performed a systematic search for patients with PARK14 in the literature, identifying a total of 86 patients from 68 families, including their own. Parental consanguinity was seen in 55% of families. Homozygosity for mutations in the PLA2G6 gene was seen in 46/86 (53.5%), with compound heterozygosity in 40/86 (46.5%). A total of 54 mutations in PLA2G6 have been associated with parkinsonism, including 4 novel variants in the newly reported patients. Among the 54 mutations, 44 were missense, 2 were in-frame deletions, 4 were splicing, 2 were nonsense, and 2 were frameshift mutations. The most commonly observed mutations were D331Y (603604.0016), seen in 17 families, mainly from China and Taiwan, and R741Q (603604.0009), seen in 12 families from India, Pakistan, and Saudi Arabia. </p>
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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>Genotype/Phenotype Correlations</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>In a systematic review of 86 patients from 68 families with PARK14, Magrinelli et al. (2022) found that most mutations were nontruncating, which might be less detrimental to protein function than the truncating mutations involved with infantile neuroaxonal dystrophy. Based on limited biochemical and enzymatic studies, the authors suggested that mutations associated with NBIA2A and NBIA2B result in loss of enzyme activity, whereas those associated with PARK14 do not impair phospholipase or lysophospholipase catalytic activity. </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>Bao et al. (2004) obtained Ipla2-beta-null mice at a mendelian ratio. They found that spermatozoa from Ipla2-beta -/- mice had reduced motility and impaired ability to fertilize mouse oocytes in vitro and in vivo. Female Ipla2-beta -/- mice had nearly normal fertility. </p><p>Ramanadham et al. (2008) found that Ipla2-beta-null mice had cortical bone size, trabecular bone volume, bone mineralizing surfaces, and bone strength similar to wildtype mice at 3 months of age. Both groups showed declines in these measures with age, but the decline was more pronounced in Ipla2-beta-null mice. The lower bone mass in Ipla2-beta-null mice was accompanied by an increase in bone marrow fat. Relative to wildtype mice, undifferentiated bone marrow stromal cells from knockout mice expressed higher levels of Pparg (601487) and lower levels of Runx2 (600211) mRNA, and these changes correlated with increased adipogenesis and decreased osteogenesis in bone marrow stromal cells in knockout mice. </p><p>Malik et al. (2008) found that Pla2g6-null mice developed age-dependent neurologic impairment that was evident in rotarod, balance, and climbing tests by 13 months of age. Neuropathologic analysis showed numerous spheroids in the brain similar to those observed in human INAD. Spheroids contained tubulovesicular membranes and stained strongly with anti-ubiquitin antibodies. Onset of motor impairment correlated with increased spheroids throughout the neuropil in nearly all brain 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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<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 2A</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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PLA2G6, TYR790TER
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<br />
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SNP: rs121908680,
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gnomAD: rs121908680,
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ClinVar: RCV000006572, RCV000147321, RCV000323935, RCV000623021, RCV000763481, RCV000778661, RCV001250474, RCV001333134, RCV001813959, RCV002265549, RCV003407288
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a proband with classic infantile neuroaxonal dystrophy (NBIA2A; 256600), Morgan et al. (2006) identified a 2370T-G transversion in exon 17 of the PLA2G6 gene that was predicted to result in a premature termination in the protein (tyr790 to stop; Y790X). The parents were known to be consanguineous and the mutation was present in homozygous state. The presence of spheroids had been demonstrated. </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 2B</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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PLA2G6, LYS545THR
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<br />
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SNP: rs121908681,
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gnomAD: rs121908681,
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ClinVar: RCV000006573, RCV001003639, RCV001542712, RCV003319301
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a large consanguineous Pakistani family with neurodegeneration with brain iron accumulation-2B (NBIA2B; 610217), Morgan et al. (2006) identified homozygosity for a missense mutation in exon 12 of the PLA2G6 gene, a 1634A-C transversion that resulted in a lys545-to-thr substitution (K545T). </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 2A</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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PLA2G6, VAL310GLU
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<br />
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SNP: rs121908682,
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gnomAD: rs121908682,
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ClinVar: RCV000006574, RCV002512835
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a case of classic infantile neuroaxonal dystrophy (NBIA2A; 256600), Morgan et al. (2006) described a 929T-A transversion in exon 7 of the PLA2G6 gene, predicted to result in a val310-to-glu (V310E) amino acid change in the protein. The mutation was present in homozygous state. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0004 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</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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PLA2G6, 3-BP DEL, 2070TGT
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<br />
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SNP: rs587784343,
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ClinVar: RCV000006575, RCV000147311, RCV000480455, RCV000761526, RCV001523781
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a case of classic infantile neuroaxonal dystrophy (NBIA2A; 256600), Morgan et al. (2006) found a 3-bp deletion in exon 15 of the PLA2G6 gene, 2070_2072delTGT, resulting in deletion of val691 from the protein (V691del). The mutation was present in homozygous state, or possibly hemizygous state because of deletion of 1 allele. </p><p>In a consanguineous Bedouin kindred with cases of infantile neuroaxonal dystrophy in 3 separate sibships and in another kindred with a single affected individual, Khateeb et al. (2006) found the same 3-nucleotide deletion. The mutation was also found in heterozygosity in a single individual among 300 unrelated Bedouin controls. Both affected families and the unrelated carrier had the same haplotype surrounding the mutation. </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 KARAK SYNDROME</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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|
PLA2G6, ARG632TRP
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|
<br />
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|
|
SNP: rs121908683,
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|
|
gnomAD: rs121908683,
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|
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|
|
ClinVar: RCV000006576, RCV001092011, RCV001582469, RCV002512836, RCV003507245, RCV005031400
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|
|
|
|
|
</span>
|
|
</div>
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the original family with Karak syndrome (see 610217), Morgan et al. (2006) detected homozygosity for a C-to-T transition at nucleotide 1894 in exon 14 of the PLA2G6 gene that resulted in a substitution of trp for arg at codon 632 (R632W). </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>.0006 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
PLA2G6, TYR790TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908680,
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|
|
|
|
|
gnomAD: rs121908680,
|
|
|
|
|
|
ClinVar: RCV000006572, RCV000147321, RCV000323935, RCV000623021, RCV000763481, RCV000778661, RCV001250474, RCV001333134, RCV001813959, RCV002265549, RCV003407288
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|
|
|
|
</span>
|
|
</div>
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|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 patients with infantile neuroaxonal dystrophy (NBIA2A; 256600), Gregory et al. (2008) identified a homozygous 2370T-G transversion in the PLA2G6 gene, resulting in a tyr790-to-ter (Y790X) substitution. The INAD1 phenotype was characterized by early onset of psychomotor regression with truncal hypotonia and rapid progression to tetraparesis. </p>
|
|
</span>
|
|
</div>
|
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<div>
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|
<br />
|
|
</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 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2B, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PLA2G6, 2-BP DEL, 2370TG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587784353,
|
|
|
|
|
|
gnomAD: rs587784353,
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|
|
|
|
|
ClinVar: RCV000006578, RCV000006579, RCV000147322, RCV000255768, RCV002504755, RCV002512837, RCV002512838
|
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|
|
|
</span>
|
|
</div>
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Neurodegeneration with Brain Iron Accumulation 2A</em></strong></p><p>
|
|
In a patient with infantile neuroaxonal dystrophy (NBIA2A; 256600), Gregory et al. (2008) identified a homozygous 2-bp deletion (2370delTG) in the PLA2G6 gene, which resulted in premature termination at codon 790 similar to the Y790X mutation (603604.0006). </p><p><strong><em>Neurodegeneration with Brain Iron Accumulation 2B</em></strong></p><p>
|
|
In a patient with neurodegeneration with brain iron accumulation-2B (NBIA2B; 610217), Gregory et al. (2008) identified compound heterozygosity for the 2370delTG mutation and a 238G-A transition, resulting in an ala80-to-thr (A80T; 603604.0007) substitution. The patient presented at 3 years of age with toe walking and lower extremity spasticity. She developed optic atrophy and became nonambulatory by 5 years of age with dystonia and dysarthria, progressing to profound sensorimotor impairment by age 9 years. She died at age 23 years. Postmortem examination showed neuronal loss, axonal swelling, and Lewy bodies and neurofibrillary tangles. </p>
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</span>
|
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</div>
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<div>
|
|
<br />
|
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</div>
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|
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</div>
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<div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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PLA2G6, ALA80THR
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<br />
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|
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SNP: rs121908685,
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gnomAD: rs121908685,
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ClinVar: RCV000006580, RCV000535771, RCV000660638, RCV001540404, RCV002512839
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of the ala80-to-thr (A80T) mutation in the PLA2G6 gene that was found in compound heterozygous state in a patient with neurodegeneration with brain iron accumulation-2B (NBIA2B; 610217) by Gregory et al. (2008), see 603604.0007. </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>.0009 PARKINSON DISEASE 14</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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PLA2G6, ARG741GLN
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<br />
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|
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SNP: rs121908686,
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gnomAD: rs121908686,
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ClinVar: RCV000006581, RCV000811054, RCV001251187, RCV001588801, RCV002496284, RCV003155018
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 2 affected first cousins from a large consanguineous Indian kindred segregating adult-onset dystonia-parkinsonism (PARK14; 612953), Paisan-Ruiz et al. (2009) identified a homozygous 2222G-A transition in the PLA2G6 gene, resulting in an arg741-to-gln (R741Q) substitution in a conserved residue. Both had onset at age 26 years of a rapidly progressive neurodegenerative disorder characterized by rapid cognitive decline, bradykinesia, tremor and imbalance, eventually leading to loss of mobility. Although Paisan-Ruiz et al. (2009) noted that brain MRI showed no evidence of brain iron accumulation, Gregory et al. (2009) stated that this disorder could be considered under the umbrella designation of atypical neurodegeneration with brain iron accumulation (NBIA). </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>.0010 PARKINSON DISEASE 14</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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PLA2G6, ARG747TRP
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<br />
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|
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SNP: rs121908687,
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gnomAD: rs121908687,
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ClinVar: RCV000006582, RCV000763482, RCV001268312, RCV002512840, RCV003507246
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Pakistani man, born of consanguineous parents, with adult-onset dystonia-parkinsonism (PARK14; 612953), Paisan-Ruiz et al. (2009) identified a homozygous 2239C-T transition in the PLA2G6 gene, resulting in an arg747-to-trp (R747W) substitution in a conserved region. The patient had onset at age 18 years of rapid cognitive decline with personality changes, foot dystonia, parkinsonism, and spasticity. Although Paisan-Ruiz et al. (2009) noted that brain MRI showed no evidence of brain iron accumulation, Gregory et al. (2009) stated that this disorder could be considered under the umbrella designation of atypical neurodegeneration with brain iron accumulation (NBIA). </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0011 PARKINSON DISEASE 14</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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PLA2G6, ARG635GLN
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<br />
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SNP: rs387906863,
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gnomAD: rs387906863,
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ClinVar: RCV000023314, RCV000779372, RCV002273936, RCV002477008, RCV002513186
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 3 Japanese patients, including 2 sibs, with early-onset Parkinson disease-14 (PARK14; 612953), Yoshino et al. (2010) identified compound heterozygosity for 2 mutations in the PLA2G6 gene. All 3 patients carried a 1904G-A transition, resulting in an arg635-to-gln (R635Q) substitution in the catalytic domain. The 2 sibs also had a heterozygous 1354C-T transition, resulting in a gln452-to-ter (Q452X; 603604.0012) substitution, and the third unrelated patient had a heterozygous 216C-A transversion, resulting in a phe72-to-leu (F72L; 603604.0013) substitution. Haplotype analysis suggested a founder effect for the R635Q mutation. All 3 patients had onset before age 30 years of L-DOPA-responsive parkinsonism with varying degrees of cognitive decline and frontotemporal lobar atrophy. Brain MRI of 1 patient showed iron accumulation in the substantia nigra and striatum. None of the parents with heterozygous mutations had signs of the disorder. </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>.0012 PARKINSON DISEASE 14</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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PLA2G6, GLN452TER
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<br />
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SNP: rs387906864,
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gnomAD: rs387906864,
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ClinVar: RCV000023315
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of the gln452-to-ter (Q452X) mutation in the PLA2G6 gene that was found in compound heterozygous state in 2 sibs with early-onset Parkinson disease-14 (PARK14; 612953) by Yoshino et al. (2010), see 603604.0011. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</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>.0013 PARKINSON DISEASE 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
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PLA2G6, PHE72LEU
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<br />
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SNP: rs774631197,
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|
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|
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gnomAD: rs774631197,
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|
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|
|
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ClinVar: RCV000023316
|
|
|
|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the phe72-to-leu (F72L) mutation in the PLA2G6 gene that was found in compound heterozygous state in a patient with early-onset Parkinson disease-14 (PARK14; 612953) by Yoshino et al. (2010), see 603604.0011. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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PLA2G6, 6.6-KB DEL
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<br />
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ClinVar: RCV000023317
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|
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</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with infantile neuroaxonal dystrophy (NBIA2A; 256600), Tonelli et al. (2010) identified compound heterozygosity for 2 mutations in the PLA2G6 gene: a 6.6-kb deletion from intron 4 to 6, resulting in an in-frame deletion and removal of exons 5 and 6 and a large portion of the ankyrin repeats motif, and a 109C-T transition in exon 2 resulting in an arg37-to-ter (R37X; 603604.0015) substitution. Analysis of the deletion junction in the first mutation showed that both breakpoints occurred within AluY sequences, suggesting that the deletion was likely mediated by nonallelic homologous recombination (NAHR). The mutations were predicted to result in an almost complete lack of enzyme activity, although a gain of function could not be excluded. The patient had a severe and rapidly progressive disease course, with onset before age 12 months, hypotonia, severe developmental delay with mental retardation, and no eye contact. Spastic tetraparesis developed by age 18 months. Skin biopsy showed axonal spheroids. Although brain iron accumulation was not present, MRI at age 20 months showed hyperintensities on T2-weighted imaging in the caudate and putamen, suggesting an early degeneration process. Brain MRI at age 3 years showed cerebellar cortical atrophy. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
PLA2G6, ARG37TER
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<br />
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|
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SNP: rs200075782,
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|
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|
|
|
gnomAD: rs200075782,
|
|
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|
|
|
ClinVar: RCV000023318, RCV000147282, RCV000255026, RCV002513187, RCV003105777, RCV005031452
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg37-to-ter (R37X) mutation in the PLA2G6 gene that was found in compound heterozygous state in a patient with infantile neuroaxonal dystrophy (NBIA2A; 256600) by Tonelli et al. (2010), see 603604.0014. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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<div>
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 PARKINSON DISEASE 14</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
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|
|
PLA2G6, ASP331TYR
|
|
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|
|
<br />
|
|
|
|
SNP: rs199935023,
|
|
|
|
|
|
gnomAD: rs199935023,
|
|
|
|
|
|
ClinVar: RCV000023319, RCV000498427, RCV001852019, RCV002513188, RCV005025079
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Chinese man, born of consanguineous parents, with early-onset Parkinson disease (PARK14; 612953), Shi et al. (2011) identified a homozygous 991G-T transversion in the PLA2G6 gene, resulting in an asp331-to-tyr (D331Y) substitution. The mutation was not found in 300 control individuals. The patient developed foot dragging and difficulty walking at age 37 years. Symptoms progressed to include masked facies, bradykinesia, and rigidity, but no atypical features. He had initial good response to L-DOPA treatment, but developed dyskinesias. Brain MRI excluded iron deposition. PET scan showed significant reduction in DAT binding in the basal ganglia. In vitro functional expression studies in HEK293 cells showed that the mutant PLA2G6 protein had about 30% residual activity. The patient's clinically unaffected 34-year-old sister was also homozygous for the mutation, and PET scan showed some loss of binding. The patient was identified in a cohort of 12 Chinese families with early-onset parkinsonism who were screened for PLA2G6 mutations; none of the other 11 families carried a PLA2G6 mutation. </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">
|
|
Bao, S., Miller, D. J., Ma, Z., Wohltmann, M., Eng, G., Ramanadham, S., Moley, K., Turk, J.
|
|
<strong>Male mice that do not express group VIA phospholipase A(2) produce spermatozoa with impaired motility and have greatly reduced fertility.</strong>
|
|
J. Biol. Chem. 279: 38194-38200, 2004.
|
|
|
|
|
|
[PubMed: 15252026]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M406489200]
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</p>
|
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</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Gregory, A., Polster, B. J., Hayflick, S. J.
|
|
<strong>Clinical and genetic delineation of neurodegeneration with brain iron accumulation.</strong>
|
|
J. Med. Genet. 46: 73-80, 2009.
|
|
|
|
|
|
[PubMed: 18981035]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2008.061929]
|
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</p>
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</li>
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|
|
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<li>
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<p class="mim-text-font">
|
|
Gregory, A., Westaway, S. K., Holm, I. E., Kotzbauer, P. T., Hogarth, P., Sonek, S., Coryell, J. C., Nguyen, T. M., Nardocci, N., Zorzi, G., Rodriguez, D., Desguerre, I., and 10 others.
|
|
<strong>Neurodegeneration associated with genetic defects in phospholipase A(2).</strong>
|
|
Neurology 71: 1402-1409, 2008.
|
|
|
|
|
|
[PubMed: 18799783]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000327094.67726.28]
|
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Herbert, S. P., Walker, J. H.
|
|
<strong>Group VIA calcium-independent phospholipase A2 mediates endothelial cell S phase progression.</strong>
|
|
J. Biol. Chem. 281: 35709-35716, 2006.
|
|
|
|
|
|
[PubMed: 16966332]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M600699200]
|
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</p>
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</li>
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|
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<li>
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<p class="mim-text-font">
|
|
Khateeb, S., Flusser, H., Ofir, R., Shelef, I., Narkis, G., Vardi, G., Shorer, Z., Levy, R., Galil, A., Elbedour, K., Birk, O. S.
|
|
<strong>PLA2G6 mutation underlies infantile neuroaxonal dystrophy.</strong>
|
|
Am. J. Hum. Genet. 79: 942-948, 2006.
|
|
|
|
|
|
[PubMed: 17033970]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/508572]
|
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|
|
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Larsson Forsell, P. K. A., Kennedy, B. P., Claesson, H.-E.
|
|
<strong>The human calcium-independent phospholipase A2 gene: multiple enzymes with distinct properties from a single gene.</strong>
|
|
Europ. J. Biochem. 262: 575-585, 1999.
|
|
|
|
|
|
[PubMed: 10336645]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1432-1327.1999.00418.x]
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Larsson, P. K. A., Claesson, H.-E., Kennedy, B. P.
|
|
<strong>Multiple splice variants of the human calcium-independent phospholipase A(2) and their effect on enzyme activity.</strong>
|
|
J. Biol. Chem. 273: 207-214, 1998.
|
|
|
|
|
|
[PubMed: 9417066]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.273.1.207]
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</p>
|
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</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Ma, Z., Wang, X., Nowatzke, W., Ramanadham, S., Turk, J.
|
|
<strong>Human pancreatic islets express mRNA species encoding two distinct catalytically active isoforms of group VI phospholipase A2 (iPLA2) that arise from an exon-skipping mechanism of alternative splicing of the transcript from the iPLA2 gene on chromosome 22q13.1.</strong>
|
|
J. Biol. Chem. 274: 9607-9616, 1999.
|
|
|
|
|
|
[PubMed: 10092647]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.274.14.9607]
|
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</p>
|
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</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Magrinelli, F., Mehta, S., Di Lazzaro, G., Latorre, A., Edwards, M. J., Balint, B., Basu, P., Kobylecki, C., Groppa, S., Hegde, A., Mulroy, E., Estevez-Fraga, C., and 13 others.
|
|
<strong>Dissecting the phenotype of PLA2G6-related parkinsonism.</strong>
|
|
Mov. Disord. 37: 148-161, 2022.
|
|
|
|
|
|
[PubMed: 34622992]
|
|
|
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|
|
[Full Text: https://doi.org/10.1002/mds.28807]
|
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Malik, I., Turk, J., Mancuso, D. J., Montier, L., Wohltmann, M., Wozniak, D. F., Schmidt, R. E., Gross, R. W., Kotzbauer, P. T.
|
|
<strong>Disrupted membrane homeostasis and accumulation of ubiquitinated proteins in a mouse model of infantile neuroaxonal dystrophy caused by PLA2G6 mutations.</strong>
|
|
Am. J. Path. 172: 406-416, 2008.
|
|
|
|
|
|
[PubMed: 18202189]
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|
|
[Full Text: https://doi.org/10.2353/ajpath.2008.070823]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Morgan, N. V., Westaway, S. K., Morton, J. E. V., Gregory, A., Gissen, P., Sonek, S., Cangul, H., Coryell, J., Canham, N., Nardocci, N., Zorzi, G., Pasha, S., and 15 others.
|
|
<strong>PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.</strong>
|
|
Nature Genet. 38: 752-754, 2006. Note: Erratum: Nature Genet. 38: 957 only, 2006.
|
|
|
|
|
|
[PubMed: 16783378]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1826]
|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Paisan-Ruiz, C., Bhatia, K. P., Li, A., Hernandez, D., Davis, M., Wood, N. W., Hardy, J., Houlden, H., Singleton, A., Schneider, S. A.
|
|
<strong>Characterization of PLA2G6 as a locus for dystonia-parkinsonism.</strong>
|
|
Ann. Neurol. 65: 19-23, 2009.
|
|
|
|
|
|
[PubMed: 18570303]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.21415]
|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ramanadham, S., Yarasheski, K. E., Silva, M. J., Wohltmann, M., Novack, D. V., Christiansen, B., Tu, X., Zhang, S., Lei, X., Turk, J.
|
|
<strong>Age-related changes in bone morphology are accelerated in group VIA phospholipase A2 (iPLA2-beta)-null mice.</strong>
|
|
Am. J. Path. 172: 868-881, 2008.
|
|
|
|
|
|
[PubMed: 18349124]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2353/ajpath.2008.070756]
|
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|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Shi, C., Tang, B., Wang, L., Lv, Z., Wang, J., Luo, L., Shen, L., Jiang, H., Yan, X., Pan, Q., Xia, K., Guo, J.
|
|
<strong>PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort.</strong>
|
|
Neurology 77: 75-81, 2011.
|
|
|
|
|
|
[PubMed: 21700586]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e318221acd3]
|
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Tang, J., Kriz, R. W., Wolfman, N., Shaffer, M., Seehra, J., Jones, S. S.
|
|
<strong>A novel cytosolic calcium-independent phospholipase A(2) contains eight ankyrin motifs.</strong>
|
|
J. Biol. Chem. 272: 8567-8575, 1997.
|
|
|
|
|
|
[PubMed: 9079687]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.272.13.8567]
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|
|
</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Tonelli, A., Romaniello, R., Grasso, R., Cavallini, A., Righini, A., Bresolin, N., Borgatti, R., Bassi, M. T.
|
|
<strong>Novel splice-site mutations and a large intragenic deletion in PLA2G6 associated with a severe and rapidly progressive form of infantile neuroaxonal dystrophy.</strong>
|
|
Clin. Genet. 78: 432-440, 2010.
|
|
|
|
|
|
[PubMed: 20584031]
|
|
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[Full Text: https://doi.org/10.1111/j.1399-0004.2010.01417.x]
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Turk, J., Ramanadham, S.
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<strong>The expression and function of a group VIA calcium-independent phospholipase A2 (iPLA2-beta) in beta-cells.</strong>
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Canad. J. Physiol. Pharm. 82: 824-832, 2004.
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[PubMed: 15573142]
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[Full Text: https://doi.org/10.1139/y04-064]
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Yoshino, H., Tomiyama, H., Tachibana, N., Ogaki, K., Li, Y., Funayama, M., Hashimoto, T., Takashima, S., Hattori, N.
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<strong>Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism.</strong>
|
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Neurology 75: 1356-1361, 2010.
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[PubMed: 20938027]
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[Full Text: https://doi.org/10.1212/WNL.0b013e3181f73649]
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Sonja A. Rasmussen - updated : 05/12/2022<br>Cassandra L. Kniffin - updated : 10/17/2011<br>Cassandra L. Kniffin - updated : 9/28/2011<br>Cassandra L. Kniffin - updated : 2/14/2011<br>Cassandra L. Kniffin - updated : 8/7/2009<br>Cassandra L. Kniffin - updated : 3/27/2009<br>Cassandra L. Kniffin - updated : 2/23/2009<br>Patricia A. Hartz - updated : 10/30/2008<br>Victor A. McKusick - updated : 10/10/2006<br>Victor A. McKusick - updated : 6/27/2006
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