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Entry
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- *606463 - GLUCOSIDASE, BETA, ACID; GBA
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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">*606463</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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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<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="#populationGenetics">Population Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606463">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<div id="mimFloatingLinksMenu">
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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=ENSG00000177628;t=ENST00000368373" 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=2629" 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=606463" 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=ENSG00000177628;t=ENST00000368373" 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_000157,NM_001005741,NM_001005742,NM_001171811,NM_001171812" 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_000157" 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=606463" 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=06973&isoform_id=06973_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/GBA1" 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/183008,183012,183017,183018,183022,183024,183026,183028,496369,553300,2564914,13097171,54607043,54607045,54607047,55584151,119573485,119573486,119573487,119573488,158257254,189065565,221042442,221043110,221043360,221043376,221043580,221043794,221043856,284807150,284807152,658508440,658508445,658508452,1233272219,2259607772,2259607774,2259607776" 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/P04062" 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=2629" 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=ENSG00000177628;t=ENST00000368373" 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=GBA1" 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=GBA1" 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+2629" 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/GBA1" 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:2629" 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/2629" 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=chr1&hgg_gene=ENST00000368373.8&hgg_start=155234452&hgg_end=155244627&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:4177" 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:4177" 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/gba1" 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=606463[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=606463[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/GBA1/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/ENSG00000177628" 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=GBA1" 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=GBA1" 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=GBA1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://research.cchmc.org/LOVD2/home.php?select_db=GBA" 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=GBA1&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/PA28591" 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:4177" 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/FBgn0051148.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:95665" 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/GBA1#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:95665" 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/2629/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/OMIA002621/" 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=2629" 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=WBGene00008706;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00008706 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00021160;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00021160 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-100922-270" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:606463" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2629" 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=GBA1&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> 12246008, 5963005, 62201009, 870313002<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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606463
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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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GLUCOSIDASE, BETA, ACID; GBA
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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>
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<h4>
|
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<span class="mim-font">
|
|
GBA1<br />
|
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ACID BETA-GLUCOSIDASE<br />
|
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BETA-GLUCOSIDASE, ACID<br />
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BETA-GC<br />
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GLUCOCEREBROSIDASE<br />
|
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GLUCOSYLCERAMIDASE
|
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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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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
|
Other entities represented in this entry:
|
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</span>
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</p>
|
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</div>
|
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<div>
|
|
<span class="h3 mim-font">
|
|
GLUCOCEREBROSIDASE PSEUDOGENE, INCLUDED; GBAP, INCLUDED
|
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</span>
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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=GBA1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GBA1</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/1/1217?start=-3&limit=10&highlight=1217">1q22</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:155234452-155244627&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'})">1:155,234,452-155,244,627</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
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<a href="/clinicalSynopsis/table?mimNumber=127750,168600,608013,230800,230900,231000,231005" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
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View Clinical Synopses
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</a>
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="7">
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<span class="mim-font">
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<a href="/geneMap/1/1217?start=-3&limit=10&highlight=1217">
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1q22
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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{Lewy body dementia, susceptibility to}
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/127750"> 127750 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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{Parkinson disease, late-onset, susceptibility to}
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/168600"> 168600 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Multifactorial">Mu</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Gaucher disease, perinatal lethal
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/608013"> 608013 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Gaucher disease, type I
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/230800"> 230800 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Gaucher disease, type II
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/230900"> 230900 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
|
Gaucher disease, type III
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/231000"> 231000 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Gaucher disease, type IIIC
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
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|
|
<a href="/entry/231005"> 231005 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
|
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/606463" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/606463" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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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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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Acid beta-glucocerebrosidase, also known as beta-glucosidase (GBA; <a href="https://enzyme.expasy.org/EC/3.2.1.45" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 3.2.1.45</a>), is a lysosomal enzyme that catalyzes the breakdown of the glycolipid glucosylceramide (GlcCer) to ceramide and glucose (<a href="#13" class="mim-tip-reference" title="Beutler, E. <strong>Gaucher disease: new molecular approaches to diagnosis and treatment.</strong> Science 256: 794-799, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1589760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1589760</a>] [<a href="https://doi.org/10.1126/science.1589760" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1589760">Beutler, 1992</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1589760" 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>
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<div>
|
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<br />
|
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</div>
|
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</div>
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|
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<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
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<strong>Cloning and Expression</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div id="mimCloningFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
|
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<p><a href="#98" class="mim-tip-reference" title="Sorge, J., West, C., Westwood, B., Beutler, E. <strong>Molecular cloning and nucleotide sequence of human glucocerebrosidase cDNA.</strong> Proc. Nat. Acad. Sci. 82: 7289-7293, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3864160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3864160</a>] [<a href="https://doi.org/10.1073/pnas.82.21.7289" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3864160">Sorge et al. (1985)</a> isolated and characterized a cDNA clone corresponding to the human beta-glucosidase gene from a human cDNA library. Using the ATG at positions 154-156 as the correct initiator codon, the deduced protein is 515 amino acids long and contains a 19-amino acid signal sequence. The mature 496-residue protein has a calculated molecular mass of 55.4 kD. The cDNA directed the synthesis of functional glucocerebrosidase when expressed in mammalian cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3864160" 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="#111" class="mim-tip-reference" title="Tsuji, S., Choudary, P. V., Martin, B. M., Winfield, S., Barranger, J. A., Ginns, E. I. <strong>Nucleotide sequence of cDNA containing the complete coding sequence for human lysosomal glucocerebrosidase.</strong> J. Biol. Chem. 261: 50-53, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3001061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3001061</a>]" pmid="3001061">Tsuji et al. (1986)</a> isolated GBA cDNA clones from a human hepatoma cDNA library. The deduced 516-residue protein has a calculated molecular mass of 57 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3001061" 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="#97" class="mim-tip-reference" title="Sorge, J., Kuhl, W., West, C., Beutler, E. <strong>Complete correction of the enzymatic defect of type I Gaucher disease fibroblasts by retroviral-mediated gene transfer.</strong> Proc. Nat. Acad. Sci. 84: 906-909, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3547401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3547401</a>] [<a href="https://doi.org/10.1073/pnas.84.4.906" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3547401">Sorge et al. (1987)</a> demonstrated that human GBA cDNA contains 2 potential ATG start codons, with the upstream ATG resulting in a protein with a 39-amino acid signal peptide and the downstream ATG resulting in a protein with a 19-amino acid signal peptide. The corresponding signal peptides differed in their hydrophobicity. Either ATG could function to produce active enzyme in cultured fibroblasts. Functional enzyme activity from either translation products was found predominantly in lysosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3547401" 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="#84" class="mim-tip-reference" title="Reiner, O., Wigderson, M., Horowitz, M. <strong>Structural analysis of the human glucocerebrosidase genes.</strong> DNA 7: 107-116, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3359914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3359914</a>] [<a href="https://doi.org/10.1089/dna.1988.7.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3359914">Reiner et al. (1988)</a> isolated 2 different genomic clones encoding human GBA from a fetal liver library. These clones represented 2 glucocerebrosidase genes, which the authors designated 6-1 and 10-2. The second gene is a putative pseudogene (see below). Both genes had identifiable promoter regions, but the promoter of gene 6-1 was much more efficient than that for gene 10-2 in a chloramphenicol acetyltransferase assay. <a href="#84" class="mim-tip-reference" title="Reiner, O., Wigderson, M., Horowitz, M. <strong>Structural analysis of the human glucocerebrosidase genes.</strong> DNA 7: 107-116, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3359914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3359914</a>] [<a href="https://doi.org/10.1089/dna.1988.7.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3359914">Reiner et al. (1988)</a> stated that both genes appear to be mapped at the same locus (<a href="#17" class="mim-tip-reference" title="Choudary, P. V., Tsuji, S., Martin, B. M., Guild, B. C., Mulligan, R. C., Murray, G. J., Barranger, J. A., Ginns, E. I. <strong>The molecular biology of Gaucher disease and the potential for gene therapy.</strong> Cold Spring Harbor Symp. Quant. Biol. 51: 1047-1052, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3472751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3472751</a>] [<a href="https://doi.org/10.1101/sqb.1986.051.01.121" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3472751">Choudary et al., 1986</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3472751+3359914" 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="#49" class="mim-tip-reference" title="Horowitz, M., Wilder, S., Horowitz, Z., Reiner, O., Gelbart, T., Beutler, E. <strong>The human glucocerebrosidase gene and pseudogene: structure and evolution.</strong> Genomics 4: 87-96, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2914709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2914709</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90319-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2914709">Horowitz et al. (1989)</a> identified 2 GBA mRNA species: a major 2.6-kb transcript and a minor 2.2-kb transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2914709" 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="#76" class="mim-tip-reference" title="O'Neill, R. R., Tokoro, T., Kozak, C. A., Brady, R. O. <strong>Comparison of the chromosomal localization of murine and human glucocerebrosidase genes and of the deduced amino acid sequences.</strong> Proc. Nat. Acad. Sci. 86: 5049-5053, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2740343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2740343</a>] [<a href="https://doi.org/10.1073/pnas.86.13.5049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2740343">O'Neill et al. (1989)</a> found that the human and mouse GBA amino acid sequences share 86% identity. All 5 amino acids known to be essential for normal enzymatic activity are conserved between mouse and man. Only 1 ATG translation initiation signal was present in the mouse sequence, whereas 2 have been reported in the human sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2740343" 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>Pseudogene</em></strong></p><p>
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<a href="#49" class="mim-tip-reference" title="Horowitz, M., Wilder, S., Horowitz, Z., Reiner, O., Gelbart, T., Beutler, E. <strong>The human glucocerebrosidase gene and pseudogene: structure and evolution.</strong> Genomics 4: 87-96, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2914709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2914709</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90319-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2914709">Horowitz et al. (1989)</a> sequenced a GBA pseudogene, which is 96% homologous to the functional gene. Compared to the functional gene, the pseudogene has large deletions within several introns, representing Alu sequences flanked by direct repeats, as well as base pair changes scattered throughout the gene. <a href="#83" class="mim-tip-reference" title="Reiner, O., Horowitz, M. <strong>Differential expression of the human glucocerebrosidase-coding gene.</strong> Gene 73: 469-478, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2468581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2468581</a>] [<a href="https://doi.org/10.1016/0378-1119(88)90511-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2468581">Reiner and Horowitz (1988)</a> found that the promoter of the glucocerebrosidase pseudogene has demonstrable activity when attached to a reporter gene. They commented that mutations in the rest of the gene must render the mRNA vulnerable to breakdown or other functional abnormality such that no enzyme is synthesized. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2468581+2914709" 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 studies of RNA from lymphoblasts and fibroblasts from patients with Gaucher disease (see <a href="/entry/230800">230800</a>) and normal subjects, <a href="#96" class="mim-tip-reference" title="Sorge, J., Gross, E., West, C., Beutler, E. <strong>High level transcription of the glucocerebrosidase pseudogene in normal subjects and patients with Gaucher disease.</strong> J. Clin. Invest. 86: 1137-1141, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1698821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1698821</a>] [<a href="https://doi.org/10.1172/JCI114818" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1698821">Sorge et al. (1990)</a> found that the pseudogene was consistently transcribed and that in some cases the level of transcription seemed to be approximately equal to that of the functional gene. The mouse genome did not appear to contain the pseudogene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1698821" 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="#105" class="mim-tip-reference" title="Tayebi, N., Cushner, S., Sidransky, E. <strong>Differentiation of the glucocerebrosidase gene from pseudogene by long-template PCR: implications for Gaucher disease.</strong> Am. J. Hum. Genet. 59: 740-741, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8751878/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8751878</a>]" pmid="8751878">Tayebi et al. (1996)</a> reported a method to distinguish the glucocerebrosidase gene from the pseudogene, which is 2 kb shorter than the expressed gene. The technique involved the use of long-template PCR and PCR primers to simultaneously generate a 5.6-kb fragment from the functional glucocerebrosidase gene and a 3.9-kb fragment from the pseudogene. The PCR products were then individually purified and used in subsequent experiments for mutation detection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8751878" 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="#49" class="mim-tip-reference" title="Horowitz, M., Wilder, S., Horowitz, Z., Reiner, O., Gelbart, T., Beutler, E. <strong>The human glucocerebrosidase gene and pseudogene: structure and evolution.</strong> Genomics 4: 87-96, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2914709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2914709</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90319-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2914709">Horowitz et al. (1989)</a> determined that the GBA gene contains 11 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2914709" 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="#90" class="mim-tip-reference" title="Shafit-Zagardo, B., Devine, E. A., Smith, M., Arredondo-Vega, F., Desnick, R. J. <strong>Assignment of the gene for acid beta-glucosidase to human chromosome 1.</strong> Am. J. Hum. Genet. 33: 564-575, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6455062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6455062</a>]" pmid="6455062">Shafit-Zagardo et al. (1981)</a> assigned the GBA gene to chromosome 1p11-qter. <a href="#22" class="mim-tip-reference" title="Devine, E. A., Smith, M., Arredondo-Vega, F. X., Shafit-Zagardo, B., Desnick, R. J. <strong>Regional assignment of the structural gene for human acid beta-glucosidase to q42-qter on chromosome 1.</strong> Cytogenet. Cell Genet. 33: 340-344, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6816512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6816512</a>] [<a href="https://doi.org/10.1159/000131781" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6816512">Devine et al. (1982)</a> narrowed the assignment to 1q42-qter. By study of hamster-human somatic cell hybrids, <a href="#5" class="mim-tip-reference" title="Barneveld, R. A., Keijzer, W., Tegelaers, F. P. W., Ginns, E. I., Geurts van Kessel, A., Brady, R. O., Barranger, J. A., Tager, J. M., Galjaard, H., Westerveld, A., Reuser, A. J. J. <strong>Assignment of the gene coding for human beta-glucocerebrosidase to the region q21-q31 of chromosome 1 using monoclonal antibodies.</strong> Hum. Genet. 64: 227-231, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6885065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6885065</a>] [<a href="https://doi.org/10.1007/BF00279398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6885065">Barneveld et al. (1983)</a> assigned GBA to 1q21-q31, which was consistent with the studies of <a href="#90" class="mim-tip-reference" title="Shafit-Zagardo, B., Devine, E. A., Smith, M., Arredondo-Vega, F., Desnick, R. J. <strong>Assignment of the gene for acid beta-glucosidase to human chromosome 1.</strong> Am. J. Hum. Genet. 33: 564-575, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6455062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6455062</a>]" pmid="6455062">Shafit-Zagardo et al. (1981)</a> but not with those of <a href="#22" class="mim-tip-reference" title="Devine, E. A., Smith, M., Arredondo-Vega, F. X., Shafit-Zagardo, B., Desnick, R. J. <strong>Regional assignment of the structural gene for human acid beta-glucosidase to q42-qter on chromosome 1.</strong> Cytogenet. Cell Genet. 33: 340-344, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6816512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6816512</a>] [<a href="https://doi.org/10.1159/000131781" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6816512">Devine et al. (1982)</a>. Three studies suggested localization of the GBA gene in distal 1q31 or proximal subband 1q32.1 (<a href="#81" class="mim-tip-reference" title="Philip, N., Mattei, M. G., Baeteman, M. A., Pellissier, M. C., Mattei, J. F. <strong>Precise localization of beta-glucosidase to band q31 of chromosome 1. (Abstract)</strong> Cytogenet. Cell Genet. 40: 723 only, 1985."None>Philip et al., 1985</a>). By somatic cell hybridization and in situ hybridization, <a href="#36" class="mim-tip-reference" title="Ginns, E. I., Choudary, P. V., Tsuji, S., Martin, B., Stubblefield, B., Sawyer, J., Hozier, J., Barranger, J. A. <strong>Gene mapping and leader polypeptide sequence of human glucocerebrosidase: implications for Gaucher disease.</strong> Proc. Nat. Acad. Sci. 82: 7101-7105, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3863141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3863141</a>] [<a href="https://doi.org/10.1073/pnas.82.20.7101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3863141">Ginns et al. (1985)</a> placed GBA at 1q21. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3863141+6816512+6455062+6885065" 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="#19" class="mim-tip-reference" title="Cormand, B., Montfort, M., Chabas, A., Vilageliu, L., Grinberg, D. <strong>Genetic fine localization of the beta-glucocerebrosidase (GBA) and prosaposin (PSAP) genes: implications for Gaucher disease.</strong> Hum. Genet. 100: 75-79, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9225972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9225972</a>] [<a href="https://doi.org/10.1007/s004390050468" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9225972">Cormand et al. (1997)</a> used an intragenic polymorphism of the GBA gene (6144A-G) to localize GBA in relation to markers in the Genethon human linkage map and to a 3.2-cM interval at chromosome 1q21. No recombination was found between 6 markers and the GBA gene. Three of the markers, D1S2777, D1S303, and D1S2140, are present in YAC clone 887h8 which also contains the GBA gene and the PKLR gene (<a href="/entry/609712">609712</a>). <a href="#68" class="mim-tip-reference" title="Mateu, E., Perez-Lezaun, A., Martinez-Arias, R., Andres, A., Valles, M., Bertranpetit, J., Calafell, F. <strong>PKLR-GBA region shows almost complete linkage disequilibrium over 70 kb in a set of worldwide populations.</strong> Hum. Genet. 110: 532-544, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107439</a>] [<a href="https://doi.org/10.1007/s00439-002-0734-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12107439">Mateu et al. (2002)</a> found complete linkage disequilibrium in the PKLR-GBA region over 70 kb in a set of worldwide populations. Variation at PKLR-GBA was also tightly linked to that at the GBA pseudogene. Thus, a 90-kb linkage disequilibrium block was observed, which points to a low recombination rate in this region. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12107439+9225972" 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 linkage studies of interspecific backcrosses of Mus spretus and Mus musculus domesticus, <a href="#89" class="mim-tip-reference" title="Seldin, M. F. <strong>Personal Communication.</strong> Durham, N. C. 3/13/1989."None>Seldin (1989)</a> demonstrated that the Gba gene is located on mouse chromosome 3. <a href="#76" class="mim-tip-reference" title="O'Neill, R. R., Tokoro, T., Kozak, C. A., Brady, R. O. <strong>Comparison of the chromosomal localization of murine and human glucocerebrosidase genes and of the deduced amino acid sequences.</strong> Proc. Nat. Acad. Sci. 86: 5049-5053, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2740343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2740343</a>] [<a href="https://doi.org/10.1073/pnas.86.13.5049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2740343">O'Neill et al. (1989)</a> pointed out that although the NGFB (<a href="/entry/162030">162030</a>) and GBA loci are syntenic in both mouse and the human (they are about 7.6 cM apart on mouse chromosome 3), they represent a conserved segment that spans the centromere in man. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2740343" 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>Pseudogene</em></strong></p><p>
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The GBA pseudogene is located approximately 16 kb downstream from GBA (<a href="#96" class="mim-tip-reference" title="Sorge, J., Gross, E., West, C., Beutler, E. <strong>High level transcription of the glucocerebrosidase pseudogene in normal subjects and patients with Gaucher disease.</strong> J. Clin. Invest. 86: 1137-1141, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1698821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1698821</a>] [<a href="https://doi.org/10.1172/JCI114818" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1698821">Sorge et al., 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1698821" 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="#125" class="mim-tip-reference" title="Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E. <strong>Prediction of severity of Gaucher's disease by identification of mutations at DNA level.</strong> Lancet 334: 349-352, 1989. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569551</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)90536-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2569551">Zimran et al. (1989)</a> identified a new mutation which represented crossing-over between the GBA gene and the pseudogene, resulting in a fusion gene designated 'XOVR.' <a href="#126" class="mim-tip-reference" title="Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E. <strong>A glucocerebrosidase fusion gene in Gaucher disease: implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder.</strong> J. Clin. Invest. 85: 219-222, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2295698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2295698</a>] [<a href="https://doi.org/10.1172/JCI114415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2295698">Zimran et al. (1990)</a> reported that this 'Lepore-like' glucocerebrosidase fusion gene consisted of the 5-prime end of the functional gene and the 3-prime end of the pseudogene. The location of a pseudogene near the functional gene for GBA on chromosome 1q may be the basis of disease-producing changes in the functional gene through gene conversion, similar to what occurs with the CYP21 gene (<a href="/entry/613815">613815</a>) on 6p (<a href="#51" class="mim-tip-reference" title="Horowitz, M. <strong>Personal Communication.</strong> Jerusalem, Israel 6/12/1990."None>Horowitz, 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2295698+2569551" 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="#82" class="mim-tip-reference" title="Reczek, D., Schwake, M., Schroder, J., Hughes, H., Blanz, J., Jin, X., Brondyk, W., Van Patten, S., Edmunds, T., Saftig, P. <strong>LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase.</strong> Cell 131: 770-783, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18022370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18022370</a>] [<a href="https://doi.org/10.1016/j.cell.2007.10.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18022370">Reczek et al. (2007)</a> found that LIMP2 (SCARB2; <a href="/entry/602257">602257</a>) bound beta-GC, but not alpha-galactosidase (GLA; <a href="/entry/300644">300644</a>) or alpha-glucosidase (GAA; <a href="/entry/606800">606800</a>). Beta-GC and LIMP2 interacted in the endoplasmic reticulum, and both proteins traversed the Golgi and endocytic compartments together en route to lysosomes. In vitro, low pH attenuated binding between the 2 proteins, suggesting that acidic lysosomal pH facilitates dissociation of beta-GC from LIMP2. Cross-linking experiments with transfected COS cells suggested that the beta-GC-LIMP2 complex is about 250 kD in size, consistent with a 2:2 beta-GC:LIMP2 stoichiometry. Mutation analysis revealed that a coiled-coil motif within the luminal domain of LIMP2 was required for beta-GC binding. Knockdown of LIMP2 in HeLa cells via small interfering RNA significantly reduced lysosomal beta-GC content and resulted in mistargeting of beta-GC for secretion. Limp2 knockout in mice significantly reduced beta-GC content in liver and kidney, but had no effect on beta-GC mRNA. Limp2 -/- mice, but not wildtype mice, showed elevated serum beta-GC and increased GlcCer content in liver and lung, but not in kidney, spleen, and brain. Limp2 -/- mice did not show a robust Gaucher-like phenotype. <a href="#82" class="mim-tip-reference" title="Reczek, D., Schwake, M., Schroder, J., Hughes, H., Blanz, J., Jin, X., Brondyk, W., Van Patten, S., Edmunds, T., Saftig, P. <strong>LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase.</strong> Cell 131: 770-783, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18022370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18022370</a>] [<a href="https://doi.org/10.1016/j.cell.2007.10.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18022370">Reczek et al. (2007)</a> concluded that LIMP2 functions as a mannose-6-phosphate-independent receptor for lysosomal targeting of beta-GC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18022370" 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>An association between Gaucher disease and Parkinson disease (PD; <a href="/entry/168600">168600</a>; see MOLECULAR GENETICS) has been demonstrated by the concurrence of PD in some Gaucher disease patients and the identification of GBA mutations in some probands with sporadic PD. <a href="#87" class="mim-tip-reference" title="Ron, I., Rapaport, D., Horowitz, M. <strong>Interaction between parkin and mutant glucocerebrosidase variants: a possible link between Parkinson disease and Gaucher disease.</strong> Hum. Molec. Genet. 19: 3771-3781, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20643691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20643691</a>] [<a href="https://doi.org/10.1093/hmg/ddq292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20643691">Ron et al. (2010)</a> showed that mutant GBA variants associated with parkin (PARK2; <a href="/entry/602544">602544</a>), and that wildtype parkin, but not its RING finger mutants, affected the stability of mutant GBA variants. Parkin also promoted the accumulation of mutant GBA in aggresome-like structures and was involved in lys48 (K48)-mediated polyubiquitination of GBA mutants, thus indicating its function as an E3 ligase. The authors suggested that involvement of parkin in the degradation of mutant GBA may explain the concurrence of Gaucher disease and PD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20643691" 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="#56" class="mim-tip-reference" title="Jovic, M., Kean, M. J., Szentpetery, Z., Polevoy, G., Gingras, A.-C., Brill, J. A., Balla, T. <strong>Two phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, beta-glucocerebrosidase.</strong> Molec. Biol. Cell 23: 1533-1545, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22337770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22337770</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22337770[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/10.1091/mbc.E11-06-0553" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22337770">Jovic et al. (2012)</a> found that PI4KII-alpha (PI4K2A; <a href="/entry/609763">609763</a>) and PI4KIII-beta (PI4KB; <a href="/entry/602758">602758</a>), both of which synthesize phosphatidylinositol-4-phosphate (PtdIns4P), had distinct and sequential roles in the lysosomal delivery of beta-GC and LIMP2. Activity of PI4KIII-beta at the Golgi was required to drive exit of LIMP2 from the Golgi, whereas PI4KII-alpha at the trans-Golgi network regulated sorting of LIMP2 toward the late endosome/lysosome compartment. Knockdown or inhibition of PI3KIII-beta led to accumulation of LIMP2 at the Golgi compartment, and knockdown of either LIMP2 or PI4KII-alpha increased beta-GC secretion. Mutations in PI4KII-alpha that disrupted its association with AP3 (see AP3B1, <a href="/entry/603401">603401</a>) disrupted lysosomal LIMP2 targeting. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22337770" 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 combining genetic perturbation of sphingolipid metabolism with quantification of TLR (see <a href="/entry/601194">601194</a>) signaling steps and mass spectrometry-based lipidomics in mouse cells, <a href="#59" class="mim-tip-reference" title="Koberlin, M. S., Snijder, B., Heinz, L. X., Baumann, C. L., Fauster, A., Vladimer, G. I., Gavin, A.-C., Superti-Furga, G. <strong>A conserved circular network of coregulated lipids modulates innate immune responses.</strong> Cell 162: 170-183, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26095250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26095250</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26095250[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2015.05.051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26095250">Koberlin et al. (2015)</a> uncovered a circular network of coregulated sphingolipids and glycerophospholipids. Quantitative lipidomics on fibroblasts from patients with mutations in GBA, GALC (<a href="/entry/606890">606890</a>), ASAH1 (<a href="/entry/613468">613468</a>), or LYST (<a href="/entry/606897">606897</a>) revealed conservation of the circular organization of lipid coregulation across species, cell types, and genetic perturbations. The functional annotation accurately predicted TLR-mediated inflammatory responses, in terms of changes in lipid abundance and lipid species, in patient cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26095250" 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="#77" class="mim-tip-reference" title="Panicker, L. M., Srikanth, M. P., Castro-Gomes, T., Miller, D., Andrews, N. W., Feldman, R. A. <strong>Gaucher disease iPSC-derived osteoblasts have developmental and lysosomal defects that impair bone matrix deposition.</strong> Hum. Molec. Genet. 27: 811-822, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29301038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29301038</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29301038[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddx442" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29301038">Panicker et al. (2018)</a> found that GBA1 deficiency did not appear to interfere with the ability of induced pluripotent stem cells (iPSCs) from Gaucher disease (GD; see <a href="/entry/230800">230800</a>) patients to differentiate efficiently to mesenchymal stem cells (MSCs), but that it did interfere with differentiation from MSCs to osteoblasts and osteoblast bone-forming ability. GD iPSC osteoblasts had defective Wnt/beta-catenin signaling by mutant GBA1, which likely contributed to the defect in GD osteoblast differentiation. GD osteoblast differentiation could be restored by treatment with a potent inhibitor of GSK3-beta (<a href="/entry/605004">605004</a>). Assessment of the integrity of the lysosomal compartment in GD osteoblasts showed that mutant GBA1 had deleterious effects on the osteoblast lysosomal compartment, as Ca(2+)-dependent exocytosis, a lysosomal function critically required for bone matrix deposition, was significantly impaired. Furthermore, the lysosomal compartment in GD iPSC osteoblasts had defects in plasma membrane repair, another lysosome-dependent function important for osteoblast survival. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29301038" 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>The numbering system used for some of the mutations in the MOLECULAR GENETICS and ALLELIC VARIANTS sections in this entry is based on the mature GBA protein and does not include the 39-residue signal peptide.</p><p><strong><em>Gaucher Disease, Types I, II, and III</em></strong></p><p>
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Nearly 200 mutations in the GBA gene have been described in patients with Gaucher disease types I (GD1; <a href="/entry/230800">230800</a>), II (GD2; <a href="/entry/230900">230900</a>), and III (GD3; <a href="/entry/231000">231000</a>) (<a href="#55" class="mim-tip-reference" title="Jmoudiak, M., Futerman, A. H. <strong>Gaucher disease: pathological mechanisms and modern management.</strong> Brit. J. Haemat. 129: 178-188, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15813845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15813845</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.05351.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15813845">Jmoudiak and Futerman, 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15813845" 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="#110" class="mim-tip-reference" title="Tsuji, S., Choudary, P. V., Martin, B. M., Stubblefield, B. K., Mayor, J. A., Barranger, J. A., Ginns, E. I. <strong>A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease.</strong> New Eng. J. Med. 316: 570-575, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2880291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2880291</a>] [<a href="https://doi.org/10.1056/NEJM198703053161002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2880291">Tsuji et al. (1987)</a> identified a mutation in the GBA gene (L444P; <a href="#0001">606463.0001</a>) in patients with Gaucher disease types I, II, and III. Two of the 5 patients with type II and 7 of the 11 with type III were homozygous for this mutation, whereas 4 of 20 patients with type I Gaucher disease had this mutant allele in heterozygous state. The L444P substitution occurs naturally in the GBA pseudogene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2880291" 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="#65" class="mim-tip-reference" title="Latham, T., Grabowski, G. A., Theophilus, B. D. M., Smith, F. I. <strong>Complex alleles of the acid beta-glucosidase gene in Gaucher disease.</strong> Am. J. Hum. Genet. 47: 79-86, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349952</a>]" pmid="2349952">Latham et al. (1990)</a> presented a useful diagram of 9 mutations in the GBA gene identified in patients with Gaucher disease. Four of the mutations (L444P; D409H; <a href="#0006">606463.0006</a>, A456P and V460V; <a href="#0009">606463.0009</a>) were known to be present also in the pseudogene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2349952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Beutler, E. <strong>Gaucher disease as a paradigm of current issues regarding single gene mutations of humans.</strong> Proc. Nat. Acad. Sci. 90: 5384-5390, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8516282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8516282</a>] [<a href="https://doi.org/10.1073/pnas.90.12.5384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8516282">Beutler (1993)</a>, <a href="#71" class="mim-tip-reference" title="Mistry, P. K., Cox, T. M. <strong>The glucocerebrosidase locus in Gaucher's disease: molecular analysis of a lysosomal enzyme.</strong> J. Med. Genet. 30: 889-894, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8301642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8301642</a>] [<a href="https://doi.org/10.1136/jmg.30.11.889" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8301642">Mistry and Cox (1993)</a>, <a href="#50" class="mim-tip-reference" title="Horowitz, M., Zimran, A. <strong>Mutations causing Gaucher disease.</strong> Hum. Mutat. 3: 1-11, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8118460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8118460</a>] [<a href="https://doi.org/10.1002/humu.1380030102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8118460">Horowitz and Zimran (1994)</a>, <a href="#6" class="mim-tip-reference" title="Beutler, E., Demina, A., Gelbart, T. <strong>Glucocerebrosidase mutations in Gaucher disease.</strong> Molec. Med. 1: 82-92, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8790604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8790604</a>]" pmid="8790604">Beutler et al. (1994)</a>, <a href="#12" class="mim-tip-reference" title="Beutler, E., Gelbart, T. <strong>Glucocerebrosidase (Gaucher disease).</strong> Hum. Mutat. 8: 207-213, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8889578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8889578</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)8:3<207::AID-HUMU2>3.0.CO;2-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8889578">Beutler and Gelbart (1996)</a>, and <a href="#100" class="mim-tip-reference" title="Stone, D. L., Tayebi, N., Orvisky, E., Stubblefield, B., Madike, V., Sidransky, E. <strong>Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease.</strong> Hum. Mutat. 15: 181-188, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10649495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10649495</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200002)15:2<181::AID-HUMU7>3.0.CO;2-S" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10649495">Stone et al. (2000)</a> provided updates on mutations in the GBA gene causing Gaucher disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8790604+10649495+8516282+8118460+8889578+8301642" 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 analysis of 60 type I and type III Gaucher patients, <a href="#92" class="mim-tip-reference" title="Sidransky, E., Bottler, A., Stubblefield, B., Ginns, E. I. <strong>DNA mutational analysis of type 1 and type 3 Gaucher patients: how well do mutations predict phenotype?</strong> Hum. Mutat. 3: 25-28, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8118463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8118463</a>] [<a href="https://doi.org/10.1002/humu.1380030105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8118463">Sidransky et al. (1994)</a> found that the 5 most common Gaucher mutations, N370S (<a href="#0003">606463.0003</a>), L444P, R463C (<a href="#0008">606463.0008</a>), 84insG, (<a href="#0014">606463.0014</a>) and IVS2+1G-A (<a href="#0015">606463.0015</a>), were identified in patients with or without neurologic manifestations. The findings indicated that Gaucher patients sharing identical genotypes can exhibit considerable clinical heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8118463" 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="#42" class="mim-tip-reference" title="Grace, M. E., Desnick, R. J., Pastores, G. M. <strong>Identification and expression of acid beta-glucosidase mutations causing severe type 1 and neurologic type 2 Gaucher disease in non-Jewish patients.</strong> J. Clin. Invest. 99: 2530-2537, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9153297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9153297</a>] [<a href="https://doi.org/10.1172/JCI119437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9153297">Grace et al. (1997)</a> identified 6 new pathogenic mutations in the GBA gene in 5 severely affected type I and type II Gaucher disease patients of non-Jewish descent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9153297" 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="#95" class="mim-tip-reference" title="Sidransky, E., Tayebi, N., Stubblefield, B. K., Eliason, W., Klineburgess, A., Pizzolato, G.-P., Cox, J. N., Porta, J., Bottani, A., DeLozier-Blanchet, C. D. <strong>The clinical, molecular, and pathological characterisation of a family with two cases of lethal perinatal type 2 Gaucher disease.</strong> J. Med. Genet. 33: 132-136, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8929950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8929950</a>] [<a href="https://doi.org/10.1136/jmg.33.2.132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8929950">Sidransky et al. (1996)</a> described homozygosity for a triply mutant GBA allele (<a href="#0009">606463.0009</a>) in 2 conceptuses from an Afghan family with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>). The findings were comparable to those in the 'knockout' Gaucher mouse in which absence of enzyme was incompatible with long survival (<a href="#113" class="mim-tip-reference" title="Tybulewicz, V. L. J., Tremblay, M. L., LaMarca, M. E., Willemsen, R., Stubblefield, B. K., Winfield, S., Zablocka, B., Sidransky, E., Martin, B. M., Huang, S. P., Mintzer, K. A., Westphal, H., Mulligan, R. C., Ginns, E. I. <strong>Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene.</strong> Nature 357: 407-410, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1594045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1594045</a>] [<a href="https://doi.org/10.1038/357407a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1594045">Tybulewicz et al., 1992</a>). In an infant with perinatal lethal Gaucher disease, <a href="#104" class="mim-tip-reference" title="Tayebi, N., Cushner, S. R., Kleijer, W., Lau, E. K., Damschroder-Williams, P. J., Stubblefield, B. K., Den Hollander, J., Sidransky, E. <strong>Prenatal lethality of a homozygous null mutation in the human glucocerebrosidase gene.</strong> Am. J. Med. Genet. 73: 41-47, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9375921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9375921</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971128)73:1<41::aid-ajmg9>3.0.co;2-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9375921">Tayebi et al. (1997)</a> identified homozygosity for a null mutation in the GBA gene (<a href="#0034">606463.0034</a>). This case confirmed the essential role of GBA in human development. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8929950+1594045+9375921" 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="#35" class="mim-tip-reference" title="Germain, D. P., Puech, J.-P., Caillaud, C., Kahn, A., Poenaru, L. <strong>Exhaustive screening of the acid beta-glucosidase gene, by fluorescence-assisted mismatch analysis using universal primers: mutation profile and genotype/phenotype correlations in Gaucher disease.</strong> Am. J. Hum. Genet. 63: 415-427, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9683600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9683600</a>] [<a href="https://doi.org/10.1086/301969" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9683600">Germain et al. (1998)</a> described an exhaustive screening strategy, involving fluorescence-assisted mismatch analysis using universal primers, and succeeded in identifying both Gaucher disease mutant alleles in all 25 patients studied. A total of 18 different mutations and a new Gaucher disease haplotype were detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9683600" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with perinatal lethal Gaucher disease, <a href="#41" class="mim-tip-reference" title="Grace, M. E., Ashton-Prolla, P., Pastores, G. M., Soni, A., Desnick, R. J. <strong>Non-pseudogene-derived complex acid beta-glucosidase mutations causing mild type 1 and severe type 2 Gaucher disease.</strong> J. Clin. Invest. 103: 817-823, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10079102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10079102</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10079102[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI5168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10079102">Grace et al. (1999)</a> identified 2 pathogenic alleles in the GBA gene. <a href="#99" class="mim-tip-reference" title="Stone, D. L., Carey, W. F., Christodoulou, J., Sillence, D., Nelson, P., Callahan, M., Tayebi, N., Sidransky, E. <strong>Type 2 Gaucher disease: the collodion baby phenotype revisited.</strong> Arch. Dis. Child. Fetal Neonatal Ed. 82: F163-F166, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10685993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10685993</a>] [<a href="https://doi.org/10.1136/fn.82.2.f163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10685993">Stone et al. (2000)</a> reported 6 children who presented at birth with collodion-type skin changes and hepatosplenomegaly and were found to be beta-glucocerebrosidase-deficient. All died shortly after birth or in the first year of life from respiratory insufficiency or progressive neurologic disease. Three of the cases were homozygous for GBA mutations (see <a href="#0009">606463.0009</a> and <a href="#0042">606463.0042</a>) and the others were compound heterozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10079102+10685993" 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="#80" class="mim-tip-reference" title="Park, J. K., Tayebi, N., Stubblefield, B. K., LaMarca, M. E., MacKenzie, J. J., Stone, D. L., Sidransky, E. <strong>The E326K mutation and Gaucher disease: mutation or polymorphism?</strong> Clin. Genet. 61: 32-34, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11903352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11903352</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.610106.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11903352">Park et al. (2002)</a> noted that an E326K substitution had been identified in patients with all 3 types of Gaucher disease, but in each instance it was found on the same allele with another GBA mutation (see, e.g., <a href="#0011">606463.0011</a>). The authors identified the E326K allele in 1.3% of patients with Gaucher disease and in 0.9% of controls, indicating that it is a polymorphism. <a href="#73" class="mim-tip-reference" title="Montfort, M., Chabas, A., Vilageliu, L., Grinberg, D. <strong>Functional analysis of 13 GBA mutant alleles identified in Gaucher disease patients: pathogenic changes and 'modifier' polymorphisms.</strong> Hum. Mutat. 23: 567-575, 2004. Note: Erratum: Hum. Mutat. 26: 276 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146461</a>] [<a href="https://doi.org/10.1002/humu.20043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146461">Montfort et al. (2004)</a> performed functional analyses of 13 GBA mutant alleles identified in Gaucher disease patients. The mutations were expressed in Sf9 cells using a baculovirus expression system. The authors obtained results suggesting that the E326K mutation should be considered a 'modifier variant' rather than a neutral polymorphism, as previously suggested (<a href="#41" class="mim-tip-reference" title="Grace, M. E., Ashton-Prolla, P., Pastores, G. M., Soni, A., Desnick, R. J. <strong>Non-pseudogene-derived complex acid beta-glucosidase mutations causing mild type 1 and severe type 2 Gaucher disease.</strong> J. Clin. Invest. 103: 817-823, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10079102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10079102</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10079102[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI5168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10079102">Grace et al., 1999</a>; <a href="#80" class="mim-tip-reference" title="Park, J. K., Tayebi, N., Stubblefield, B. K., LaMarca, M. E., MacKenzie, J. J., Stone, D. L., Sidransky, E. <strong>The E326K mutation and Gaucher disease: mutation or polymorphism?</strong> Clin. Genet. 61: 32-34, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11903352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11903352</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.610106.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11903352">Park et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11903352+10079102+15146461" 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="#106" class="mim-tip-reference" title="Tayebi, N., Stubblefield, B. K., Park, J. K., Orvisky, E., Walker, J. M., LaMarca, M. E., Sidransky, E. <strong>Reciprocal and nonreciprocal recombination at the glucocerebrosidase gene region: implications for complexity in Gaucher disease.</strong> Am. J. Hum. Genet. 72: 519-534, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12587096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12587096</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12587096[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/10.1086/367850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12587096">Tayebi et al. (2003)</a> studied DNA samples from 240 patients with Gaucher disease, using several complementary approaches to identify and characterize recombinant alleles. Among 480 alleles studied, 59 recombinant alleles were identified, including 34 gene conversions, 18 fusions, and 7 downstream duplications. At least 1 recombinant allele was present in 22% of the patients. In patients with Gaucher disease types I, II, and III, the authors found recombinant alleles with the following frequencies among alleles: 26 of 310, 18 of 74, and 15 of 96, respectively. Several patients carried 2 recombinations or mutations on the same allele. Generally, alleles resulting from nonreciprocal recombination (gene conversion) could be distinguished from those arising by reciprocal recombination (crossover and exchange), and the length of the converted sequence was determined. Homozygosity for a recombinant allele was associated with early lethality. Ten different sites of crossover and a shared pentamer motif sequence (CACCA) that could be a hotspot for recombination were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12587096" 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="#26" class="mim-tip-reference" title="Emre, S., Gurakan, F., Yuce, A., Rolf, A., Scott, R., Ozen, H. <strong>Molecular analysis of Turkish Gaucher disease patients: identification of novel mutations in glucocerebrosidase (GBA) gene.</strong> Europ. J. Med. Genet. 51: 315-321, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18586596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18586596</a>] [<a href="https://doi.org/10.1016/j.ejmg.2008.02.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18586596">Emre et al. (2008)</a> analyzed the GBA gene in 57 unrelated Turkish patients with Gaucher disease and identified 103 mutant alleles (90.3%) carrying 11 different mutations, 3 of which were novel. The most frequent mutations included L444P (42%), N370S (30%), D409H (4.3%), and R463C (3.5%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18586596" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Late-Onset Parkinson Disease and Lewy Body Dementia</em></strong></p><p>
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<a href="#38" class="mim-tip-reference" title="Goker-Alpan, O., Schiffmann, R., LaMarca, M. E., Nussbaum, R. L., McInerney-Leo, A., Sidransky, E. <strong>Parkinsonism among Gaucher disease carriers.</strong> J. Med. Genet. 41: 937-940, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15591280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15591280</a>] [<a href="https://doi.org/10.1136/jmg.2004.024455" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15591280">Goker-Alpan et al. (2004)</a> reported 10 unrelated families with Gaucher disease in which obligate or confirmed carriers of GBA mutations developed Parkinson disease (see PD, <a href="/entry/168600">168600</a>). In the family of a proband with Gaucher disease type III, the proband's father, paternal grandfather, and paternal great-aunt developed parkinsonism, and all were found to carry the mutant GBA allele that was found in the proband; 2 asymptomatic family members did not have the allele. Nine of 40 additional families with Gaucher disease had similar findings, but there was no correlation with specific GBA mutations. Most of the patients with parkinsonism developed neurocognitive changes. <a href="#38" class="mim-tip-reference" title="Goker-Alpan, O., Schiffmann, R., LaMarca, M. E., Nussbaum, R. L., McInerney-Leo, A., Sidransky, E. <strong>Parkinsonism among Gaucher disease carriers.</strong> J. Med. Genet. 41: 937-940, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15591280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15591280</a>] [<a href="https://doi.org/10.1136/jmg.2004.024455" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15591280">Goker-Alpan et al. (2004)</a> suggested that heterozygosity for mutations in the GBA gene may be a risk factor for the development of parkinsonism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15591280" 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="Aharon-Peretz, J., Rosenbaum, H., Gershoni-Baruch, R. <strong>Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.</strong> New Eng. J. Med. 351: 1972-1977, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15525722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15525722</a>] [<a href="https://doi.org/10.1056/NEJMoa033277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15525722">Aharon-Peretz et al. (2004)</a> reported an association between Parkinson disease and mutations in the GBA gene in Ashkenazi Jews by screening for 6 GBA mutations most common among this population. One or 2 mutant GBA alleles were identified in 31 (31.3%) of 99 Ashkenazi patients with idiopathic PD: 28 were heterozygous and 3 were homozygous for one of these mutations. Among 74 Ashkenazi patients with Alzheimer disease (AD; <a href="/entry/104300">104300</a>), 3 (4.1%) were carriers of Gaucher disease and among 1,543 controls, 95 (6.2%) were carriers of Gaucher disease. Patients with PD had significantly greater odds of being carriers of Gaucher disease than did patients with Alzheimer disease (OR = 10.8) or controls (OR = 7.0). Among PD patients, those who were carriers of Gaucher disease were younger than those who were not carriers (mean age at onset, 60.0 years vs 64.2 years, respectively). <a href="#3" class="mim-tip-reference" title="Aharon-Peretz, J., Rosenbaum, H., Gershoni-Baruch, R. <strong>Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.</strong> New Eng. J. Med. 351: 1972-1977, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15525722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15525722</a>] [<a href="https://doi.org/10.1056/NEJMoa033277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15525722">Aharon-Peretz et al. (2004)</a> suggested that some GBA mutations are susceptibility factors for Parkinson disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15525722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Aharon-Peretz, J., Badarny, S., Rosenbaum, H., Gershoni-Baruch, R. <strong>Mutations in the glucocerebrosidase gene and Parkinson disease: phenotype-genotype correlation.</strong> Neurology 65: 1460-1461, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16148263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16148263</a>] [<a href="https://doi.org/10.1212/01.wnl.0000176987.47875.28" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16148263">Aharon-Peretz et al. (2005)</a> observed no difference in overall clinical manifestations and age at disease onset between 40 Ashkenazi Jewish PD patients who carried GBA mutations and 108 Ashkenazi Jewish PD patients without GBA mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16148263" 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="#109" class="mim-tip-reference" title="Toft, M., Pielsticker, L., Ross, O. A., Aasley, J. O., Farrer, M. J. <strong>Glucocerebrosidase gene mutations and Parkinson disease in the Norwegian population.</strong> Neurology 66: 415-417, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16476943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16476943</a>] [<a href="https://doi.org/10.1212/01.wnl.0000196492.80676.7c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16476943">Toft et al. (2006)</a> did not find an association between PD and 2 common GBA mutations, L444P and N370S, among 311 Norwegian patients with Parkinson disease. Mutant GBA alleles were identified in 7 (2.3%) patients and 8 (1.7%) controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16476943" 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="#37" class="mim-tip-reference" title="Goker-Alpan, O., Giasson, B. I., Eblan, M. J., Nguyen, J., Hurtig, H. I., Lee, V. M.-Y., Trojanowski, J. Q., Sidransky, E. <strong>Glucocerebrosidase mutations are an important risk factor for Lewy body disorders.</strong> Neurology 67: 908-910, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16790605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16790605</a>] [<a href="https://doi.org/10.1212/01.wnl.0000230215.41296.18" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16790605">Goker-Alpan et al. (2006)</a> identified heterozygous mutations in the GBA gene in 8 (23%) of 35 patients with dementia with Lewy bodies (DLB; <a href="/entry/127750">127750</a>). Four of these individuals carried the N370S mutation. One of 28 patients with Parkinson disease also carried a heterozygous N370S mutation. The authors postulated that a mutant GBA enzyme may take on a different and unexpected role that may contribute to the development of synucleinopathies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16790605" 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="#103" class="mim-tip-reference" title="Tan, E.-K., Tong, J., Fook-Chong, S., Yih, Y., Wong, M.-C., Pavanni, R., Zhao, Y. <strong>Glucocerebrosidase mutations and risk of Parkinson disease in Chinese patients.</strong> Arch. Neurol. 64: 1056-1058, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17620502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17620502</a>] [<a href="https://doi.org/10.1001/archneur.64.7.1056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17620502">Tan et al. (2007)</a> identified a heterozygous L444P mutation in 8 (2.4%) of 331 Chinese patients with typical Parkinson disease and none of 347 controls. The age at onset was lower and the percentage of women higher in patients with the L444P mutation compared to those without the mutation. <a href="#103" class="mim-tip-reference" title="Tan, E.-K., Tong, J., Fook-Chong, S., Yih, Y., Wong, M.-C., Pavanni, R., Zhao, Y. <strong>Glucocerebrosidase mutations and risk of Parkinson disease in Chinese patients.</strong> Arch. Neurol. 64: 1056-1058, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17620502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17620502</a>] [<a href="https://doi.org/10.1001/archneur.64.7.1056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17620502">Tan et al. (2007)</a> noted that the findings were significant because Gaucher disease is extremely rare among the Chinese. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17620502" 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="#34" class="mim-tip-reference" title="Gan-Or, Z., Giladi, N., Rozovski, U., Shifrin, C., Rosner, S., Gurevich, T., Bar-Shira, A., Orr-Urtreger, A. <strong>Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset.</strong> Neurology 70: 2277-2283, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18434642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18434642</a>] [<a href="https://doi.org/10.1212/01.wnl.0000304039.11891.29" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18434642">Gan-Or et al. (2008)</a> found that 75 (17.9%) of 420 Ashkenazi Jewish patients with PD carried a GBA mutation, compared to 4.2% of elderly and 6.35% of young controls. The proportion of severe GBA mutation carriers among patients was 29% compared to 7% among young controls. Severe and mild GBA mutations increased the risk of developing PD by 13.6- and 2.2-fold, and were associated with decreased age at PD onset. <a href="#34" class="mim-tip-reference" title="Gan-Or, Z., Giladi, N., Rozovski, U., Shifrin, C., Rosner, S., Gurevich, T., Bar-Shira, A., Orr-Urtreger, A. <strong>Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset.</strong> Neurology 70: 2277-2283, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18434642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18434642</a>] [<a href="https://doi.org/10.1212/01.wnl.0000304039.11891.29" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18434642">Gan-Or et al. (2008)</a> concluded that genetic variance in the GBA gene is a risk factor for PD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18434642" 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="#45" class="mim-tip-reference" title="Gutti, U., Fung, H.-C., Hruska, K. S., LaMarca, M. E., Chen, C.-M., Wu, Y.-R., Sidransky, E. <strong>The need for appropriate genotyping strategies for glucocerebrosidase mutations in cohorts with Parkinson disease. (Letter)</strong> Arch. Neurol. 65: 850-851, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18541817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18541817</a>] [<a href="https://doi.org/10.1001/archneur.65.6.850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18541817">Gutti et al. (2008)</a> identified the L444P mutation in 4 (2.2%) of 184 Taiwanese patients with PD. Six other GBA variants were identified in 1 patient each, yielding a total of 7 different mutations in 10 patients (5.4%). <a href="#45" class="mim-tip-reference" title="Gutti, U., Fung, H.-C., Hruska, K. S., LaMarca, M. E., Chen, C.-M., Wu, Y.-R., Sidransky, E. <strong>The need for appropriate genotyping strategies for glucocerebrosidase mutations in cohorts with Parkinson disease. (Letter)</strong> Arch. Neurol. 65: 850-851, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18541817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18541817</a>] [<a href="https://doi.org/10.1001/archneur.65.6.850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18541817">Gutti et al. (2008)</a> suggested that sequencing the entire GBA gene would reveal additional variant that may contribute to PD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18541817" 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="#67" class="mim-tip-reference" title="Mata, I. F., Samii, A., Schneer, S. H., Roberts, J. W., Griffith, A., Leis, B. C., Schellenberg, G. D., Sidransky, E., Bird, T. D., Leverenz, J. B., Tsuang, D., Zabetian, C. P. <strong>Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.</strong> Arch. Neurol. 65: 379-382, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18332251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18332251</a>] [<a href="https://doi.org/10.1001/archneurol.2007.68" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18332251">Mata et al. (2008)</a> identified heterozygosity for either the L444P or N370S mutation in 21 (2.9%) of 721 PD patients, 2 (3.5%) of 57 DLB patients, and 2 (0.4%) of 554 control individuals, all of European origin. <a href="#67" class="mim-tip-reference" title="Mata, I. F., Samii, A., Schneer, S. H., Roberts, J. W., Griffith, A., Leis, B. C., Schellenberg, G. D., Sidransky, E., Bird, T. D., Leverenz, J. B., Tsuang, D., Zabetian, C. P. <strong>Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.</strong> Arch. Neurol. 65: 379-382, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18332251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18332251</a>] [<a href="https://doi.org/10.1001/archneurol.2007.68" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18332251">Mata et al. (2008)</a> estimated that the population-attributable risk for GBA mutations in Lewy body disorders was only about 3% in patients of European ancestry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18332251" 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="#75" class="mim-tip-reference" title="Nichols, W. C., Pankratz, N., Marek, D. K., Pauciulo, M. W., Elsaesser, V. E., Halter, C. A., Rudolph, A., Wojcieszek, J., Pfeiffer, R. F., Foroud, T. <strong>Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset.</strong> Neurology 72: 310-316, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18987351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18987351</a>] [<a href="https://doi.org/10.1212/01.wnl.0000327823.81237.d1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18987351">Nichols et al. (2009)</a> identified 9 different mutations in the GBA gene, including 5 previously reported variants, in 161 (12.2%) of 1,325 patients with Parkinson disease from 99 (17.5%) of 566 PD families, respectively. Statistical analysis indicated that presence of 1 of the 5 previously reported GBA mutation was associated with increased risk of PD as well as earlier age at disease onset compared to controls without a GBA mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18987351" 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 16-center worldwide study comprising 5,691 PD patients (including 780 Ashkenazi Jewish patients) and 4,898 controls (387 Ashkenazis), <a href="#93" class="mim-tip-reference" title="Sidransky, E., Nalls, M. A., Aasly, J. O., Aharon-Peretz, J., Annesi, G., Barbosa, E. R., Bar-Shira, A., Berg, D., Bras, J., Brice, A., Chen, C.-M., Clark, L. N., and 50 others. <strong>Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.</strong> New Eng. J. Med. 361: 1651-1661, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19846850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19846850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19846850[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/10.1056/NEJMoa0901281" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19846850">Sidransky et al. (2009)</a> demonstrated a strong association between GBA mutations and Parkinson disease. Direct sequencing for only the L444P or N370S mutations identified either mutation in 15% of Ashkenazi patients and 3% of Ashkenazi controls. Among non-Ashkenazi individuals, either mutation was found in 3% of patients and less than 1% of controls. However, full gene sequencing identified GBA mutations in 7% of non-Ashkenazi patients. The odds ratio for any GBA mutation in patients compared to controls was 5.43 across all centers. Compared to PD patients without GBA mutations, patients with GBA mutations presented earlier with the disease, were more likely to have affected relatives, and were more more likely to have atypical manifestations, including cognitive defects. <a href="#93" class="mim-tip-reference" title="Sidransky, E., Nalls, M. A., Aasly, J. O., Aharon-Peretz, J., Annesi, G., Barbosa, E. R., Bar-Shira, A., Berg, D., Bras, J., Brice, A., Chen, C.-M., Clark, L. N., and 50 others. <strong>Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.</strong> New Eng. J. Med. 361: 1651-1661, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19846850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19846850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19846850[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/10.1056/NEJMoa0901281" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19846850">Sidransky et al. (2009)</a> concluded that while GBA mutations are not likely a mendelian cause of PD, they do represent a susceptibility factor for development of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19846850" 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="#74" class="mim-tip-reference" title="Neumann, J., Bras, J., Deas, E., O'Sullivan, S. S., Parkkinen, L., Lachmann, R. H., Li, A., Holton, J., Guerreiro, R., Paudel, R., Segarane, B., Singleton, A., Lees, A., Hardy, J., Houlden, H., Revesz, T., Wood, N. W. <strong>Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.</strong> Brain 132: 1783-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286695</a>] [<a href="https://doi.org/10.1093/brain/awp044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19286695">Neumann et al. (2009)</a> identified 14 different heterozygous mutations in the GBA gene in 33 (4.18%) of 790 British patients with Parkinson disease and in 3 (1.17%) of 257 controls. Three novel mutations (see, e.g., D443N; <a href="#0048">606463.0048</a>) were identified, and the most common mutations were L444P (in 11 patients), N370S (in 8 patients), and R463C (in 3 patients). Four (12%) patients had a family history of the disorder, whereas 29 (88%) had sporadic disease. The mean age at onset was 52.7 years, and 12 (39%) patients had onset before age 50. Fifteen (48.39%) of the patients with GBA mutations developed cognitive decline, including visual hallucinations. The male-to-female ratio of GBA carriers within the PD group was 5:2, which was significantly higher than that of the whole study group. Most patients responded initially to L-DOPA treatment. Neuropathologic examination of 17 GBA mutation carriers showed typical PD changes, with widespread and abundant alpha-synuclein pathology, and most also had neocortical Lewy body pathology. The prevalence of GBA mutations in British patients with sporadic PD was 3.7%, indicating that mutations in the GBA gene may be the most common risk factor for development of PD in this population. In an accompanying letter, <a href="#33" class="mim-tip-reference" title="Gan-Or, Z., Giladi, N., Orr-Urteger, A. <strong>Differential phenotype in Parkinson's disease patients with severe versus mild GBA mutations. (Letter)</strong> Brain 132: e125, 2009. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19502295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19502295</a>] [<a href="https://doi.org/10.1093/brain/awp161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19502295">Gan-Or et al. (2009)</a> found that the data presented by <a href="#74" class="mim-tip-reference" title="Neumann, J., Bras, J., Deas, E., O'Sullivan, S. S., Parkkinen, L., Lachmann, R. H., Li, A., Holton, J., Guerreiro, R., Paudel, R., Segarane, B., Singleton, A., Lees, A., Hardy, J., Houlden, H., Revesz, T., Wood, N. W. <strong>Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.</strong> Brain 132: 1783-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286695</a>] [<a href="https://doi.org/10.1093/brain/awp044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19286695">Neumann et al. (2009)</a> indicated that patients with mild GBA mutations had later age at onset (62.9 years vs 49.8 years) and lower frequency of cognitive symptoms (25% vs 55.6%) compared to patients with severe GBA mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19502295+19286695" 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>PD brains are characterized by accumulation of aggregated alpha-synuclein (SNCA; <a href="/entry/163890">163890</a>), in addition to neurodegeneration. <a href="#69" class="mim-tip-reference" title="Mazzulli, J. R., Xu, Y.-H., Sun, Y., Knight, A. L., McLean, P. J., Caldwell, G. A., Sidransky, E., Grabowski, G. A., Krainc, D. <strong>Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies.</strong> Cell 146: 37-52, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21700325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21700325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21700325[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2011.06.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21700325">Mazzulli et al. (2011)</a> found that postmortem brains of patients with GD and features of PD, as well as mouse models of GD, showed neuronal accumulation of SNCA. Functional loss of GCase and resultant GlcCer accumulation in cultured mouse cortical neurons and human neurons reprogrammed from induced pluripotent stem cells resulted in compromised lysosomal degradation of long-lived proteins, including SNCA. Elevated cellular GlcCer also promoted SNCA aggregation. SNCA accumulation in turn inhibited normal lysosomal GCase activity in neurons and PD brain. In apparently normal human cortical samples, SNCA protein content, particularly high molecular mass species, correlated inversely with GCase activity. <a href="#69" class="mim-tip-reference" title="Mazzulli, J. R., Xu, Y.-H., Sun, Y., Knight, A. L., McLean, P. J., Caldwell, G. A., Sidransky, E., Grabowski, G. A., Krainc, D. <strong>Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies.</strong> Cell 146: 37-52, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21700325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21700325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21700325[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2011.06.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21700325">Mazzulli et al. (2011)</a> hypothesized that a positive-feedback loop between defective SNCA and/or GCase could lead to self-propagating neurodegeneration over time. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21700325" 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="#39" class="mim-tip-reference" title="Gonzalez-del Rincon, M. de L., Monroy Jaramillo, N., Suarez Martinez, A. I., Yescas Gomez, P., Boll Woehrlen, M. C., Lopez Lopez, M., Alonso Vilatela, M. E. <strong>The L444P GBA mutation is associated with early-onset Parkinson's disease in Mexican Mestizos. (Letter)</strong> Clin. Genet. 84: 386-387, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23448517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23448517</a>] [<a href="https://doi.org/10.1111/cge.12084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23448517">Gonzalez-del Rincon et al. (2013)</a> identified a heterozygous L444P mutation in 7 (5.5%) of 128 Mexican Mestizo patients with early-onset PD (before 45 years of age) and in none (0%) of 252 ethnically matched controls. Six (85.7%) of the 7 patients had psychiatric symptoms, including major depressive disorder, generalized anxiety disorder, and obsessive compulsive disorder, which was significantly higher than the prevalence of these disorders in controls (24.7%). In addition, 57% of mutation carriers presented with cognitive decline compared to 5.7% of controls. The N370S mutation was not found in any of the Mexican individuals, suggesting a similarity to Asian populations in which the N370S mutation is almost nonexistent. <a href="#39" class="mim-tip-reference" title="Gonzalez-del Rincon, M. de L., Monroy Jaramillo, N., Suarez Martinez, A. I., Yescas Gomez, P., Boll Woehrlen, M. C., Lopez Lopez, M., Alonso Vilatela, M. E. <strong>The L444P GBA mutation is associated with early-onset Parkinson's disease in Mexican Mestizos. (Letter)</strong> Clin. Genet. 84: 386-387, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23448517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23448517</a>] [<a href="https://doi.org/10.1111/cge.12084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23448517">Gonzalez-del Rincon et al. (2013)</a> concluded that the risk for PD conferred by GBA mutations may be higher than previously thought, and that GBA-associated PD may predispose to psychiatric symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23448517" 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="#108" class="mim-tip-reference" title="Theophilus, B., Latham, T., Grabowski, G. A., Smith, F. I. <strong>Gaucher disease: molecular heterogeneity and phenotype-genotype correlations.</strong> Am. J. Hum. Genet. 45: 212-225, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2502917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2502917</a>]" pmid="2502917">Theophilus et al. (1989)</a> confirmed the high frequency of the N370S mutation in Ashkenazi Jewish patients with type I Gaucher disease. Homozygotes were mildly affected older persons, and the mutant allele was not found in any patient with neuronopathic disease. Furthermore, they confirmed that the L444P mutation was the predominant allele in Gaucher disease type II and type III. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2502917" 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="#62" class="mim-tip-reference" title="Koprivica, V., Stone, D. L., Park, J. K., Callahan, M., Frisch, A., Cohen, I. J., Tayebi, N., Sidransky, E. <strong>Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease.</strong> Am. J. Hum. Genet. 66: 1777-1786, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10796875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10796875</a>] [<a href="https://doi.org/10.1086/302925" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10796875">Koprivica et al. (2000)</a> used several approaches, including direct sequencing, Southern blotting, long-template PCR, restriction digestions, and the amplification refraction mutation system, to genotype 128 patients with type I Gaucher disease (64 of Ashkenazi Jewish ancestry and 64 of non-Jewish extraction) and 24 patients with type III Gaucher disease. More than 97% of the mutant alleles were identified. Fourteen novel mutations and many rare mutations were detected. Recombinant alleles were found in 19% of the patients. Four mutations (N370S, 84insG, IVS2+1G-A, and L444P) accounted for 93% of the mutant alleles in the Ashkenazi Jewish type I patients, but for only 49% of mutant alleles in the non-Jewish type I patients. Heterozygosity for N370S resulted in type I Gaucher disease, whereas homozygosity for L444P was associated with type III. Genotype L444P/recombinant allele resulted in type II Gaucher disease, and homozygosity for a recombinant allele was associated with perinatal lethal disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10796875" 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>Homozygosity for the D409H mutation (<a href="/entry/606464#0006">606464.0006</a>) has been reported in Arab (<a href="#1" class="mim-tip-reference" title="Abrahamov, A., Elstein, D., Gross-Tsur, V., Farber, B., Glaser, Y., Hadas-Halpern, I., Ronen, S., Tafakjdi, M., Horowitz, M., Zimram, A. <strong>Gaucher's disease variant characterized by progressive calcification of heart valves and unique genotype.</strong> Lancet 346: 1000-1003, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7475546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7475546</a>] [<a href="https://doi.org/10.1016/s0140-6736(95)91688-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7475546">Abrahamov et al., 1995</a>) and British/German (<a href="#7" class="mim-tip-reference" title="Beutler, E., Gelbart, T., Demina, A., Zimran, A., LeCoutre, P. <strong>Five new Gaucher disease mutations.</strong> Blood Cells Molec. Dis. 21: 20-24, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7655857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7655857</a>] [<a href="https://doi.org/10.1006/bcmd.1995.0004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7655857">Beutler et al., 1995</a>) patients with neuronopathic Gaucher disease and cardiovascular calcifications, a specific subtype known as 'Gaucher disease type IIIC' (<a href="/entry/231005">231005</a>) (<a href="#15" class="mim-tip-reference" title="Bohlega, S., Kambouris, M., Shahid, M., Al Homsi, M., Al Sous, W. <strong>Gaucher disease with oculomotor apraxia and cardiovascular calcification (Gaucher type IIIC).</strong> Neurology 54: 261-263, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10636167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10636167</a>] [<a href="https://doi.org/10.1212/wnl.54.1.261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10636167">Bohlega et al., 2000</a>). These reports demonstrate a particularly tight pan-ethnic association between phenotype and genotype in this variant form of Gaucher disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7655857+7475546+10636167" 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="#86" class="mim-tip-reference" title="Ron, I., Horowitz, M. <strong>ER retention and degradation as the molecular basis underlying Gaucher disease heterogeneity.</strong> Hum. Molec. Genet. 14: 2387-2398, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16000318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16000318</a>] [<a href="https://doi.org/10.1093/hmg/ddi240" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16000318">Ron and Horowitz (2005)</a> tested glucocerebrosidase protein levels, N-glycans processing, and intracellular localization in skin fibroblasts derived from patients with Gaucher disease. Their results strongly suggested that mutant glucocerebrosidase variants presented variable levels of ER retention and underwent ER-associated degradation in the proteasomes. The degree of ER retention and proteasomal degradation was 1 of the factors that determined Gaucher disease severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16000318" 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 review of the molecular genetics of Gaucher disease, <a href="#52" class="mim-tip-reference" title="Hruska, K. S., LaMarca, M. E., Scott, C. R., Sidransky, E. <strong>Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA).</strong> Hum. Mutat. 29: 567-583, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18338393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18338393</a>] [<a href="https://doi.org/10.1002/humu.20676" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18338393">Hruska et al. (2008)</a> noted that most GBA mutations can be found in patients with various forms of the disorder. The phenotype is mainly determined by the combination of mutations on both alleles; thus the prediction of phenotype from genotypic data has limited utility. In addition, it has become increasingly difficult to categorize patients into 1 of the 3 classic types of Gaucher disease, indicating that the phenotypes fall into a continuum, with the major distinction being the presence and degree of neurologic function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18338393" 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="#14" class="mim-tip-reference" title="Beutler, E. <strong>Gaucher disease as a paradigm of current issues regarding single gene mutations of humans.</strong> Proc. Nat. Acad. Sci. 90: 5384-5390, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8516282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8516282</a>] [<a href="https://doi.org/10.1073/pnas.90.12.5384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8516282">Beutler (1993)</a> stated that the 2 most common mutations in the Ashkenazi Jewish population were N370S and 84insG, representing approximately 77% and 13% of mutant alleles, respectively. These 2 mutations, together with L444P, IVS2+1G-A, and V394L (<a href="#0005">606463.0005</a>), account for 98% of the disease-causing alleles in this population. Each of these mutations was found in the context of a single haplotype, consistent with a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8516282" 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="#23" class="mim-tip-reference" title="Diaz, G. A., Gelb, B. D., Risch, N., Nygaard, T. G., Frisch, A., Cohen, I. J., Sa Miranda, C., Amaral, O., Maire, I., Poenaru, L., Caillaud, C., Weizberg, M., Mistry, P., Desnick, R. J. <strong>Gaucher disease: the origins of the Ashkenazi Jewish N370S and 84GG acid beta-glucosidase mutations.</strong> Am. J. Hum. Genet. 66: 1821-1832, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10777718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10777718</a>] [<a href="https://doi.org/10.1086/302946" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10777718">Diaz et al. (2000)</a> used short tandem repeat (STR) markers to map a 9.3-cM region containing the GBA locus and to genotype 261 Ashkenazi Jewish N370S chromosomes, 60 European non-Jewish N370S chromosomes, and 62 Ashkenazi Jewish 84insG chromosomes. A highly conserved haplotype at 4 markers flanking GBA was observed on both the Ashkenazi chromosomes and the non-Jewish N370S chromosomes, suggesting the occurrence of a founder common to the 2 populations. The presence of different divergent haplotypes suggested the occurrence of de novo, recurrent N370S mutations. In contrast, a different conserved haplotype at these markers was identified on the 84insG chromosomes, which was unique to the Ashkenazi population. On the basis of linkage disequilibrium values, the non-Jewish European N370S chromosomes had greater haplotype diversity and less linkage disequilibrium at the markers flanking the conserved haplotype than did the Ashkenazi N370S chromosomes. This finding was considered consistent with the presence of the N370S mutation in the non-Jewish European population before the founding of the Ashkenazi population. Coalescence analyses for the N370S and 84GG mutations estimated similar coalescence times, of 48 and 55.5 generations ago, respectively. (Coalescence time refers to the number of generations to the most recent common ancestor, MRCA.) The results of these studies were consistent with a significant bottleneck occurring in the Ashkenazi population during the first millennium, when the population became established. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10777718" 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 naturally occurring canine model of Gaucher disease was reported by <a href="#116" class="mim-tip-reference" title="van de Water, N. S., Jolly, R. D., Farrow, B. R. H. <strong>Canine Gaucher disease--the enzyme defect.</strong> Aust. J. Exp. Biol. Med. Sci. 57: 551-554, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/44841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">44841</a>] [<a href="https://doi.org/10.1038/icb.1979.56" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="44841">van de Water et al. (1979)</a> but was not propagated. <a href="#113" class="mim-tip-reference" title="Tybulewicz, V. L. J., Tremblay, M. L., LaMarca, M. E., Willemsen, R., Stubblefield, B. K., Winfield, S., Zablocka, B., Sidransky, E., Martin, B. M., Huang, S. P., Mintzer, K. A., Westphal, H., Mulligan, R. C., Ginns, E. I. <strong>Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene.</strong> Nature 357: 407-410, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1594045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1594045</a>] [<a href="https://doi.org/10.1038/357407a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1594045">Tybulewicz et al. (1992)</a> produced a murine model by targeted disruption of the mouse Gba gene. A null allele was created in embryonic stem cells, and the genetically modified cells were used to establish a mouse strain carrying the mutation. Mice homozygous for the mutation had less than 4% of normal glucocerebrosidase activity, died within 24 hours of birth, and stored glucocerebroside in lysosomes of cells of the reticuloendothelial system. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=44841+1594045" 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>To produce mice with point mutations that correspond to the clinical types of Gaucher disease, <a href="#66" class="mim-tip-reference" title="Liu, Y., Suzuki, K., Reed, J. D., Grinberg, A., Westphal, H., Hoffmann, A., Doring, T., Sandhoff, K., Proia, R. L. <strong>Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure (SIMP).</strong> Proc. Nat. Acad. Sci. 95: 2503-2508, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9482915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9482915</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9482915[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/10.1073/pnas.95.5.2503" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9482915">Liu et al. (1998)</a> devised a highly efficient 1-step mutagenesis method, called the single insertion mutagenesis procedure (SIMP), to introduce human disease mutations into the mouse Gba gene. By use of SIMP, they generated mice carrying either the very severe triply mutant allele (<a href="#0009">606463.0009</a>) that can cause type II disease or the less severe L444P mutation associated with type III disease. Mice homozygous for the triple mutation had little GBA enzyme activity and accumulated glucosylceramide in brain and liver. In contrast, the mice homozygous for the L444P mutation had higher levels of GBA activity and no detectable accumulation of glucosylceramide in brain and liver. Surprisingly, both point mutation mice died within 48 hours of birth, apparently of a compromised epidermal permeability barrier caused by defective glucosylceramide metabolism in the epidermis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9482915" 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="#27" class="mim-tip-reference" title="Enquist, I. B., Lo Bianco, C., Ooka, A., Nilsson, E., Mansson, J.-E., Ehinger, M., Richter, J., Brady, R. O., Kirik, D., Karlsson, S. <strong>Murine models of acute neuronopathic Gaucher disease.</strong> Proc. Nat. Acad. Sci. 104: 17483-17488, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17954912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17954912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17954912[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/10.1073/pnas.0708086104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17954912">Enquist et al. (2007)</a> generated transgenic mice with targeted disruption of the Gba gene, but low expression of the gene in skin to prevent early lethality. The mice showed a phenotype similar to the severe neuronopathic form of Gaucher disease, including rapid motor dysfunction, seizures, and hyperextension of the neck associated with severe neurodegeneration and apoptotic neuronal cell death. Some neurons had large vacuoles indicating neuronal lipid accumulation. A second mouse model with Gba deficiency restricted to neural and glial cell progenitors demonstrated a similar neuropathology as the first mouse model, but with a delayed onset and slower disease progression. These findings indicated that Gba deficiency within microglial cells of hematopoietic origin is not the primary determinant of the CNS pathology, but may influence disease progression. The findings also showed that normal hematopoietic-derived microglial cells could not rescue the neurodegenerative phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17954912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="/allelicVariants/606463" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606463[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 GAUCHER DISEASE, TYPE II</strong>
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GAUCHER DISEASE, TYPE III, INCLUDED<br />
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GAUCHER DISEASE, TYPE I, INCLUDED<br />
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PARKINSON DISEASE, LATE-ONSET, SUSCEPTIBILITY TO, INCLUDED<br />
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DEMENTIA, LEWY BODY, SUSCEPTIBILITY TO, INCLUDED
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GBA, LEU444PRO
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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> rs421016 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs421016;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/rs421016?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=rs421016" 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=rs421016" 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=RCV000004509 OR RCV000004510 OR RCV000004511 OR RCV000004512 OR RCV000004513 OR RCV000004533 OR RCV000004534 OR RCV000004535 OR RCV000004536 OR RCV000020150 OR RCV000225393 OR RCV000225500 OR RCV000413257 OR RCV000626625 OR RCV001004112 OR RCV001197164 OR RCV001781179 OR RCV001836696 OR RCV002476924 OR RCV003398445 OR RCV003987311 OR RCV004018555" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004509, RCV000004510, RCV000004511, RCV000004512, RCV000004513, RCV000004533, RCV000004534, RCV000004535, RCV000004536, RCV000020150, RCV000225393, RCV000225500, RCV000413257, RCV000626625, RCV001004112, RCV001197164, RCV001781179, RCV001836696, RCV002476924, RCV003398445, RCV003987311, RCV004018555" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004509...</a>
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<p>The leu444-to-pro (L444P) substitution in exon 10 of the GBA gene has been reported as resulting from a 1448T-C transition (<a href="#125" class="mim-tip-reference" title="Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E. <strong>Prediction of severity of Gaucher's disease by identification of mutations at DNA level.</strong> Lancet 334: 349-352, 1989. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569551</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)90536-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2569551">Zimran et al., 1989</a>) and from a 6433T-C transition (<a href="#65" class="mim-tip-reference" title="Latham, T., Grabowski, G. A., Theophilus, B. D. M., Smith, F. I. <strong>Complex alleles of the acid beta-glucosidase gene in Gaucher disease.</strong> Am. J. Hum. Genet. 47: 79-86, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349952</a>]" pmid="2349952">Latham et al., 1990</a>), depending upon the reference sequence cited. This mutation has alternatively been referred to as LEU483PRO (<a href="#88" class="mim-tip-reference" title="Saranjam, H., Chopra, S. S., Levy, H., Stubblefield, B. K., Maniwang, E., Cohen, I. J., Baris, H., Sidransky, E., Tayebi, N. <strong>A germline or de novo mutation in two families with Gaucher disease: implications for recessive disorders.</strong> Europ. J. Hum. Genet. 21: 115-117, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22713811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22713811</a>] [<a href="https://doi.org/10.1038/ejhg.2012.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22713811">Saranjam et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2349952+2569551+22713811" 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="#82" class="mim-tip-reference" title="Reczek, D., Schwake, M., Schroder, J., Hughes, H., Blanz, J., Jin, X., Brondyk, W., Van Patten, S., Edmunds, T., Saftig, P. <strong>LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase.</strong> Cell 131: 770-783, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18022370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18022370</a>] [<a href="https://doi.org/10.1016/j.cell.2007.10.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18022370">Reczek et al. (2007)</a> stated that the L444P mutation results in retention of GBA in the ER. They found that overexpression of the human GBA receptor, LIMP2 (SCARB2; <a href="/entry/602257">602257</a>), in mouse embryonic fibroblasts rescued lysosomal targeting of GBA with the L444P mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18022370" 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>Gaucher Disease</em></strong></p><p>
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<a href="#110" class="mim-tip-reference" title="Tsuji, S., Choudary, P. V., Martin, B. M., Stubblefield, B. K., Mayor, J. A., Barranger, J. A., Ginns, E. I. <strong>A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease.</strong> New Eng. J. Med. 316: 570-575, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2880291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2880291</a>] [<a href="https://doi.org/10.1056/NEJM198703053161002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2880291">Tsuji et al. (1987)</a> identified the L444P substitution in the GBA gene in patients with Gaucher disease types I (<a href="/entry/230800">230800</a>), II (<a href="/entry/230900">230900</a>), and III (<a href="/entry/231000">231000</a>). Two of the 5 patients with type II and 7 of the 11 with type III were homozygous for this mutation, whereas 4 of 20 patients with type I Gaucher disease had this mutant allele in heterozygous state. The mutant allele was not found in 29 normal controls. The L444P substitution occurs naturally in the GBA pseudogene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2880291" 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="#120" class="mim-tip-reference" title="Wigderson, M., Firon, N., Horowitz, Z., Wilder, S., Frishberg, Y., Reiner, O., Horowitz, M. <strong>Characterization of mutations in Gaucher patients by cDNA cloning.</strong> Am. J. Hum. Genet. 44: 365-377, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2464926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2464926</a>]" pmid="2464926">Wigderson et al. (1989)</a> identified the L444P mutation in patients with type I, type II, and type III disease. One patient with type II disease was compound heterozygous for L444P and P415R (<a href="#0002">606463.0002</a>). <a href="#32" class="mim-tip-reference" title="Firon, N., Eyal, N., Kolodny, E. H., Horowitz, M. <strong>Genotype assignment in Gaucher disease by selective amplification of the active glucocerebrosidase gene.</strong> Am. J. Hum. Genet. 46: 527-532, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309702</a>]" pmid="2309702">Firon et al. (1990)</a> found the L444P mutation in both Ashkenazi Jewish and non-Jewish patients with type I Gaucher disease, but only homozygotes with this mutation had the neurologic forms type II or III. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2464926+2309702" 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="#21" class="mim-tip-reference" title="Dahl, N., Lagerstrom, M., Erikson, A., Pettersson, U. <strong>Gaucher disease type III (Norrbottnian type) is caused by a single mutation in exon 10 of the glucocerebrosidase gene.</strong> Am. J. Hum. Genet. 47: 275-278, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2378352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2378352</a>]" pmid="2378352">Dahl et al. (1990)</a> found that the Norrbottnian form of Gaucher disease (type III) in Sweden is caused by the L444P mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2378352" 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 3 patients with type I and 1 patient with type II Gaucher disease, <a href="#48" class="mim-tip-reference" title="Hong, C. M., Ohashi, T., Yu, X. J., Weiler, S., Barranger, J. A. <strong>Sequence of two alleles responsible for Gaucher disease.</strong> DNA Cell Biol. 9: 233-241, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1972019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1972019</a>] [<a href="https://doi.org/10.1089/dna.1990.9.233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1972019">Hong et al. (1990)</a> identified a complex allele with 3 point mutations in the GBA gene (<a href="#0009">606463.0009</a>), 1 of which was L444P. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1972019" 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="#62" class="mim-tip-reference" title="Koprivica, V., Stone, D. L., Park, J. K., Callahan, M., Frisch, A., Cohen, I. J., Tayebi, N., Sidransky, E. <strong>Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease.</strong> Am. J. Hum. Genet. 66: 1777-1786, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10796875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10796875</a>] [<a href="https://doi.org/10.1086/302925" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10796875">Koprivica et al. (2000)</a> found that homozygosity for L444P was associated with type III Gaucher disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10796875" 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="#88" class="mim-tip-reference" title="Saranjam, H., Chopra, S. S., Levy, H., Stubblefield, B. K., Maniwang, E., Cohen, I. J., Baris, H., Sidransky, E., Tayebi, N. <strong>A germline or de novo mutation in two families with Gaucher disease: implications for recessive disorders.</strong> Europ. J. Hum. Genet. 21: 115-117, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22713811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22713811</a>] [<a href="https://doi.org/10.1038/ejhg.2012.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22713811">Saranjam et al. (2013)</a> reported 2 unrelated infants with severe, lethal type II Gaucher disease who were compound heterozygous for 2 mutations in the GBA gene, one of which was L444P. While the other mutation was identified in the paternal line of each patient (see, e.g., T323I, <a href="#0017">606463.0017</a>), the L444P allele was not detected in DNA samples from either patient's mother, suggesting that it occurred either as a result of germline mosaicism or as a de novo mutation in 1 ovum that took place during cell division. The findings had implications for genetic counseling, in that even if only 1 parent is found to be a carrier for a recessive disorder, the chance of having an affected child may not be zero. <a href="#88" class="mim-tip-reference" title="Saranjam, H., Chopra, S. S., Levy, H., Stubblefield, B. K., Maniwang, E., Cohen, I. J., Baris, H., Sidransky, E., Tayebi, N. <strong>A germline or de novo mutation in two families with Gaucher disease: implications for recessive disorders.</strong> Europ. J. Hum. Genet. 21: 115-117, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22713811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22713811</a>] [<a href="https://doi.org/10.1038/ejhg.2012.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22713811">Saranjam et al. (2013)</a> noted that the L444P change occurs at a known mutational hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22713811" 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</em></strong></p><p>
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<a href="#103" class="mim-tip-reference" title="Tan, E.-K., Tong, J., Fook-Chong, S., Yih, Y., Wong, M.-C., Pavanni, R., Zhao, Y. <strong>Glucocerebrosidase mutations and risk of Parkinson disease in Chinese patients.</strong> Arch. Neurol. 64: 1056-1058, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17620502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17620502</a>] [<a href="https://doi.org/10.1001/archneur.64.7.1056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17620502">Tan et al. (2007)</a> identified a heterozygous L444P mutation in 8 (2.4%) of 331 Chinese patients with typical Parkinson disease (<a href="/entry/168600">168600</a>) and none of 347 controls. The age at onset was lower and the percentage of women higher in patients with the L444P mutation compared to those without the mutation. <a href="#103" class="mim-tip-reference" title="Tan, E.-K., Tong, J., Fook-Chong, S., Yih, Y., Wong, M.-C., Pavanni, R., Zhao, Y. <strong>Glucocerebrosidase mutations and risk of Parkinson disease in Chinese patients.</strong> Arch. Neurol. 64: 1056-1058, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17620502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17620502</a>] [<a href="https://doi.org/10.1001/archneur.64.7.1056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17620502">Tan et al. (2007)</a> noted that the findings were significant because Gaucher disease is extremely rare among the Chinese. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17620502" 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="#45" class="mim-tip-reference" title="Gutti, U., Fung, H.-C., Hruska, K. S., LaMarca, M. E., Chen, C.-M., Wu, Y.-R., Sidransky, E. <strong>The need for appropriate genotyping strategies for glucocerebrosidase mutations in cohorts with Parkinson disease. (Letter)</strong> Arch. Neurol. 65: 850-851, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18541817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18541817</a>] [<a href="https://doi.org/10.1001/archneur.65.6.850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18541817">Gutti et al. (2008)</a> identified the L444P mutation in 4 (2.2%) of 184 Taiwanese patients with PD. Six other GBA variants were identified in 1 patient each, yielding a total of 7 different mutations in 10 patients (5.4%). <a href="#45" class="mim-tip-reference" title="Gutti, U., Fung, H.-C., Hruska, K. S., LaMarca, M. E., Chen, C.-M., Wu, Y.-R., Sidransky, E. <strong>The need for appropriate genotyping strategies for glucocerebrosidase mutations in cohorts with Parkinson disease. (Letter)</strong> Arch. Neurol. 65: 850-851, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18541817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18541817</a>] [<a href="https://doi.org/10.1001/archneur.65.6.850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18541817">Gutti et al. (2008)</a> suggested that sequencing the entire GBA gene would reveal additional variant that may contribute to PD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18541817" 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="#74" class="mim-tip-reference" title="Neumann, J., Bras, J., Deas, E., O'Sullivan, S. S., Parkkinen, L., Lachmann, R. H., Li, A., Holton, J., Guerreiro, R., Paudel, R., Segarane, B., Singleton, A., Lees, A., Hardy, J., Houlden, H., Revesz, T., Wood, N. W. <strong>Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.</strong> Brain 132: 1783-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286695</a>] [<a href="https://doi.org/10.1093/brain/awp044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19286695">Neumann et al. (2009)</a> identified a heterozygous L444P mutation in 11 (1.39%) of 790 British patients with PD, which was not found in 257 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19286695" 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="#39" class="mim-tip-reference" title="Gonzalez-del Rincon, M. de L., Monroy Jaramillo, N., Suarez Martinez, A. I., Yescas Gomez, P., Boll Woehrlen, M. C., Lopez Lopez, M., Alonso Vilatela, M. E. <strong>The L444P GBA mutation is associated with early-onset Parkinson's disease in Mexican Mestizos. (Letter)</strong> Clin. Genet. 84: 386-387, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23448517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23448517</a>] [<a href="https://doi.org/10.1111/cge.12084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23448517">Gonzalez-del Rincon et al. (2013)</a> identified a heterozygous L444P mutation in 7 (5.5%) of 128 Mexican Mestizo patients with early-onset PD (before 45 yeras of age) and in none (0%) of 252 ethnically matched controls. Six (85.7%) of the 7 patients had psychiatric symptoms, including major depressive disorder, generalized anxiety disorder, and obsessive compulsive disorder, which was significantly higher than the prevalence of these disorders in controls (24.7%). In addition, 57% of mutation carriers presented with cognitive decline compared to 5.7% of controls. <a href="#39" class="mim-tip-reference" title="Gonzalez-del Rincon, M. de L., Monroy Jaramillo, N., Suarez Martinez, A. I., Yescas Gomez, P., Boll Woehrlen, M. C., Lopez Lopez, M., Alonso Vilatela, M. E. <strong>The L444P GBA mutation is associated with early-onset Parkinson's disease in Mexican Mestizos. (Letter)</strong> Clin. Genet. 84: 386-387, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23448517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23448517</a>] [<a href="https://doi.org/10.1111/cge.12084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23448517">Gonzalez-del Rincon et al. (2013)</a> concluded that the risk for PD conferred by GBA mutations may be higher than previously thought, and that GBA-associated PD may predispose to psychiatric symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23448517" 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>Lewy Body Dementia</em></strong></p><p>
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<a href="#67" class="mim-tip-reference" title="Mata, I. F., Samii, A., Schneer, S. H., Roberts, J. W., Griffith, A., Leis, B. C., Schellenberg, G. D., Sidransky, E., Bird, T. D., Leverenz, J. B., Tsuang, D., Zabetian, C. P. <strong>Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.</strong> Arch. Neurol. 65: 379-382, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18332251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18332251</a>] [<a href="https://doi.org/10.1001/archneurol.2007.68" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18332251">Mata et al. (2008)</a> identified heterozygosity for the L444P mutation in 10 (1.4%) of 721 PD patients, 1 (1.8%) of 57 patients with Lewy body dementia (DLB; <a href="/entry/127750">127750</a>), and 0 of 554 control individuals, all of European origin. <a href="#67" class="mim-tip-reference" title="Mata, I. F., Samii, A., Schneer, S. H., Roberts, J. W., Griffith, A., Leis, B. C., Schellenberg, G. D., Sidransky, E., Bird, T. D., Leverenz, J. B., Tsuang, D., Zabetian, C. P. <strong>Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.</strong> Arch. Neurol. 65: 379-382, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18332251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18332251</a>] [<a href="https://doi.org/10.1001/archneurol.2007.68" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18332251">Mata et al. (2008)</a> estimated that the population-attributable risk for GBA mutations in Lewy body disorders was only about 3% in patients of European ancestry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18332251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient with Gaucher disease type II (<a href="/entry/230900">230900</a>), <a href="#120" class="mim-tip-reference" title="Wigderson, M., Firon, N., Horowitz, Z., Wilder, S., Frishberg, Y., Reiner, O., Horowitz, M. <strong>Characterization of mutations in Gaucher patients by cDNA cloning.</strong> Am. J. Hum. Genet. 44: 365-377, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2464926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2464926</a>]" pmid="2464926">Wigderson et al. (1989)</a> identified compound heterozygosity for 2 mutations in the GBA gene: a 5976C-G transversion, resulting in a pro415-to-arg (P415R) substitution, and L444P (<a href="#0001">606463.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2464926" 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="#82" class="mim-tip-reference" title="Reczek, D., Schwake, M., Schroder, J., Hughes, H., Blanz, J., Jin, X., Brondyk, W., Van Patten, S., Edmunds, T., Saftig, P. <strong>LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase.</strong> Cell 131: 770-783, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18022370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18022370</a>] [<a href="https://doi.org/10.1016/j.cell.2007.10.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18022370">Reczek et al. (2007)</a> found that GBA with the P415R mutation was retained in the ER of transfected mouse embryonic fibroblasts. Overexpression of the GBA receptor, LIMP2 (SCARB2; <a href="/entry/602257">602257</a>), did not rescue lysosomal targeting of GBA with the P415R mutation, suggesting that this mutation directly or indirectly interferes with interaction between GBA and LIMP2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18022370" 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> rs76763715 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs76763715;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/rs76763715?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=rs76763715" 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=rs76763715" 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=RCV000004515 OR RCV000004516 OR RCV000004517 OR RCV000079336 OR RCV000396221 OR RCV000414782 OR RCV000515439 OR RCV001004117 OR RCV001195689 OR RCV001197918 OR RCV001270528 OR RCV002247244 OR RCV003982824 OR RCV004018556 OR RCV004555830" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004515, RCV000004516, RCV000004517, RCV000079336, RCV000396221, RCV000414782, RCV000515439, RCV001004117, RCV001195689, RCV001197918, RCV001270528, RCV002247244, RCV003982824, RCV004018556, RCV004555830" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004515...</a>
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<p><strong><em>Gaucher Disease</em></strong></p><p>
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The asn370-to-ser (N370S) substitution in exon 9 of the GBA gene has been reported as resulting from a 5841A-G transition (<a href="#65" class="mim-tip-reference" title="Latham, T., Grabowski, G. A., Theophilus, B. D. M., Smith, F. I. <strong>Complex alleles of the acid beta-glucosidase gene in Gaucher disease.</strong> Am. J. Hum. Genet. 47: 79-86, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349952</a>]" pmid="2349952">Latham et al., 1990</a>) and from a 1226A-G transition (<a href="#112" class="mim-tip-reference" title="Tsuji, S., Martin, B. M., Barranger, J. A., Stubblefield, B. K., LaMarca, M. E., Ginns, E. I. <strong>Genetic heterogeneity in type I Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals.</strong> Proc. Nat. Acad. Sci. 85: 2349-2352, 1988. Note: Erratum: Proc. Nat. Acad. Sci. 85: 5708 only, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3353383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3353383</a>] [<a href="https://doi.org/10.1073/pnas.85.7.2349" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3353383">Tsuji et al., 1988</a>), depending upon the reference sequence cited. It is the most common Gaucher disease allele in the Ashkenazi Jewish population and is only associated with the nonneuronopathic type I form of Gaucher disease (<a href="/entry/230800">230800</a>) (<a href="#125" class="mim-tip-reference" title="Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E. <strong>Prediction of severity of Gaucher's disease by identification of mutations at DNA level.</strong> Lancet 334: 349-352, 1989. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569551</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)90536-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2569551">Zimran et al., 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3353383+2349952+2569551" 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="#112" class="mim-tip-reference" title="Tsuji, S., Martin, B. M., Barranger, J. A., Stubblefield, B. K., LaMarca, M. E., Ginns, E. I. <strong>Genetic heterogeneity in type I Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals.</strong> Proc. Nat. Acad. Sci. 85: 2349-2352, 1988. Note: Erratum: Proc. Nat. Acad. Sci. 85: 5708 only, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3353383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3353383</a>] [<a href="https://doi.org/10.1073/pnas.85.7.2349" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3353383">Tsuji et al. (1988)</a> identified the N370S substitution in an Ashkenazi Jewish patient with type I Gaucher disease. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation occurs exclusively with the type I phenotype. None of 6 type II (<a href="/entry/230900">230900</a>) patients, 11 type III (<a href="/entry/231000">231000</a>) patients, or 12 normal controls had this allele. In contrast, 15 of 24 type I patients had 1 allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazi Jewish type I patients had only 1 allele with this mutation, suggesting allelic heterogeneity even in this population. One patient with type I disease was compound heterozygous for N370S and L444P (<a href="#0001">606463.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3353383" 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="#125" class="mim-tip-reference" title="Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E. <strong>Prediction of severity of Gaucher's disease by identification of mutations at DNA level.</strong> Lancet 334: 349-352, 1989. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569551</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)90536-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2569551">Zimran et al. (1989)</a> found that the N370S substitution was associated with a mild clinical phenotype compared to L444P. Eight of 22 patients homozygous for N370S were entirely symptom-free. In symptomatic patients, the clinical features of the N370S homozygotes were usually related to splenomegaly and thrombocytopenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2569551" 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>Kolodny et al. (<a href="#60" class="mim-tip-reference" title="Kolodny, E., Firon, N., Natowicz, M., Horowitz, M. <strong>Gaucher disease in three successive generations of an Ashkenazi Jewish family: analysis of intrafamilial clinical variability by molecular diagnosis. (Abstract)</strong> Am. J. Hum. Genet. 45 (suppl.): A202 only, 1989."None>1989</a>, <a href="#61" class="mim-tip-reference" title="Kolodny, E. H., Firon, N., Eyal, N., Horowitz, M. <strong>Mutation analysis of an Ashkenazi Jewish family with Gaucher disease in three successive generations.</strong> Am. J. Med. Genet. 36: 467-472, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2117855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2117855</a>] [<a href="https://doi.org/10.1002/ajmg.1320360419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2117855">1990</a>) studied an unusual Ashkenazi Jewish family with affected members in 3 successive generations. Both N370S and L444P segregated in the family; 4 affected individuals were homozygous for N370S mutation, while 3 others were compound heterozygotes for the 2 mutations. Clinical severity was more marked in compound heterozygotes than in homozygotes. <a href="#32" class="mim-tip-reference" title="Firon, N., Eyal, N., Kolodny, E. H., Horowitz, M. <strong>Genotype assignment in Gaucher disease by selective amplification of the active glucocerebrosidase gene.</strong> Am. J. Hum. Genet. 46: 527-532, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309702</a>]" pmid="2309702">Firon et al. (1990)</a> found the N370S mutation in type I patients only. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2117855+2309702" 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="#123" class="mim-tip-reference" title="Zimran, A., Gelbart, T., Beutler, E. <strong>Linkage of the PvuII polymorphism with the common Jewish mutation for Gaucher disease.</strong> Am. J. Hum. Genet. 46: 902-905, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1971142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1971142</a>]" pmid="1971142">Zimran et al. (1990)</a> identified a 3931G-A polymorphism in intron 6 of the GBA gene, termed PvuII. Analysis of 54 unrelated Jewish Gaucher patients showed strong linkage disequilibrium between the negative polymorphism genotype and the common Jewish N370S mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1971142" 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>Among 593 unrelated normal Ashkenazi Jewish individuals, <a href="#124" class="mim-tip-reference" title="Zimran, A., Gelbart, T., Westwood, B., Grabowski, G. A., Beutler, E. <strong>High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews.</strong> Am. J. Hum. Genet. 49: 855-859, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1897529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1897529</a>]" pmid="1897529">Zimran et al. (1991)</a> identified 37 heterozygotes and 2 homozygotes for the N370S mutation, yielding an allele frequency of 0.035. Among 1,528 Ashkenazi Jewish individuals, <a href="#10" class="mim-tip-reference" title="Beutler, E., Gelbart, T., West, C. <strong>Identification of six new Gaucher disease mutations.</strong> Genomics 15: 203-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432537</a>] [<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432537">Beutler et al. (1993)</a> identified 87 heterozygotes and 4 homozygotes for N370S, yielding a frequency of 0.0311; pooling with data reported by <a href="#124" class="mim-tip-reference" title="Zimran, A., Gelbart, T., Westwood, B., Grabowski, G. A., Beutler, E. <strong>High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews.</strong> Am. J. Hum. Genet. 49: 855-859, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1897529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1897529</a>]" pmid="1897529">Zimran et al. (1991)</a> yielded a frequency of 0.032 for the N370S allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1897529+8432537" 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="#72" class="mim-tip-reference" title="Mistry, P. K., Smith, S. J., Ali, M., Hatton, C. S. R., McIntyre, N., Cox, T. M. <strong>Genetic diagnosis of Gaucher's disease.</strong> Lancet 339: 889-892, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348297</a>] [<a href="https://doi.org/10.1016/0140-6736(92)90928-v" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1348297">Mistry et al. (1992)</a> used the amplification refractory mutation system (ARMS) for direct detection of GBA mutations in Gaucher disease. PCR primers were designed to discriminate between mutant and wildtype alleles and to allow separation from products of the related pseudogene. The N370S mutation and a 2-bp insertion (84insGG; <a href="#0014">606463.0014</a>) were found exclusively in 5 patients of Ashkenazi Jewish descent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1348297" 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="#117" class="mim-tip-reference" title="van Weely, S., van den Berg, M., Barranger, J. A., Sa Miranda, M. C., Tager, J. M., Aerts, J. M. F. G. <strong>Role of pH in determining the cell-type-specific residual activity of glucocerebrosidase in type 1 Gaucher disease.</strong> J. Clin. Invest. 91: 1167-1175, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8450045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8450045</a>] [<a href="https://doi.org/10.1172/JCI116276" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8450045">Van Weely et al. (1993)</a> studied the properties of control and N370S mutant GBA in vitro and in vivo. The results indicated that the intralysosomal pH in the intact cell has a critical influence on the activation state of N370S GBA and its ability to hydrolyze substrate. This phenomenon may partly explain the clinical heterogeneity in patients with Gaucher disease caused by the N370S mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8450045" 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="#118" class="mim-tip-reference" title="Walley, A. J., Barth, M. L., Ellis, I., Fensom, A. H., Harris, A. <strong>Gaucher's disease in the United Kingdom: screening non-Jewish patients for the two common mutations.</strong> J. Med. Genet. 30: 280-283, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8487270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8487270</a>] [<a href="https://doi.org/10.1136/jmg.30.4.280" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8487270">Walley et al. (1993)</a> found that the N370S mutation accounted for 26% of Gaucher disease alleles among non-Jewish patients in the United Kingdom (total alleles = 54). They found a correlation between the presence of at least 1 N370S allele and mild disease. The L444P mutation accounted for 35% of the alleles and the remaining 39% were rare or undefined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8487270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The N370S mutation and the 84insGG mutation reportedly account for approximately 70% and 10%, respectively, of mutations in the Jewish population. <a href="#53" class="mim-tip-reference" title="Ida, H., Iwasawa, K., Kawame, H., Rennert, O. M., Maekawa, K., Eto, Y. <strong>Characteristics of gene mutations among 32 unrelated Japanese Gaucher disease patients: absence of the common Jewish 84GG and 1226G mutations.</strong> Hum. Genet. 95: 717-720, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789963</a>] [<a href="https://doi.org/10.1007/BF00209497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789963">Ida et al. (1995)</a> found neither mutation in 32 unrelated Japanese Gaucher patients, of whom 20 were type I, 6 were type II, and 6 were type III. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789963" 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="#18" class="mim-tip-reference" title="Cormand, B., Grinberg, D., Gort, L., Chabas, A., Vilageliu, L. <strong>Molecular analysis and clinical findings in the Spanish Gaucher disease population: putative haplotype of the N370S ancestral chromosome.</strong> Hum. Mutat. 11: 295-305, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554746</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<295::AID-HUMU7>3.0.CO;2-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9554746">Cormand et al. (1998)</a> found that N370S and L444P accounted for 66.1% of Gaucher disease alleles in Spain. Linkage disequilibrium was detected between these 2 mutations and an intragenic polymorphism, indicating that expansion of founder alleles occurred in both cases. Analysis of several microsatellite markers close to the GBA gene allowed them to establish a putative haplotype of the ancestral N370S chromosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554746" 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="#62" class="mim-tip-reference" title="Koprivica, V., Stone, D. L., Park, J. K., Callahan, M., Frisch, A., Cohen, I. J., Tayebi, N., Sidransky, E. <strong>Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease.</strong> Am. J. Hum. Genet. 66: 1777-1786, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10796875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10796875</a>] [<a href="https://doi.org/10.1086/302925" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10796875">Koprivica et al. (2000)</a> found that homozygosity or heterozygosity for N370S resulted in type I Gaucher disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10796875" 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="#24" class="mim-tip-reference" title="Dimitriou, E., Moraitou, M., Troungos, C., Schulpis, K., Michelakakis, H. <strong>Gaucher disease: frequency of the N370S mutation in the Greek population. (Letter)</strong> Clin. Genet. 78: 195-196, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20662857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20662857</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01381.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20662857">Dimitriou et al. (2010)</a> determined that the frequency of the N370S allele is 0.0046 in the Greek population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20662857" 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 and Lewy Body Dementia</em></strong></p><p>
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<a href="#67" class="mim-tip-reference" title="Mata, I. F., Samii, A., Schneer, S. H., Roberts, J. W., Griffith, A., Leis, B. C., Schellenberg, G. D., Sidransky, E., Bird, T. D., Leverenz, J. B., Tsuang, D., Zabetian, C. P. <strong>Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.</strong> Arch. Neurol. 65: 379-382, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18332251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18332251</a>] [<a href="https://doi.org/10.1001/archneurol.2007.68" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18332251">Mata et al. (2008)</a> identified heterozygosity for the N370S mutation in 11 (1.5%) of 721 patients with Parkinson disease (PD; <a href="/entry/168600">168600</a>), 1 (1.8%) of 57 patients with Lewy body dementia (DLB; <a href="/entry/127750">127750</a>), and 2 (0.4%) of 554 control individuals. All individuals were of European origin. <a href="#67" class="mim-tip-reference" title="Mata, I. F., Samii, A., Schneer, S. H., Roberts, J. W., Griffith, A., Leis, B. C., Schellenberg, G. D., Sidransky, E., Bird, T. D., Leverenz, J. B., Tsuang, D., Zabetian, C. P. <strong>Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.</strong> Arch. Neurol. 65: 379-382, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18332251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18332251</a>] [<a href="https://doi.org/10.1001/archneurol.2007.68" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18332251">Mata et al. (2008)</a> estimated that the population-attributable risk for GBA mutations in Lewy body disorders was only about 3% in patients of European ancestry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18332251" 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="#74" class="mim-tip-reference" title="Neumann, J., Bras, J., Deas, E., O'Sullivan, S. S., Parkkinen, L., Lachmann, R. H., Li, A., Holton, J., Guerreiro, R., Paudel, R., Segarane, B., Singleton, A., Lees, A., Hardy, J., Houlden, H., Revesz, T., Wood, N. W. <strong>Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.</strong> Brain 132: 1783-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286695</a>] [<a href="https://doi.org/10.1093/brain/awp044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19286695">Neumann et al. (2009)</a> identified a heterozygous N370S mutation in 8 (1.01%) of 790 British patients with PD and in 1 (0.39%) of 257 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19286695" 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 GAUCHER DISEASE, TYPE I</strong>
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GBA, ARG119GLN
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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> rs79653797 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs79653797;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/rs79653797?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=rs79653797" 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=rs79653797" 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=RCV000004518 OR RCV000004519 OR RCV000020154 OR RCV001250522 OR RCV001781178" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004518, RCV000004519, RCV000020154, RCV001250522, RCV001781178" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004518...</a>
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<p>The arg119-to-gln (R119Q) substitution in the GBA gene has been reported to result from a 3060G-A transition (<a href="#43" class="mim-tip-reference" title="Graves, P. N., Grabowski, G. A., Eisner, R., Palese, P., Smith, F. I. <strong>Gaucher disease type I: cloning and characterization of a cDNA encoding acid beta-glucosidase from an Ashkenazi Jewish patient.</strong> DNA 7: 521-528, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3180993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3180993</a>] [<a href="https://doi.org/10.1089/dna.1.1988.7.521" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3180993">Graves et al., 1988</a>) and a 476G-A transition (<a href="#30" class="mim-tip-reference" title="Felderhoff-Mueser, U., Uhl, J., Penzel, R., van Landeghem, F., Vogel, M., Obladen, M., Kopitz, J. <strong>Intrauterine onset of acute neuropathic type 2 Gaucher disease: identification of a novel insertion sequence.</strong> Am. J. Med. Genet. 128A: 138-143, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15214004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15214004</a>] [<a href="https://doi.org/10.1002/ajmg.a.20445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15214004">Felderhoff-Mueser et al., 2004</a>), depending upon the reference sequence cited. This mutation has also been referred to as ARG120GLN by others (<a href="#65" class="mim-tip-reference" title="Latham, T., Grabowski, G. A., Theophilus, B. D. M., Smith, F. I. <strong>Complex alleles of the acid beta-glucosidase gene in Gaucher disease.</strong> Am. J. Hum. Genet. 47: 79-86, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349952</a>]" pmid="2349952">Latham et al., 1990</a>; <a href="#30" class="mim-tip-reference" title="Felderhoff-Mueser, U., Uhl, J., Penzel, R., van Landeghem, F., Vogel, M., Obladen, M., Kopitz, J. <strong>Intrauterine onset of acute neuropathic type 2 Gaucher disease: identification of a novel insertion sequence.</strong> Am. J. Med. Genet. 128A: 138-143, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15214004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15214004</a>] [<a href="https://doi.org/10.1002/ajmg.a.20445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15214004">Felderhoff-Mueser et al., 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2349952+3180993+15214004" 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="#43" class="mim-tip-reference" title="Graves, P. N., Grabowski, G. A., Eisner, R., Palese, P., Smith, F. I. <strong>Gaucher disease type I: cloning and characterization of a cDNA encoding acid beta-glucosidase from an Ashkenazi Jewish patient.</strong> DNA 7: 521-528, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3180993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3180993</a>] [<a href="https://doi.org/10.1089/dna.1.1988.7.521" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3180993">Graves et al. (1988)</a> identified a heterozygous R119Q substitution in the GBA gene in 2 Ashkenazi Jewish cousins with Gaucher disease type I (<a href="/entry/230800">230800</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3180993" 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 premature infant with the perinatal lethal form of Gaucher disease (<a href="/entry/608013">608013</a>), <a href="#30" class="mim-tip-reference" title="Felderhoff-Mueser, U., Uhl, J., Penzel, R., van Landeghem, F., Vogel, M., Obladen, M., Kopitz, J. <strong>Intrauterine onset of acute neuropathic type 2 Gaucher disease: identification of a novel insertion sequence.</strong> Am. J. Med. Genet. 128A: 138-143, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15214004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15214004</a>] [<a href="https://doi.org/10.1002/ajmg.a.20445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15214004">Felderhoff-Mueser et al. (2004)</a> identified compound heterozygosity for the R120Q mutation and an IVS10-1G-A substitution (<a href="#0046">606463.0046</a>) in the GBA gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15214004" 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> rs80356769 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356769;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/rs80356769?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=rs80356769" 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=rs80356769" 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=RCV000004520 OR RCV000004521 OR RCV000020148 OR RCV000762854 OR RCV001004115 OR RCV001382044 OR RCV001836694" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004520, RCV000004521, RCV000020148, RCV000762854, RCV001004115, RCV001382044, RCV001836694" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004520...</a>
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<p><a href="#107" class="mim-tip-reference" title="Theophilus, B. D. M., Latham, T., Grabowski, G. A., Smith, F. I. <strong>Comparison of RNase A, a chemical cleavage and GC-clamped denaturing gradient gel electrophoresis for the detection of mutations in exon 9 of the human acid beta-glucosidase gene.</strong> Nucleic Acids Res. 17: 7707-7722, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2508065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2508065</a>] [<a href="https://doi.org/10.1093/nar/17.19.7707" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2508065">Theophilus et al. (1989)</a> and <a href="#65" class="mim-tip-reference" title="Latham, T., Grabowski, G. A., Theophilus, B. D. M., Smith, F. I. <strong>Complex alleles of the acid beta-glucosidase gene in Gaucher disease.</strong> Am. J. Hum. Genet. 47: 79-86, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349952</a>]" pmid="2349952">Latham et al. (1990)</a> identified a heterozygous 5912G-T transversion in the GBA gene, resulting in a val394-to-leu (V394L) substitution, in an Ashkenazi Jewish/Irish patient with Gaucher disease type III (<a href="/entry/231000">231000</a>) and an Ashkenazi Jewish patient with Gaucher disease type I (<a href="/entry/230800">230800</a>). The patient with type III disease was compound heterozygous for the V394L substitution on 1 allele and a complex substitution (<a href="#0009">606463.0009</a>) and D409H (<a href="#0006">606463.0006</a>) on the other allele. He developed psychomotor retardation and myoclonic seizures by age 5 years and died at 6 years. The patient with type I disease was compound heterozygous for V394L and N370S (<a href="#0003">606463.0003</a>). <a href="#65" class="mim-tip-reference" title="Latham, T., Grabowski, G. A., Theophilus, B. D. M., Smith, F. I. <strong>Complex alleles of the acid beta-glucosidase gene in Gaucher disease.</strong> Am. J. Hum. Genet. 47: 79-86, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349952</a>]" pmid="2349952">Latham et al. (1990)</a> suggested that the N370S allele protected the type I patient from the development of neuronopathic disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2349952+2508065" 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> rs1064651 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1064651;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/rs1064651?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=rs1064651" 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=rs1064651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs77369218 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs77369218;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=rs77369218" 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=rs77369218" 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=RCV000004522 OR RCV000004523 OR RCV000004524 OR RCV000004525 OR RCV000004526 OR RCV000004580 OR RCV000004581 OR RCV000055773 OR RCV000079338 OR RCV000762853 OR RCV001004114 OR RCV001836695 OR RCV004018557" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004522, RCV000004523, RCV000004524, RCV000004525, RCV000004526, RCV000004580, RCV000004581, RCV000055773, RCV000079338, RCV000762853, RCV001004114, RCV001836695, RCV004018557" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004522...</a>
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<p><a href="#63" class="mim-tip-reference" title="Kurolap, A., del Toro, M., Spiegel, R., Gutstein, A., Shafir, G., Cohen, I. J., Barrabes, J. A., Feldman, H. B. <strong>Gaucher disease type 3c: new patients with unique presentations and review of the literature.</strong> Molec. Genet. Metab. 127: 138-146, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31130326/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31130326</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.05.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31130326">Kurolap et al. (2019)</a> noted that the ASP409HIS mutation is annotated as ASP448HIS (D448H), resulting from a c.1342G-C transversion (c.1342G-C, NM_000157.3) in the GBA gene. The sequence includes the 39-residue signal peptide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31130326" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The asp409-to-his (D409H) substitution in exon 9 of the GBA gene has also been reported as resulting from a c.957G-C transversion, based on a different reference sequence (<a href="#13" class="mim-tip-reference" title="Beutler, E. <strong>Gaucher disease: new molecular approaches to diagnosis and treatment.</strong> Science 256: 794-799, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1589760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1589760</a>] [<a href="https://doi.org/10.1126/science.1589760" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1589760">Beutler, 1992</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1589760" 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="#107" class="mim-tip-reference" title="Theophilus, B. D. M., Latham, T., Grabowski, G. A., Smith, F. I. <strong>Comparison of RNase A, a chemical cleavage and GC-clamped denaturing gradient gel electrophoresis for the detection of mutations in exon 9 of the human acid beta-glucosidase gene.</strong> Nucleic Acids Res. 17: 7707-7722, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2508065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2508065</a>] [<a href="https://doi.org/10.1093/nar/17.19.7707" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2508065">Theophilus et al. (1989)</a> identified a heterozygous D409H mutation in the GBA gene in 2 patients with type I Gaucher disease (<a href="/entry/230800">230800</a>) and 1 patient with type III (<a href="/entry/231000">231000</a>) Gaucher disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2508065" 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="#20" class="mim-tip-reference" title="Cormand, B., Vilageliu, L., Burguera, J. M., Balcells, S., Gonzalez-Duarte, R., Grinberg, D., Chabas, A. <strong>Gaucher disease in Spanish patients: analysis of eight mutations.</strong> Hum. Mutat. 5: 303-309, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7627184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7627184</a>] [<a href="https://doi.org/10.1002/humu.1380050406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7627184">Cormand et al. (1995)</a> identified heterozygosity for the D409H allele in Spanish patients with types I, II (<a href="/entry/230900">230900</a>), and III Gaucher disease. All patients had markedly different clinical phenotypes. <a href="#20" class="mim-tip-reference" title="Cormand, B., Vilageliu, L., Burguera, J. M., Balcells, S., Gonzalez-Duarte, R., Grinberg, D., Chabas, A. <strong>Gaucher disease in Spanish patients: analysis of eight mutations.</strong> Hum. Mutat. 5: 303-309, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7627184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7627184</a>] [<a href="https://doi.org/10.1002/humu.1380050406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7627184">Cormand et al. (1995)</a> found that the D409H mutation accounted for 4 (5.7%) of 70 mutated alleles among 35 Spanish patients with Gaucher disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7627184" 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="#16" class="mim-tip-reference" title="Chabas, A., Cormand, B., Grinberg, D., Burguera, J. M., Balcells, S., Merino, J. L., Mate, I., Sobrino, J. A., Gonzalez-Duarte, R., Vilageliu, L. <strong>Unusual expression of Gaucher's disease: cardiovascular calcifications in three sibs homozygous for the D409H mutation.</strong> J. Med. Genet. 32: 740-742, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8544197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8544197</a>] [<a href="https://doi.org/10.1136/jmg.32.9.740" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8544197">Chabas et al. (1995)</a> described 3 Spanish sisters with an unusual form of Gaucher disease, later designated type IIIC (<a href="/entry/231005">231005</a>) (<a href="#15" class="mim-tip-reference" title="Bohlega, S., Kambouris, M., Shahid, M., Al Homsi, M., Al Sous, W. <strong>Gaucher disease with oculomotor apraxia and cardiovascular calcification (Gaucher type IIIC).</strong> Neurology 54: 261-263, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10636167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10636167</a>] [<a href="https://doi.org/10.1212/wnl.54.1.261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10636167">Bohlega et al., 2000</a>), due to a homozygous D409H substitution in the GBA gene. Hepatosplenomegaly was present in all 3 sibs; characteristic Gaucher cells were found on bone marrow aspirate in 2 and in the splenectomy specimen in the third. The patients had cardiovascular abnormalities consisting of calcification of the ascending aorta and of the aortic and mitral valves. Neurologic findings included ophthalmoplegia and saccadic eye movements in 2 of the sisters, and tonic-clonic seizures in the third. The 3 sisters died at ages 16, 15, and 13, 2 of them having undergone aortic valve replacement. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8544197+10636167" 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="#115" class="mim-tip-reference" title="Uyama, E., Uchino, M., Ida, H., Eto, Y., Owada, M. <strong>D409H/D409H genotype in Gaucher-like disease. (Letter)</strong> J. Med. Genet. 34: 175 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9040001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9040001</a>] [<a href="https://doi.org/10.1136/jmg.34.2.175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9040001">Uyama et al. (1997)</a> identified the homozygous D409H mutation in 3 Japanese adult sibs reported by <a href="#114" class="mim-tip-reference" title="Uyama, E., Takahashi, K., Owada, M., Okamura, R., Naito, M., Tsuji, S., Kawasaki, S., Araki, S. <strong>Hydrocephalus, corneal opacities, deafness, valvular heart disease, deformed toes and leptomeningeal fibrous thickening in adult siblings: a new syndrome associated with beta-glucocerebrosidase deficiency and a mosaic population of storage cells.</strong> Acta Neurol. Scand. 86: 407-420, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1333717/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1333717</a>] [<a href="https://doi.org/10.1111/j.1600-0404.1992.tb05109.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1333717">Uyama et al. (1992)</a> who had Gaucher disease associated with supranuclear ophthalmoplegia and cardiovascular calcifications. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1333717+9040001" 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>Homozygosity for the D409H mutation has been reported in Arab (<a href="#1" class="mim-tip-reference" title="Abrahamov, A., Elstein, D., Gross-Tsur, V., Farber, B., Glaser, Y., Hadas-Halpern, I., Ronen, S., Tafakjdi, M., Horowitz, M., Zimram, A. <strong>Gaucher's disease variant characterized by progressive calcification of heart valves and unique genotype.</strong> Lancet 346: 1000-1003, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7475546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7475546</a>] [<a href="https://doi.org/10.1016/s0140-6736(95)91688-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7475546">Abrahamov et al., 1995</a>) and British/German (<a href="#7" class="mim-tip-reference" title="Beutler, E., Gelbart, T., Demina, A., Zimran, A., LeCoutre, P. <strong>Five new Gaucher disease mutations.</strong> Blood Cells Molec. Dis. 21: 20-24, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7655857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7655857</a>] [<a href="https://doi.org/10.1006/bcmd.1995.0004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7655857">Beutler et al., 1995</a>) patients with Gaucher disease and cardiovascular calcifications. These reports demonstrate a particularly tight pan-ethnic association between phenotype and genotype in this variant form of Gaucher syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7655857+7475546" 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="#15" class="mim-tip-reference" title="Bohlega, S., Kambouris, M., Shahid, M., Al Homsi, M., Al Sous, W. <strong>Gaucher disease with oculomotor apraxia and cardiovascular calcification (Gaucher type IIIC).</strong> Neurology 54: 261-263, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10636167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10636167</a>] [<a href="https://doi.org/10.1212/wnl.54.1.261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10636167">Bohlega et al. (2000)</a> described 4 Saudi Arabian sibs with the D409H mutation who had impaired horizontal saccades and aortic and mitral valve calcification without other systemic disease. <a href="#15" class="mim-tip-reference" title="Bohlega, S., Kambouris, M., Shahid, M., Al Homsi, M., Al Sous, W. <strong>Gaucher disease with oculomotor apraxia and cardiovascular calcification (Gaucher type IIIC).</strong> Neurology 54: 261-263, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10636167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10636167</a>] [<a href="https://doi.org/10.1212/wnl.54.1.261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10636167">Bohlega et al. (2000)</a> suggested the designation 'Gaucher disease type IIIC.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10636167" 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="#54" class="mim-tip-reference" title="Inui, K., Yanagihara, K., Otani, K., Suzuki, Y., Akagi, M., Nakayama, M., Ida, H., Okada, S. <strong>A new variant neuropathic type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, and fibrous thickening of spleen and liver capsules.</strong> J. Pediat. 138: 137-139, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11148530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11148530</a>] [<a href="https://doi.org/10.1067/mpd.2001.109789" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11148530">Inui et al. (2001)</a> reported a patient who was compound heterozygous for the D409H allele and another unidentified mutation. He had hydrocephalus, corneal opacities, deformed toes, and cardiac features typical of patients who are homozygous for this allele. However, he also had fibrous thickening of the splenic and hepatic capsules and massive hepatosplenomegaly, features which differed from patients homozygous for the D409H allele. Enzyme replacement therapy was given for 4 years, resulting in an improvement of visceral and hematologic abnormalities but no neurologic improvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11148530" 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="#70" class="mim-tip-reference" title="Mignot, C., Gelot, A., Bessieres, B., Daffos, F., Voyer, M., Menez, F., Fallet Bianco, C., Odent, S., Le Duff, D., Loget, P., Fargier, P., Costil, J., Josset, P., Roume, J., Vanier, M. T., Maire, I., de Villemeur, T. B. <strong>Perinatal-lethal Gaucher disease.</strong> Am. J. Med. Genet. 120A: 338-344, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12838552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12838552</a>] [<a href="https://doi.org/10.1002/ajmg.a.20117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12838552">Mignot et al. (2003)</a> identified the D409H mutation in compound heterozygosity with another mutation in a fetus with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12838552" 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="#26" class="mim-tip-reference" title="Emre, S., Gurakan, F., Yuce, A., Rolf, A., Scott, R., Ozen, H. <strong>Molecular analysis of Turkish Gaucher disease patients: identification of novel mutations in glucocerebrosidase (GBA) gene.</strong> Europ. J. Med. Genet. 51: 315-321, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18586596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18586596</a>] [<a href="https://doi.org/10.1016/j.ejmg.2008.02.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18586596">Emre et al. (2008)</a> identified homozygosity for the D409H mutation in 2 unrelated Turkish patients with Gaucher disease, who had cardiac valvular involvement and severe cardiac disease associated with hepatosplenomegaly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18586596" 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">rs77369218 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs77369218;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=rs77369218" 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=rs77369218" 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 Caucasian patient with type III Gaucher disease (<a href="/entry/231000">231000</a>), <a href="#107" class="mim-tip-reference" title="Theophilus, B. D. M., Latham, T., Grabowski, G. A., Smith, F. I. <strong>Comparison of RNase A, a chemical cleavage and GC-clamped denaturing gradient gel electrophoresis for the detection of mutations in exon 9 of the human acid beta-glucosidase gene.</strong> Nucleic Acids Res. 17: 7707-7722, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2508065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2508065</a>] [<a href="https://doi.org/10.1093/nar/17.19.7707" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2508065">Theophilus et al. (1989)</a> identified compound heterozygosity for 2 mutations in the GBA gene: a 5958A-T transversion in exon 9, resulting in an asp409-to-val (D409V) substitution, and L444P (<a href="#0001">606463.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2508065" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The ASP409VAL variant is annotated as ASP448VAL based on sequence NM_000157.3; see <a href="#0006">606463.0006</a>. The sequence includes the 39-residue signal peptide.</p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004528 OR RCV000004529 OR RCV000004530 OR RCV000004531 OR RCV000020151 OR RCV000079343 OR RCV000762852 OR RCV001004110 OR RCV004018558 OR RCV004751200" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004528, RCV000004529, RCV000004530, RCV000004531, RCV000020151, RCV000079343, RCV000762852, RCV001004110, RCV004018558, RCV004751200" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004528...</a>
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<p><strong><em>Gaucher Disease</em></strong></p><p>
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In a non-Jewish patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#48" class="mim-tip-reference" title="Hong, C. M., Ohashi, T., Yu, X. J., Weiler, S., Barranger, J. A. <strong>Sequence of two alleles responsible for Gaucher disease.</strong> DNA Cell Biol. 9: 233-241, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1972019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1972019</a>] [<a href="https://doi.org/10.1089/dna.1990.9.233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1972019">Hong et al. (1990)</a> identified a 1504C-T transition in exon 10 of the GBA gene, resulting in an arg463-to-cys (R463C) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1972019" 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 the amplification refractory mutation system, <a href="#72" class="mim-tip-reference" title="Mistry, P. K., Smith, S. J., Ali, M., Hatton, C. S. R., McIntyre, N., Cox, T. M. <strong>Genetic diagnosis of Gaucher's disease.</strong> Lancet 339: 889-892, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1348297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1348297</a>] [<a href="https://doi.org/10.1016/0140-6736(92)90928-v" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1348297">Mistry et al. (1992)</a> identified the R463C mutation and the L444P mutation (<a href="#0001">606463.0001</a>) in association with rapidly progressive disease and neurologic involvement in non-Jewish patients (see <a href="/entry/230900">230900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1348297" 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="#79" class="mim-tip-reference" title="Park, J. K., Orvisky, E., Tayebi, N., Kaneski, C., Lamarca, M. E., Stubblefield, B. K., Martin, B. M., Schiffmann, R., Sidransky, E. <strong>Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup.</strong> Pediat. Res. 53: 387-395, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12595585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12595585</a>] [<a href="https://doi.org/10.1203/01.PDR.0000049515.79882.94" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12595585">Park et al. (2003)</a> identified the R463C mutation in patients with type III Gaucher disease (<a href="/entry/231000">231000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12595585" 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</em></strong></p><p>
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<a href="#74" class="mim-tip-reference" title="Neumann, J., Bras, J., Deas, E., O'Sullivan, S. S., Parkkinen, L., Lachmann, R. H., Li, A., Holton, J., Guerreiro, R., Paudel, R., Segarane, B., Singleton, A., Lees, A., Hardy, J., Houlden, H., Revesz, T., Wood, N. W. <strong>Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.</strong> Brain 132: 1783-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286695</a>] [<a href="https://doi.org/10.1093/brain/awp044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19286695">Neumann et al. (2009)</a> identified a heterozygous R463C mutation in 3 (0.38%) of 790 British patients with Parkinson disease (PD; <a href="/entry/168600">168600</a>) that was not found in 257 controls, suggesting that heterozygosity for the mutation increases susceptibility for development of PD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19286695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 GAUCHER DISEASE, TYPE I</strong>
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GBA, LEU444PRO, ALA456PRO, AND VAL460VAL
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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> rs1135675 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1135675;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/rs1135675?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=rs1135675" 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=rs1135675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <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> rs368060 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs368060;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/rs368060?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=rs368060" 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=rs368060" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <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> rs421016 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs421016;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/rs421016?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=rs421016" 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=rs421016" 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=RCV000004509 OR RCV000004510 OR RCV000004511 OR RCV000004512 OR RCV000004513 OR RCV000004533 OR RCV000004534 OR RCV000004535 OR RCV000004536 OR RCV000020150 OR RCV000079341 OR RCV000079342 OR RCV000225393 OR RCV000225500 OR RCV000413257 OR RCV000626625 OR RCV001004112 OR RCV001197164 OR RCV001781179 OR RCV001836696 OR RCV002476924 OR RCV003129772 OR RCV003221801 OR RCV003398445 OR RCV003987311 OR RCV004018555" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004509, RCV000004510, RCV000004511, RCV000004512, RCV000004513, RCV000004533, RCV000004534, RCV000004535, RCV000004536, RCV000020150, RCV000079341, RCV000079342, RCV000225393, RCV000225500, RCV000413257, RCV000626625, RCV001004112, RCV001197164, RCV001781179, RCV001836696, RCV002476924, RCV003129772, RCV003221801, RCV003398445, RCV003987311, RCV004018555" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004509...</a>
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<p>In 3 non-Jewish patients with Gaucher disease type I (<a href="/entry/230800">230800</a>) and 1 non-Jewish patient with type II disease (<a href="/entry/230900">230900</a>), <a href="#48" class="mim-tip-reference" title="Hong, C. M., Ohashi, T., Yu, X. J., Weiler, S., Barranger, J. A. <strong>Sequence of two alleles responsible for Gaucher disease.</strong> DNA Cell Biol. 9: 233-241, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1972019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1972019</a>] [<a href="https://doi.org/10.1089/dna.1990.9.233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1972019">Hong et al. (1990)</a> found a mutant allele containing 3 single-base substitutions in exon 10 of the GBA gene, resulting in L444P (<a href="#0001">606463.0001</a>), ala456-to-pro (A456P), and val460-to-val (V460V) substitutions. This mutant allele was referred to as 'pseudopattern' because it has sequence identical to a small region of exon 10 in the pseudogene (<a href="#49" class="mim-tip-reference" title="Horowitz, M., Wilder, S., Horowitz, Z., Reiner, O., Gelbart, T., Beutler, E. <strong>The human glucocerebrosidase gene and pseudogene: structure and evolution.</strong> Genomics 4: 87-96, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2914709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2914709</a>] [<a href="https://doi.org/10.1016/0888-7543(89)90319-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2914709">Horowitz et al., 1989</a>). At least one of the patients was a compound heterozygote; the other allele was N370S (<a href="#0003">606463.0003</a>). The authors suggested either gene conversion or recombination as a possible mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2914709+1972019" 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="#65" class="mim-tip-reference" title="Latham, T., Grabowski, G. A., Theophilus, B. D. M., Smith, F. I. <strong>Complex alleles of the acid beta-glucosidase gene in Gaucher disease.</strong> Am. J. Hum. Genet. 47: 79-86, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349952</a>]" pmid="2349952">Latham et al. (1990)</a> independently found these 3 mutations on 1 allele in patients with types I, II, and III (<a href="/entry/231000">231000</a>) Gaucher disease. None was homozygous for the complex allele: all patients had it in compound heterozygosity with another pathogenic GBA mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2349952" 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="#95" class="mim-tip-reference" title="Sidransky, E., Tayebi, N., Stubblefield, B. K., Eliason, W., Klineburgess, A., Pizzolato, G.-P., Cox, J. N., Porta, J., Bottani, A., DeLozier-Blanchet, C. D. <strong>The clinical, molecular, and pathological characterisation of a family with two cases of lethal perinatal type 2 Gaucher disease.</strong> J. Med. Genet. 33: 132-136, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8929950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8929950</a>] [<a href="https://doi.org/10.1136/jmg.33.2.132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8929950">Sidransky et al. (1996)</a> described homozygosity for this complex triply mutant allele in 2 conceptuses from an Afghan family with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>). The first infant had severe hydrops fetalis with bilateral hydrothorax and fetal hypokinesia with multiple joint contractures. Other features included hepatosplenomegaly, pulmonary hypoplasia, muscular atrophy, dysmorphic facies, and ichthyosis-like changes of the skin. The infant died less than an hour after delivery. In the next pregnancy a prenatal diagnosis of Gaucher disease was made by enzyme assay on cultured amniocytes obtained at week 15. Neither hydrops nor joint contractures were found in the fetus aborted at 23 weeks' gestation. The complex mutant allele is thought to have arisen by gene conversion or a recombination event with the neighboring pseudogene. The findings are comparable to those in the 'knockout' Gaucher mouse in which absence of enzyme is incompatible with long survival (<a href="#94" class="mim-tip-reference" title="Sidransky, E., Sherer, D. M., Ginns, E. I. <strong>Gaucher disease in the neonate: a distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene.</strong> Pediat. Res. 32: 494-498, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1437405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1437405</a>] [<a href="https://doi.org/10.1203/00006450-199210000-00023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1437405">Sidransky et al., 1992</a>; <a href="#113" class="mim-tip-reference" title="Tybulewicz, V. L. J., Tremblay, M. L., LaMarca, M. E., Willemsen, R., Stubblefield, B. K., Winfield, S., Zablocka, B., Sidransky, E., Martin, B. M., Huang, S. P., Mintzer, K. A., Westphal, H., Mulligan, R. C., Ginns, E. I. <strong>Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene.</strong> Nature 357: 407-410, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1594045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1594045</a>] [<a href="https://doi.org/10.1038/357407a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1594045">Tybulewicz et al., 1992</a>). A presumed homozygote for this complex allele, behaving as a perinatal lethal, was reported by <a href="#102" class="mim-tip-reference" title="Strasberg, P. M., Skomorowski, M. A., Warren, I. B., Hilson, W. L., Callahan, J. W., Clark, J. T. R. <strong>Homozygous presence of the crossover (fusion gene) mutation identified in a type II Gaucher disease fetus: is this analogous to the Gaucher knock-out mouse model?</strong> Biochem. Med. Metab. Biol. 53: 16-21, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7857677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7857677</a>] [<a href="https://doi.org/10.1006/bmmb.1994.1052" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7857677">Strasberg et al. (1994)</a> in a fetus of Macedonian/Ashkenazi Jewish parentage. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7857677+8929950+1594045+1437405" 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="#99" class="mim-tip-reference" title="Stone, D. L., Carey, W. F., Christodoulou, J., Sillence, D., Nelson, P., Callahan, M., Tayebi, N., Sidransky, E. <strong>Type 2 Gaucher disease: the collodion baby phenotype revisited.</strong> Arch. Dis. Child. Fetal Neonatal Ed. 82: F163-F166, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10685993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10685993</a>] [<a href="https://doi.org/10.1136/fn.82.2.f163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10685993">Stone et al. (2000)</a> reported a male infant born to consanguineous Lebanese parents who was homozygous for this recombinant allele. Ultrasound scanning demonstrated reduced fetal movement, neck hyperextension, and hepatomegaly. He was born at 34 weeks' gestation and died shortly thereafter. Autopsy findings included thick collodion-like skin, ectropia, joint contractures, hepatosplenomegaly, and facial dysmorphism. Gaucher cells were seen in many tissues. The diagnosis of Gaucher disease was confirmed enzymatically. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10685993" 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> rs74500255 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74500255;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/rs74500255?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=rs74500255" 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=rs74500255" 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=RCV000004537 OR RCV000498055 OR RCV001004127 OR RCV001248860 OR RCV001705580 OR RCV002476925" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004537, RCV000498055, RCV001004127, RCV001248860, RCV001705580, RCV002476925" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004537...</a>
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<p>In an 11-year-old, non-Jewish Caucasian girl with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#11" class="mim-tip-reference" title="Beutler, E., Gelbart, T. <strong>Gaucher disease associated with a unique KpnI restriction site: identification of the amino-acid substitution.</strong> Ann. Hum. Genet. 54: 149-153, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1974409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1974409</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1990.tb00371.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1974409">Beutler and Gelbart (1990)</a> identified a 764T-A transversion in the GBA gene, resulting in a phe216-to-tyr (F216Y) substitution. The patient was heterozygous for this mutation, which came from the father; the presumed abnormality in the other allele was not identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1974409" 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> rs147138516 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs147138516;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/rs147138516?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=rs147138516" 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=rs147138516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <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> rs2230288 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2230288;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/rs2230288?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=rs2230288" 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=rs2230288" 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=RCV000004538 OR RCV000252989 OR RCV000414984 OR RCV000415149 OR RCV000415387 OR RCV000487503 OR RCV000487788 OR RCV000586576 OR RCV001248923 OR RCV001509572 OR RCV001836745 OR RCV002468938 OR RCV004594032" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004538, RCV000252989, RCV000414984, RCV000415149, RCV000415387, RCV000487503, RCV000487788, RCV000586576, RCV001248923, RCV001509572, RCV001836745, RCV002468938, RCV004594032" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004538...</a>
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<p>In 2 brothers with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#28" class="mim-tip-reference" title="Eyal, N., Firon, N., Wilder, S., Kolodny, E. H., Horowitz, M. <strong>Three unique base pair changes in a family with Gaucher disease.</strong> Hum. Genet. 87: 328-332, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1864608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1864608</a>] [<a href="https://doi.org/10.1007/BF00200914" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1864608">Eyal et al. (1991)</a> identified 3 point mutations in the GBA gene. One chromosome, inherited from the mother, had a 3119G-A transition resulting in an asp140-to-his (D140H) substitution, and a 5309G-A transition resulting in a glu326-to-lys (E326K) substitution. The other chromosome, inherited from the father, had a 3170A-C transversion resulting in a lys157-to-gln (K157Q; <a href="#0012">606463.0012</a>) substitution. All 3 mutations were inherited through 3 generations; the his140 and lys326 mutations were transmitted together. Although 1 brother had neurologic features, postmortem analysis did not detect Gaucher cells in the central nervous system, and <a href="#28" class="mim-tip-reference" title="Eyal, N., Firon, N., Wilder, S., Kolodny, E. H., Horowitz, M. <strong>Three unique base pair changes in a family with Gaucher disease.</strong> Hum. Genet. 87: 328-332, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1864608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1864608</a>] [<a href="https://doi.org/10.1007/BF00200914" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1864608">Eyal et al. (1991)</a> concluded that he had an additional separate neurologic disorder. The other brother had clinical features consistent with type I Gaucher disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1864608" 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 functional analysis studies of mutant GBA proteins, <a href="#73" class="mim-tip-reference" title="Montfort, M., Chabas, A., Vilageliu, L., Grinberg, D. <strong>Functional analysis of 13 GBA mutant alleles identified in Gaucher disease patients: pathogenic changes and 'modifier' polymorphisms.</strong> Hum. Mutat. 23: 567-575, 2004. Note: Erratum: Hum. Mutat. 26: 276 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146461</a>] [<a href="https://doi.org/10.1002/humu.20043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146461">Montfort et al. (2004)</a> obtained results suggesting that the E326K substitution alone could be considered a 'modifier variant' rather than a neutral polymorphism, as previously suggested (<a href="#41" class="mim-tip-reference" title="Grace, M. E., Ashton-Prolla, P., Pastores, G. M., Soni, A., Desnick, R. J. <strong>Non-pseudogene-derived complex acid beta-glucosidase mutations causing mild type 1 and severe type 2 Gaucher disease.</strong> J. Clin. Invest. 103: 817-823, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10079102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10079102</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10079102[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI5168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10079102">Grace et al., 1999</a>; <a href="#80" class="mim-tip-reference" title="Park, J. K., Tayebi, N., Stubblefield, B. K., LaMarca, M. E., MacKenzie, J. J., Stone, D. L., Sidransky, E. <strong>The E326K mutation and Gaucher disease: mutation or polymorphism?</strong> Clin. Genet. 61: 32-34, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11903352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11903352</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.610106.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11903352">Park et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10079102+15146461+11903352" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 GAUCHER DISEASE, TYPE I</strong>
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GBA, LYS157GLN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908297 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908297;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=rs121908297" 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=rs121908297" 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=RCV000004539 OR RCV001572837" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004539, RCV001572837" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004539...</a>
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<p>For discussion of the 3170A-C transversion in the GBA gene, resulting in a lys157-to-gln (K157Q) substitution, that was found in compound heterozygous state in 2 brothers with type I Gaucher disease (<a href="/entry/230800">230800</a>) by <a href="#28" class="mim-tip-reference" title="Eyal, N., Firon, N., Wilder, S., Kolodny, E. H., Horowitz, M. <strong>Three unique base pair changes in a family with Gaucher disease.</strong> Hum. Genet. 87: 328-332, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1864608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1864608</a>] [<a href="https://doi.org/10.1007/BF00200914" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1864608">Eyal et al. (1991)</a>, see <a href="#0011">606463.0011</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1864608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 GAUCHER DISEASE, TYPE III</strong>
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GAUCHER DISEASE, TYPE II, INCLUDED<br />
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GAUCHER DISEASE, TYPE I, 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> rs381737 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs381737;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/rs381737?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=rs381737" 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=rs381737" 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=RCV000004540 OR RCV000004541 OR RCV000004542 OR RCV000020158 OR RCV000790654 OR RCV002482827 OR RCV004018559 OR RCV004820816" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004540, RCV000004541, RCV000004542, RCV000020158, RCV000790654, RCV002482827, RCV004018559, RCV004820816" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004540...</a>
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<p>In a Japanese patient with type III Gaucher disease (<a href="/entry/231000">231000</a>), <a href="#57" class="mim-tip-reference" title="Kawame, H., Eto, Y. <strong>A new glucocerebrosidase-gene missense mutation responsible for neuronopathic Gaucher disease in Japanese patients.</strong> Am. J. Hum. Genet. 49: 1378-1380, 1991. Note: Erratum: Am. J. Hum. Genet. 50: 885 only, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1840477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1840477</a>]" pmid="1840477">Kawame and Eto (1991)</a> identified a heterozygous 3548T-A transition in exon 6 of the GBA gene, resulting in a phe213-to-ile (F213I) substitution. Two additional unrelated Japanese patients with type II Gaucher disease (<a href="/entry/230900">230900</a>) were also found to carry this mutation. F231I is normally found in the GBA pseudogene. The patients were compound heterozygous for F213I and L444P (<a href="#0001">606463.0001</a>). In a patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#47" class="mim-tip-reference" title="He, G.-S., Grace, M. E., Grabowski, G. A. <strong>Gaucher disease: four rare alleles encoding F213I, P289L, T323I, and R463C in type 1 variants.</strong> Hum. Mutat. 1: 423-427, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301953</a>] [<a href="https://doi.org/10.1002/humu.1380010513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301953">He et al. (1992)</a> found compound heterozygosity for 2 mutations in the GBA gene: P213I and P289L (<a href="#0016">606463.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1301953+1840477" 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 GAUCHER DISEASE, TYPE I</strong>
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GBA, 1-BP INS, 84G
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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> rs387906315 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906315;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/rs387906315?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=rs387906315" 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=rs387906315" 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=RCV000004543 OR RCV000587723 OR RCV000790704 OR RCV001004138 OR RCV002476926 OR RCV004751201" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004543, RCV000587723, RCV000790704, RCV001004138, RCV002476926, RCV004751201" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004543...</a>
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<p>In Ashkenazi Jewish patients with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#8" class="mim-tip-reference" title="Beutler, E., Gelbart, T., Kuhl, W., Sorge, J., West, C. <strong>Identification of the second common Jewish Gaucher disease mutation makes possible population-based screening for the heterozygous state.</strong> Proc. Nat. Acad. Sci. 88: 10544-10547, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1961718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1961718</a>] [<a href="https://doi.org/10.1073/pnas.88.23.10544" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1961718">Beutler et al. (1991)</a> identified a 1-bp insertion (84insG) of a second guanine at cDNA nucleotide 84; the mutation was referred to as the '84GG' mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1961718" 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="Beutler, E., Gelbart, T., West, C. <strong>Identification of six new Gaucher disease mutations.</strong> Genomics 15: 203-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432537</a>] [<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432537">Beutler et al. (1993)</a> found that 10 of 2,305 normal Ashkenazi Jewish individuals were heterozygous for the 84GG insertion mutation, yielding an allele frequency of 0.00217. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432537" 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="#53" class="mim-tip-reference" title="Ida, H., Iwasawa, K., Kawame, H., Rennert, O. M., Maekawa, K., Eto, Y. <strong>Characteristics of gene mutations among 32 unrelated Japanese Gaucher disease patients: absence of the common Jewish 84GG and 1226G mutations.</strong> Hum. Genet. 95: 717-720, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789963</a>] [<a href="https://doi.org/10.1007/BF00209497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789963">Ida et al. (1995)</a> did not identify the 84GG mutation in 32 unrelated Japanese Gaucher patients, of whom 20 were type I, 6 were type II (<a href="/entry/230900">230900</a>), and 6 were type III (<a href="/entry/231000">231000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789963" 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 GAUCHER DISEASE, TYPE I</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> rs104886460 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104886460;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/rs104886460?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=rs104886460" 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=rs104886460" 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=RCV000004546 OR RCV000032094 OR RCV000177098 OR RCV000762856 OR RCV000790724 OR RCV001004137 OR RCV001253701 OR RCV004019534" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004546, RCV000032094, RCV000177098, RCV000762856, RCV000790724, RCV001004137, RCV001253701, RCV004019534" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004546...</a>
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<p>In a survey of 100 unrelated Jewish patients with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#9" class="mim-tip-reference" title="Beutler, E., Gelbart, T., Kuhl, W., Zimran, A., West, C. <strong>Mutations in Jewish patients with Gaucher disease.</strong> Blood 79: 1662-1666, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1558964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1558964</a>]" pmid="1558964">Beutler et al. (1992)</a> found that 5 of the mutant GBA alleles resulted from a splice site mutation in intron 2 (IVS2DS+1G-A), resulting in skipping of exon 2. The phenotype was associated with earlier onset and more severe disease compared to the common N370S mutation (<a href="#0003">606463.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1558964" 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="#46" class="mim-tip-reference" title="He, G.-S., Grabowski, G. A. <strong>Gaucher disease: a G(+1)-to-A(+1) IVS2 splice donor site mutation causing exon 2 skipping in the acid beta-glucosidase mRNA.</strong> Am. J. Hum. Genet. 51: 810-820, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1415223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1415223</a>]" pmid="1415223">He and Grabowski (1992)</a> identified the IVS2DS+1G-A transition in a moderately affected 9-year-old Ashkenazi Jewish patient with type I Gaucher disease. The transition was found also at the corresponding exon/intron boundary of the highly homologous pseudogene. This splicing mutation accounted for about 3.4% of the Gaucher disease alleles in the Ashkenazi Jewish population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1415223" 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="#100" class="mim-tip-reference" title="Stone, D. L., Tayebi, N., Orvisky, E., Stubblefield, B., Madike, V., Sidransky, E. <strong>Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease.</strong> Hum. Mutat. 15: 181-188, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10649495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10649495</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200002)15:2<181::AID-HUMU7>3.0.CO;2-S" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10649495">Stone et al. (2000)</a> identified compound heterozygosity for the IVS2DS+1G-A mutation and L444P (<a href="#0001">606463.0001</a>) in 2 unrelated patients with type II Gaucher disease (<a href="/entry/230900">230900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10649495" 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">rs121908298 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908298;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=rs121908298" 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=rs121908298" 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=RCV000004547" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004547" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004547</a>
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<p>In a patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#47" class="mim-tip-reference" title="He, G.-S., Grace, M. E., Grabowski, G. A. <strong>Gaucher disease: four rare alleles encoding F213I, P289L, T323I, and R463C in type 1 variants.</strong> Hum. Mutat. 1: 423-427, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301953</a>] [<a href="https://doi.org/10.1002/humu.1380010513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301953">He et al. (1992)</a> found compound heterozygosity for 2 mutations in the GBA gene: a pro289-to-leu (P289L) and P213I (<a href="#0013">606463.0013</a>) substitution. The latter mutation had previously been found in type III patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0017 GAUCHER DISEASE, TYPE I</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> rs76539814 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs76539814;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/rs76539814?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=rs76539814" 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=rs76539814" 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=RCV000004548 OR RCV000041967 OR RCV001193934 OR RCV002496255 OR RCV003137492" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004548, RCV000041967, RCV001193934, RCV002496255, RCV003137492" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004548...</a>
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<p>In a patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#47" class="mim-tip-reference" title="He, G.-S., Grace, M. E., Grabowski, G. A. <strong>Gaucher disease: four rare alleles encoding F213I, P289L, T323I, and R463C in type 1 variants.</strong> Hum. Mutat. 1: 423-427, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301953</a>] [<a href="https://doi.org/10.1002/humu.1380010513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301953">He et al. (1992)</a> found compound heterozygosity for a thr323-to-ile (T323I) substitution and the R463C (<a href="#0008">606463.0008</a>) mutation in the GBA gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301953" 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 infant with severe, lethal type II Gaucher disease (<a href="/entry/230900">230900</a>) and severely decreased glucocerebrosidase activity, <a href="#88" class="mim-tip-reference" title="Saranjam, H., Chopra, S. S., Levy, H., Stubblefield, B. K., Maniwang, E., Cohen, I. J., Baris, H., Sidransky, E., Tayebi, N. <strong>A germline or de novo mutation in two families with Gaucher disease: implications for recessive disorders.</strong> Europ. J. Hum. Genet. 21: 115-117, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22713811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22713811</a>] [<a href="https://doi.org/10.1038/ejhg.2012.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22713811">Saranjam et al. (2013)</a> identified compound heterozygosity for 2 mutations in the GBA gene: a c.1085C-T transition, resulting in a thr323-to-ile (T323I) substitution inherited from the unaffected father, and the common L444P mutation (<a href="#0001">606463.0001</a>). However, the L444P mutation was not identified in several tissues from the mother, and her glucocerebrosidase activity was normal. The findings suggested that the L444P mutation occurred either as a result of germline mosaicism or as a de novo mutation in 1 ovum that took place during cell division. The findings had implications for genetic counseling, in that even if only 1 parent is found to be a carrier for a recessive disorder, the chance of having an affected child may not be zero. <a href="#88" class="mim-tip-reference" title="Saranjam, H., Chopra, S. S., Levy, H., Stubblefield, B. K., Maniwang, E., Cohen, I. J., Baris, H., Sidransky, E., Tayebi, N. <strong>A germline or de novo mutation in two families with Gaucher disease: implications for recessive disorders.</strong> Europ. J. Hum. Genet. 21: 115-117, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22713811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22713811</a>] [<a href="https://doi.org/10.1038/ejhg.2012.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22713811">Saranjam et al. (2013)</a> noted that the L444P change occurs at a known mutational hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22713811" 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="#88" class="mim-tip-reference" title="Saranjam, H., Chopra, S. S., Levy, H., Stubblefield, B. K., Maniwang, E., Cohen, I. J., Baris, H., Sidransky, E., Tayebi, N. <strong>A germline or de novo mutation in two families with Gaucher disease: implications for recessive disorders.</strong> Europ. J. Hum. Genet. 21: 115-117, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22713811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22713811</a>] [<a href="https://doi.org/10.1038/ejhg.2012.105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22713811">Saranjam et al. (2013)</a> alternatively referred to this mutation as THR362ILE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22713811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0018 GAUCHER DISEASE, TYPE I</strong>
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GBA, 1-BP DEL, 72C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397518433 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397518433;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=rs397518433" 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=rs397518433" 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=RCV000004549" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004549" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004549</a>
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<p>In a 6-year-old non-Jewish European patient with Gaucher disease type I (<a href="/entry/230800">230800</a>), <a href="#10" class="mim-tip-reference" title="Beutler, E., Gelbart, T., West, C. <strong>Identification of six new Gaucher disease mutations.</strong> Genomics 15: 203-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432537</a>] [<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432537">Beutler et al. (1993)</a> identified a 1-bp deletion (72delC; 1023delC in the genomic sequence) in the GBA gene. The nature of the other mutation was not determined. There were no neurologic findings. The mutation was suspected on the basis of SSCP analysis and confirmed by sequencing and by restriction endonuclease analysis. In this and the other 5 patients with 'new' mutations whom they described, <a href="#10" class="mim-tip-reference" title="Beutler, E., Gelbart, T., West, C. <strong>Identification of six new Gaucher disease mutations.</strong> Genomics 15: 203-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432537</a>] [<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432537">Beutler et al. (1993)</a> cited a severity score which varied in the group of patients from 2 to 15; the patient with the 1023delC mutation had a severity score of 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0019" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0019 GAUCHER DISEASE, TYPE I</strong>
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</h4>
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GBA, PRO122SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908299 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908299;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=rs121908299" 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=rs121908299" 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=RCV000004550" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004550" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004550</a>
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</span>
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<span class="mim-text-font">
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<p><a href="#10" class="mim-tip-reference" title="Beutler, E., Gelbart, T., West, C. <strong>Identification of six new Gaucher disease mutations.</strong> Genomics 15: 203-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432537</a>] [<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432537">Beutler et al. (1993)</a> identified homozygosity for a pro122-to-ser (P122S) mutation in a 3-year-old Native American patient with Gaucher disease type I (<a href="/entry/230800">230800</a>) of severity score 12 and no neurologic findings. The amino acid substitution was due to a 3065C-T transition (genomic DNA sequence) and abolished a KpnI restriction site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0020" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0020 GAUCHER DISEASE, TYPE I</strong>
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</span>
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</h4>
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GBA, TYR212HIS
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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> rs121908300 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908300;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/rs121908300?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=rs121908300" 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=rs121908300" 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=RCV000004551 OR RCV001248859 OR RCV003133115" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004551, RCV001248859, RCV003133115" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004551...</a>
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</span>
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<div>
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<span class="mim-text-font">
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<p>In a Jewish patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#10" class="mim-tip-reference" title="Beutler, E., Gelbart, T., West, C. <strong>Identification of six new Gaucher disease mutations.</strong> Genomics 15: 203-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432537</a>] [<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432537">Beutler et al. (1993)</a> identified compound heterozygosity for 2 mutations in the GBA gene: a 751T-C transition (3545T-C in the genomic DNA), resulting in a tyr212-to-his (Y212H) substitution, and N370S (<a href="#0003">606463.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432537" 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>
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<a id="0021" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0021 GAUCHER DISEASE, TYPE I</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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GBA, GLY478SER
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</div>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908301 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908301;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=rs121908301" 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=rs121908301" 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=RCV000004552 OR RCV001171764 OR RCV004689409" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004552, RCV001171764, RCV004689409" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004552...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a non-Jewish European patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#10" class="mim-tip-reference" title="Beutler, E., Gelbart, T., West, C. <strong>Identification of six new Gaucher disease mutations.</strong> Genomics 15: 203-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432537</a>] [<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432537">Beutler et al. (1993)</a> identified compound heterozygosity for 2 mutations in the GBA gene: a 1549G-A transition (6628G-A in the genomic DNA) resulting in a gly478-to-ser (G478S) substitution, and N370S (<a href="#0003">606463.0003</a>). The severity score was given as 15, the highest value in this particular series of reported cases. There were no neurologic symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432537" 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>
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</div>
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<div>
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<a id="0022" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0022 GAUCHER DISEASE, TYPE I</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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GBA, ARG496HIS
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</div>
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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> rs75822236 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75822236;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/rs75822236?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=rs75822236" 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=rs75822236" 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=RCV000004553 OR RCV000020153 OR RCV000762851 OR RCV000790684 OR RCV001004108 OR RCV001836698 OR RCV004018560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004553, RCV000020153, RCV000762851, RCV000790684, RCV001004108, RCV001836698, RCV004018560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004553...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 unrelated patients, 3 Jewish and 1 non-Jewish European, with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#10" class="mim-tip-reference" title="Beutler, E., Gelbart, T., West, C. <strong>Identification of six new Gaucher disease mutations.</strong> Genomics 15: 203-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432537</a>] [<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432537">Beutler et al. (1993)</a> identified a heterozygous 1604G-A transition (6683 in the genomic DNA sequence) in the GBA gene, resulting in an arg496-to-his (R496H) substitution. Age at diagnosis varied from 16 to 27 years. None had neurologic findings. Severity score varied from 2 to 9. The other mutation in 3 of the patients was that referred to as 84GG (<a href="#0014">606463.0014</a>); the fourth patient, Jewish, had the common N370S mutation (<a href="#0003">606463.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432537" 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>
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<div>
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<a id="0023" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0023 GAUCHER DISEASE, TYPE I</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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GAUCHER DISEASE, PERINATAL LETHAL, INCLUDED
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</span>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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GBA, 55-BP DEL
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356768 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356768;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=rs80356768" 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=rs80356768" 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=RCV000004555 OR RCV000020147 OR RCV000173718 OR RCV000723462 OR RCV002500459" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004555, RCV000020147, RCV000173718, RCV000723462, RCV002500459" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004555...</a>
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<p>In a non-Jewish European patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#10" class="mim-tip-reference" title="Beutler, E., Gelbart, T., West, C. <strong>Identification of six new Gaucher disease mutations.</strong> Genomics 15: 203-205, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432537</a>] [<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432537">Beutler et al. (1993)</a> identified a 55-bp deletion (nucleotides 1263-1317 in the cDNA; nucleotides 5879-5933 in genomic DNA) in the GBA gene. The mutation was in compound heterozygous combination with the N370S mutation (<a href="#0003">606463.0003</a>). The severity score was given as 12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432537" 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="#99" class="mim-tip-reference" title="Stone, D. L., Carey, W. F., Christodoulou, J., Sillence, D., Nelson, P., Callahan, M., Tayebi, N., Sidransky, E. <strong>Type 2 Gaucher disease: the collodion baby phenotype revisited.</strong> Arch. Dis. Child. Fetal Neonatal Ed. 82: F163-F166, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10685993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10685993</a>] [<a href="https://doi.org/10.1136/fn.82.2.f163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10685993">Stone et al. (2000)</a> reported a preterm female infant, born to nonconsanguineous Australian parents, with collodion skin, ectropia, hepatosplenomegaly, and thrombocytopenia (<a href="/entry/608013">608013</a>). She had a leucocyte glucocerebrosidase activity of 53 pmol/min/mg (normal, 600-3200). She was compound heterozygous for the 55-bp deletion and an R257E substitution (<a href="#0041">606463.0041</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10685993" 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>.0024 GAUCHER DISEASE, TYPE I</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">rs121908302 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908302;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=rs121908302" 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=rs121908302" 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=RCV000004556" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004556" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004556</a>
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<p>By sequencing RT-PCR cDNAs from 5 unrelated Korean and 2 Taiwanese sibs with Gaucher disease type I (<a href="/entry/230800">230800</a>), <a href="#58" class="mim-tip-reference" title="Kim, J.-W., Liou, B. B., Lai, M.-Y., Ponce, E., Grabowski, G. A. <strong>Gaucher disease: identification of three new mutations in the Korean and Chinese (Taiwanese) populations.</strong> Hum. Mutat. 7: 214-218, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8829654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8829654</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:3<214::AID-HUMU5>3.0.CO;2-A" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8829654">Kim et al. (1996)</a> identified 3 mutations in the GBA gene: V15L, G46E (<a href="#0025">606463.0025</a>), and N188S (<a href="#0026">606463.0026</a>). Each mutation resulted in a dysfunctional acid beta-glucosidase. The N188S allele was present in both the Korean and the Chinese populations, suggesting an ancient mutation. The G46E mutation was present in 2 unrelated Korean patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8829654" 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>.0025 GAUCHER DISEASE, TYPE I</strong>
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GBA, GLY46GLU
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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> rs77829017 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs77829017;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/rs77829017?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=rs77829017" 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=rs77829017" 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=RCV000004532 OR RCV000781409 OR RCV004589496" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004532, RCV000781409, RCV004589496" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004532...</a>
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<p><a href="#58" class="mim-tip-reference" title="Kim, J.-W., Liou, B. B., Lai, M.-Y., Ponce, E., Grabowski, G. A. <strong>Gaucher disease: identification of three new mutations in the Korean and Chinese (Taiwanese) populations.</strong> Hum. Mutat. 7: 214-218, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8829654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8829654</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:3<214::AID-HUMU5>3.0.CO;2-A" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8829654">Kim et al. (1996)</a> identified a gly46-to-glu (G46E) substitution in the GBA gene in 2 unrelated Korean patients with type I Gaucher disease (<a href="/entry/230800">230800</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8829654" 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>.0026 GAUCHER DISEASE, TYPE I</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> rs364897 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs364897;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/rs364897?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=rs364897" 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=rs364897" 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=RCV000004557 OR RCV000004558 OR RCV000020156 OR RCV000723402 OR RCV001004131 OR RCV002504742 OR RCV005089160" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004557, RCV000004558, RCV000020156, RCV000723402, RCV001004131, RCV002504742, RCV005089160" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004557...</a>
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<p><a href="#58" class="mim-tip-reference" title="Kim, J.-W., Liou, B. B., Lai, M.-Y., Ponce, E., Grabowski, G. A. <strong>Gaucher disease: identification of three new mutations in the Korean and Chinese (Taiwanese) populations.</strong> Hum. Mutat. 7: 214-218, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8829654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8829654</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:3<214::AID-HUMU5>3.0.CO;2-A" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8829654">Kim et al. (1996)</a> identified an asn188-to-ser (N188S) substitution in the GBA gene in both Korean and Chinese (Taiwanese) patients with type I Gaucher disease (<a href="/entry/230800">230800</a>), suggesting that this is an ancient mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8829654" 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="#79" class="mim-tip-reference" title="Park, J. K., Orvisky, E., Tayebi, N., Kaneski, C., Lamarca, M. E., Stubblefield, B. K., Martin, B. M., Schiffmann, R., Sidransky, E. <strong>Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup.</strong> Pediat. Res. 53: 387-395, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12595585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12595585</a>] [<a href="https://doi.org/10.1203/01.PDR.0000049515.79882.94" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12595585">Park et al. (2003)</a> identified a heterozygous N188S mutation in 4 unrelated adult patients with type III Gaucher disease and myoclonic epilepsy (<a href="/entry/231000">231000</a>). All were compound heterozygous for another pathogenic GBA mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12595585" 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="#73" class="mim-tip-reference" title="Montfort, M., Chabas, A., Vilageliu, L., Grinberg, D. <strong>Functional analysis of 13 GBA mutant alleles identified in Gaucher disease patients: pathogenic changes and 'modifier' polymorphisms.</strong> Hum. Mutat. 23: 567-575, 2004. Note: Erratum: Hum. Mutat. 26: 276 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15146461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15146461</a>] [<a href="https://doi.org/10.1002/humu.20043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15146461">Montfort et al. (2004)</a> demonstrated that the N188S mutant enzyme retains a relatively high level of activity, suggesting that it is probably a very mild mutation or a modifier variant. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15146461" 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>.0027 GAUCHER DISEASE, TYPE I</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">rs121908303 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908303;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=rs121908303" 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=rs121908303" 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=RCV000004559" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004559" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004559</a>
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<p>In a patient with Gaucher disease type I (<a href="/entry/230800">230800</a>), <a href="#50" class="mim-tip-reference" title="Horowitz, M., Zimran, A. <strong>Mutations causing Gaucher disease.</strong> Hum. Mutat. 3: 1-11, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8118460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8118460</a>] [<a href="https://doi.org/10.1002/humu.1380030102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8118460">Horowitz and Zimran (1994)</a> reported a 4113T-A transversion of the GBA gene leading to a change from phenylalanine to valine at position 216. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8118460" 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>.0028 GAUCHER DISEASE, TYPE I</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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GBA, ALA309VAL
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs78396650 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs78396650;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/rs78396650?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=rs78396650" 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=rs78396650" 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=RCV000004560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004560</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#64" class="mim-tip-reference" title="Latham, T. E., Theophilus, B. D. M., Grabowski, G. A., Smith, F. I. <strong>Heterogeneity of mutations in the acid beta-glucosidase gene of Gaucher disease patients.</strong> DNA Cell Biol. 10: 15-21, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1899336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1899336</a>] [<a href="https://doi.org/10.1089/dna.1991.10.15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1899336">Latham et al. (1991)</a> identified a 5259G-T transversion in the GBA gene, resulting in an ala309-to-val (A309V) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1899336" 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>
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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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<a id="0029" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0029 GAUCHER DISEASE, TYPE I</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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GBA, TRP312CYS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908304 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908304;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=rs121908304" 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=rs121908304" 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=RCV000004561" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004561" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004561</a>
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#64" class="mim-tip-reference" title="Latham, T. E., Theophilus, B. D. M., Grabowski, G. A., Smith, F. I. <strong>Heterogeneity of mutations in the acid beta-glucosidase gene of Gaucher disease patients.</strong> DNA Cell Biol. 10: 15-21, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1899336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1899336</a>] [<a href="https://doi.org/10.1089/dna.1991.10.15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1899336">Latham et al. (1991)</a> identified a 5269G-T transversion in the GBA gene, resulting in a trp312-to-cys (W312C) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1899336" 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>
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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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<a id="0030" class="mim-anchor"></a>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0030 GAUCHER DISEASE, TYPE II</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
|
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GBA, GLY325ARG
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908305 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908305;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/rs121908305?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=rs121908305" 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=rs121908305" 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">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004562 OR RCV000180535 OR RCV001197976 OR RCV001248922 OR RCV002504743" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004562, RCV000180535, RCV001197976, RCV001248922, RCV002504743" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004562...</a>
|
|
</span>
|
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</div>
|
|
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|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type II Gaucher disease (<a href="/entry/230900">230900</a>), <a href="#29" class="mim-tip-reference" title="Eyal, N., Wilder, S., Horowitz, M. <strong>Prevalent and rare mutations among Gaucher patients.</strong> Gene 96: 277-283, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2269438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2269438</a>] [<a href="https://doi.org/10.1016/0378-1119(90)90264-r" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2269438">Eyal et al. (1990)</a> identified compound heterozygosity for 2 mutations in the GBA gene: a 5306G-A transition, resulting in a gly325-to-arg (G325R) substitution, and C342G (<a href="#0031">606463.0031</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2269438" 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>
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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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|
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<div>
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|
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|
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<div>
|
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<a id="0031" class="mim-anchor"></a>
|
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<h4>
|
|
<span class="mim-font">
|
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<strong>.0031 GAUCHER DISEASE, TYPE II</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
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<div style="float: left;">
|
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GBA, CYS342GLY
|
|
</div>
|
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|
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</span>
|
|
|
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|
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|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908306 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908306;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=rs121908306" 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=rs121908306" 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">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004563" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004563" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004563</a>
|
|
</span>
|
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|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type II Gaucher disease (<a href="/entry/230900">230900</a>), <a href="#29" class="mim-tip-reference" title="Eyal, N., Wilder, S., Horowitz, M. <strong>Prevalent and rare mutations among Gaucher patients.</strong> Gene 96: 277-283, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2269438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2269438</a>] [<a href="https://doi.org/10.1016/0378-1119(90)90264-r" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2269438">Eyal et al. (1990)</a> identified compound heterozygosity for 2 mutations in the GBA gene: a 5357T-G transversion, resulting in a cys342-to-gly (C342G) substitution, and G325R (<a href="#0030">606463.0030</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2269438" 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>
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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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<a id="0032" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>.0032 GAUCHER DISEASE, TYPE I</strong>
|
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
|
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GBA, SER364THR
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</div>
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</span>
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|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908307 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908307;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/rs121908307?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=rs121908307" 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=rs121908307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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|
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<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004564 OR RCV002281038" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004564, RCV002281038" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004564...</a>
|
|
</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#64" class="mim-tip-reference" title="Latham, T. E., Theophilus, B. D. M., Grabowski, G. A., Smith, F. I. <strong>Heterogeneity of mutations in the acid beta-glucosidase gene of Gaucher disease patients.</strong> DNA Cell Biol. 10: 15-21, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1899336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1899336</a>] [<a href="https://doi.org/10.1089/dna.1991.10.15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1899336">Latham et al. (1991)</a> identified a 5424G-C transversion in the GBA gene, resulting in a ser364-to-thr (S364T) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1899336" 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>
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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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<a id="0033" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>.0033 GAUCHER DISEASE, TYPE I</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
|
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GBA, 259C-T
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1141814 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1141814;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/rs1141814?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=rs1141814" 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=rs1141814" 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=RCV000004565 OR RCV000589792 OR RCV001507457 OR RCV002247245 OR RCV002251874 OR RCV002476927 OR RCV004760320" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004565, RCV000589792, RCV001507457, RCV002247245, RCV002251874, RCV002476927, RCV004760320" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004565...</a>
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Bedouin patient with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#85" class="mim-tip-reference" title="Rockah, R., Narinsky, R., Hatskelzon, L., Frisch, A. <strong>Type I Gaucher disease due to homozygosity for the 259T mutation in a Bedouin patient.</strong> Am. J. Med. Genet. 72: 77-78, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9295080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9295080</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971003)72:1<77::aid-ajmg16>3.0.co;2-r" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9295080">Rockah et al. (1997)</a> identified a homozygous 259C-T transition (1763 genomic DNA) in the GBA gene. The patient was 26 years old and had moderate thrombocytopenia and an enlarged spleen and liver, as well as Gaucher cells in a bone marrow biopsy and low levels of glucocerebrosidase activity. The same mutation in compound heterozygous state had been described by <a href="#7" class="mim-tip-reference" title="Beutler, E., Gelbart, T., Demina, A., Zimran, A., LeCoutre, P. <strong>Five new Gaucher disease mutations.</strong> Blood Cells Molec. Dis. 21: 20-24, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7655857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7655857</a>] [<a href="https://doi.org/10.1006/bcmd.1995.0004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7655857">Beutler et al. (1995)</a> in a Bedouin patient with type I Gaucher disease; this patient carried a 1448G mutation in addition to the 259T mutation. His phenotype was severe but with no neurologic signs. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9295080+7655857" 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>.0034 GAUCHER DISEASE, PERINATAL LETHAL</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">rs397518434 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397518434;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=rs397518434" 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=rs397518434" 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=RCV000004566 OR RCV001580445" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004566, RCV001580445" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004566...</a>
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<p>In a fetus with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>), <a href="#104" class="mim-tip-reference" title="Tayebi, N., Cushner, S. R., Kleijer, W., Lau, E. K., Damschroder-Williams, P. J., Stubblefield, B. K., Den Hollander, J., Sidransky, E. <strong>Prenatal lethality of a homozygous null mutation in the human glucocerebrosidase gene.</strong> Am. J. Med. Genet. 73: 41-47, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9375921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9375921</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971128)73:1<41::aid-ajmg9>3.0.co;2-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9375921">Tayebi et al. (1997)</a> identified a homozygous 1-bp deletion in the GBA gene, resulting in a frameshift and premature termination of the protein in exon 6. This 22-week-old fetus, the offspring of a first-cousin marriage, had hydrops, external abnormalities, hepatosplenomegaly, and Gaucher cells in several organs. Western blot analysis confirmed absence of glucocerebrosidase protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9375921" 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>.0035 GAUCHER DISEASE, TYPE III</strong>
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GBA, ARG353GLY
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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> rs121908308 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908308;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/rs121908308?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=rs121908308" 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=rs121908308" 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=RCV000004567" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004567" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004567</a>
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<p>In 3 sibs with Gaucher disease with neurologic involvement (<a href="/entry/231000">231000</a>), born of parents related as first cousins once removed, <a href="#78" class="mim-tip-reference" title="Parenti, G., Filocamo, M., Titomanlio, L., Rizzolo, M. G., Silvestro, E., Perretti, A., Gatti, R., Andria, G. <strong>A novel mutation of the beta-glucocererebrosidase (sic) gene associated with neurologic manifestations in three sibs.</strong> Clin. Genet. 53: 281-285, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9650766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9650766</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1998.tb02697.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9650766">Parenti et al. (1998)</a> identified a 5390C-G transversion in the GBA gene, resulting in an arg353-to-gly (R353G) substitution. The 3 affected sibs were all adults, the youngest being 26 years old. Neurologic signs observed in type III Gaucher disease, such as deficits of the saccadic eye movements, cerebellar abnormalities, or myoclonus, were not present in these 3 sisters. However, the oldest sister had generalized tonic-clonic seizures beginning at the age of 23 years, requiring therapy. The next younger sister with Gaucher disease had partial seizures, and the youngest sister with Gaucher disease had EEG and other electrophysiologic abnormalities indicative of dysfunction of the motor cortex. Since none of these clinical or laboratory findings were present in the sibs without Gaucher disease, <a href="#78" class="mim-tip-reference" title="Parenti, G., Filocamo, M., Titomanlio, L., Rizzolo, M. G., Silvestro, E., Perretti, A., Gatti, R., Andria, G. <strong>A novel mutation of the beta-glucocererebrosidase (sic) gene associated with neurologic manifestations in three sibs.</strong> Clin. Genet. 53: 281-285, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9650766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9650766</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1998.tb02697.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9650766">Parenti et al. (1998)</a> concluded that the GBA mutation was responsible for the neurologic involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9650766" 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>.0036 GAUCHER DISEASE, TYPE I</strong>
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GBA, PRO401LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs74598136 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74598136;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=rs74598136" 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=rs74598136" 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=RCV000004568" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004568" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004568</a>
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<p>Extensive lytic lesions in the mandible of a 19-year-old Ashkenazi Jewish woman led <a href="#119" class="mim-tip-reference" title="Wasserstein, M. P., Martignetti, J. A., Zeitlin, R., Lumerman, H., Solomon, M., Grace, M. E., Desnick, R. J. <strong>Type 1 Gaucher disease presenting with extensive mandibular lytic lesions: identification and expression of a novel acid beta-glucosidase mutation.</strong> Am. J. Med. Genet. 84: 334-339, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10340647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10340647</a>]" pmid="10340647">Wasserstein et al. (1999)</a> to the diagnosis of type I Gaucher disease (<a href="/entry/230800">230800</a>). The patient had extensive skeletal involvement, marked hepatosplenomegaly, and deficient acid beta-glucosidase activity. Mutation analysis showed compound heterozygosity for 2 mutations in the GBA gene: an N370S mutation (<a href="#0003">606463.0003</a>) and a pro401-to-leu (P401L) substitution in exon 9. Expression of the P401L allele resulted in an enzyme with a reduced catalytic activity, which was similar to that of the mild N370S mutant enzyme. The expression studies predicted a mild phenotype for the proposita's N370S/P401L genotype, which was inconsistent with her severe diffuse skeletal disease and organ involvement. Since lytic mandibular lesions may be complicated by osteomyelitis, pathologic fractures, and tooth loss, <a href="#119" class="mim-tip-reference" title="Wasserstein, M. P., Martignetti, J. A., Zeitlin, R., Lumerman, H., Solomon, M., Grace, M. E., Desnick, R. J. <strong>Type 1 Gaucher disease presenting with extensive mandibular lytic lesions: identification and expression of a novel acid beta-glucosidase mutation.</strong> Am. J. Med. Genet. 84: 334-339, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10340647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10340647</a>]" pmid="10340647">Wasserstein et al. (1999)</a> suggested that regular dental assessments in type I Gaucher disease are warranted. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10340647" 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>.0037 GAUCHER DISEASE, PERINATAL LETHAL</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> rs78198234 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs78198234;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/rs78198234?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=rs78198234" 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=rs78198234" 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=RCV000004569 OR RCV001781180" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004569, RCV001781180" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004569...</a>
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<p>In 2 female sibs with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>), <a href="#101" class="mim-tip-reference" title="Stone, D. L., van Diggelen, O. P., de Klerk, J. B. C., Gaillard, J. L. J., Niermeijer, M. F., Willemsen, R., Tayebi, N., Sidransky, E. <strong>Is the perinatal lethal form of Gaucher disease more common than classic type 2 Gaucher disease?</strong> Europ. J. Hum. Genet. 7: 505-509, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352942</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10352942">Stone et al. (1999)</a> identified a homozygous mutation in exon 8 of the GBA gene, resulting in a his311-to-arg (H311R) substitution. The older sib was hydropic and delivered dead at 31 weeks' gestation. The second infant was hydropic and delivered alive at 30 weeks' gestation but died shortly after birth. The parents were a consanguineous couple from Cape Verde. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352942" 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>.0038 GAUCHER DISEASE, PERINATAL LETHAL</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> rs121908309 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908309;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/rs121908309?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=rs121908309" 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=rs121908309" 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=RCV000004570 OR RCV000585360 OR RCV000780288 OR RCV001249081 OR RCV002490309" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004570, RCV000585360, RCV000780288, RCV001249081, RCV002490309" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004570...</a>
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<p>In a male infant with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>), <a href="#101" class="mim-tip-reference" title="Stone, D. L., van Diggelen, O. P., de Klerk, J. B. C., Gaillard, J. L. J., Niermeijer, M. F., Willemsen, R., Tayebi, N., Sidransky, E. <strong>Is the perinatal lethal form of Gaucher disease more common than classic type 2 Gaucher disease?</strong> Europ. J. Hum. Genet. 7: 505-509, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352942</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10352942">Stone et al. (1999)</a> identified compound heterozygosity for 2 mutations in the GBA gene: a mutation in exon 8 resulting in an arg359-to-ter (R359X) substitution, and a mutation in exon 9 resulting in a val398-to-phe (V398F) substitution (<a href="#0039">606463.0039</a>). The patient's father was from Surinam and his mother was Dutch. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352942" 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>.0039 GAUCHER DISEASE, PERINATAL LETHAL</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> rs121908310 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908310;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/rs121908310?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=rs121908310" 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=rs121908310" 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=RCV000004544" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004544" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004544</a>
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<p>For discussion of the mutation in exon 9 of the GBA gene, resulting in a val398-to-phe (V398F) substitution, that was found in compound heterozygous state in a male infant with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>) by <a href="#101" class="mim-tip-reference" title="Stone, D. L., van Diggelen, O. P., de Klerk, J. B. C., Gaillard, J. L. J., Niermeijer, M. F., Willemsen, R., Tayebi, N., Sidransky, E. <strong>Is the perinatal lethal form of Gaucher disease more common than classic type 2 Gaucher disease?</strong> Europ. J. Hum. Genet. 7: 505-509, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352942</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10352942">Stone et al. (1999)</a>, see <a href="#0038">606463.0038</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352942" 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>.0040 GAUCHER DISEASE, TYPE I</strong>
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GAUCHER DISEASE, TYPE III, INCLUDED
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GBA, GLY377SER
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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> rs121908311 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908311;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/rs121908311?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=rs121908311" 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=rs121908311" 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=RCV000004571 OR RCV000004572 OR RCV000055772 OR RCV000723428 OR RCV001004116 OR RCV001270486 OR RCV002482828" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004571, RCV000004572, RCV000055772, RCV000723428, RCV001004116, RCV001270486, RCV002482828" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004571...</a>
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<p>In 3 Portuguese patients with type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#4" class="mim-tip-reference" title="Amaral, O., Lacerda, L., Marcao, A., Pinto, E., Tamagnini, G., Sa Miranda, M. C. <strong>Homozygosity for two mild glucocerebrosidase mutations of probable Iberian origin. (Letter)</strong> Clin. Genet. 56: 100-102, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10466427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10466427</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1999.560117.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10466427">Amaral et al. (1999)</a> identified homozygosity for a gly377-to-ser (G377S) substitution in the GBA gene. All 3 had mild to moderate severity with severity score indices (SSI), as defined by <a href="#125" class="mim-tip-reference" title="Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E. <strong>Prediction of severity of Gaucher's disease by identification of mutations at DNA level.</strong> Lancet 334: 349-352, 1989. Note: Originally Volume 2.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569551</a>] [<a href="https://doi.org/10.1016/s0140-6736(89)90536-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2569551">Zimran et al. (1989)</a>, of 8, 14, and 10, respectively. One of them had had splenectomy at age 9; the other 2 had recognized onset at ages 39 and 48 years. G377S seems to be common in Iberian patients, representing 7% and 5% of alleles in Portuguese and Spanish patients, respectively, according to <a href="#4" class="mim-tip-reference" title="Amaral, O., Lacerda, L., Marcao, A., Pinto, E., Tamagnini, G., Sa Miranda, M. C. <strong>Homozygosity for two mild glucocerebrosidase mutations of probable Iberian origin. (Letter)</strong> Clin. Genet. 56: 100-102, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10466427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10466427</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1999.560117.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10466427">Amaral et al. (1999)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10466427+2569551" 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="#79" class="mim-tip-reference" title="Park, J. K., Orvisky, E., Tayebi, N., Kaneski, C., Lamarca, M. E., Stubblefield, B. K., Martin, B. M., Schiffmann, R., Sidransky, E. <strong>Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup.</strong> Pediat. Res. 53: 387-395, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12595585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12595585</a>] [<a href="https://doi.org/10.1203/01.PDR.0000049515.79882.94" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12595585">Park et al. (2003)</a> identified a heterozygous G377S mutation in patients with type III Gaucher disease (<a href="/entry/231000">231000</a>); they had additional pathogenic GBA mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12595585" 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>.0041 GAUCHER DISEASE, PERINATAL LETHAL</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> rs78973108 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs78973108;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/rs78973108?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=rs78973108" 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=rs78973108" 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=RCV000004573 OR RCV000020159 OR RCV000079357 OR RCV000762855 OR RCV001004125 OR RCV001836699 OR RCV003225017 OR RCV004554584" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004573, RCV000020159, RCV000079357, RCV000762855, RCV001004125, RCV001836699, RCV003225017, RCV004554584" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004573...</a>
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<p>For discussion of the arg257-to-glu (R257E) mutation in the GBA gene that was found in compound heterozygous state in a preterm infant with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>) by <a href="#99" class="mim-tip-reference" title="Stone, D. L., Carey, W. F., Christodoulou, J., Sillence, D., Nelson, P., Callahan, M., Tayebi, N., Sidransky, E. <strong>Type 2 Gaucher disease: the collodion baby phenotype revisited.</strong> Arch. Dis. Child. Fetal Neonatal Ed. 82: F163-F166, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10685993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10685993</a>] [<a href="https://doi.org/10.1136/fn.82.2.f163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10685993">Stone et al. (2000)</a>, see <a href="#0023">606463.0023</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10685993" 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>.0042 GAUCHER DISEASE, PERINATAL LETHAL</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> rs80356763 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356763;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/rs80356763?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=rs80356763" 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=rs80356763" 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=RCV000004574 OR RCV000020155" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004574, RCV000020155" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004574...</a>
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<p>In a sib pair with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>), born to Mexican parents, <a href="#99" class="mim-tip-reference" title="Stone, D. L., Carey, W. F., Christodoulou, J., Sillence, D., Nelson, P., Callahan, M., Tayebi, N., Sidransky, E. <strong>Type 2 Gaucher disease: the collodion baby phenotype revisited.</strong> Arch. Dis. Child. Fetal Neonatal Ed. 82: F163-F166, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10685993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10685993</a>] [<a href="https://doi.org/10.1136/fn.82.2.f163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10685993">Stone et al. (2000)</a> detected homozygosity for a mutation in the GBA gene resulting in an arg131-to-leu (R131L) substitution. The parents were unaware of any common ancestry, and genetic studies to confirm or refute consanguinity were not possible. The first-born was a male infant with collodion skin at birth which improved within 2 weeks. He subsequently developed rapidly progressive neurologic disease and died at 7 months. Fibroblast glucocerebrosidase activity was 3% of control values. His sister was diagnosed by prenatal enzyme assay and was born at 37 weeks' gestation with collodion skin and hepatosplenomegaly. Her skin condition resolved during the first month of life, but she developed neurologic abnormalities and died at age 9 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10685993" 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>.0043 GAUCHER DISEASE, TYPE I</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">rs121908312 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908312;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=rs121908312" 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=rs121908312" 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=RCV000004575 OR RCV000004576 OR RCV000790694 OR RCV002281694" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004575, RCV000004576, RCV000790694, RCV002281694" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004575...</a>
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<p><a href="#121" class="mim-tip-reference" title="Zhao, H., Bailey, L. A., Elsas, L. J., II, Grinzaid, K. A., Grabowski, G. A. <strong>Gaucher disease: in vivo evidence for allele dose leading to neuronopathic and nonneuronopathic phenotypes.</strong> Am. J. Med. Genet. 116A: 52-56, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12476451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12476451</a>] [<a href="https://doi.org/10.1002/ajmg.a.10029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12476451">Zhao et al. (2003)</a> described a 57-year-old woman of Cherokee ancestry with Gaucher disease type I (<a href="/entry/230800">230800</a>) who was homozygous for a 2855G-C transversion in exon 4 of the GBA gene causing a lys79-to-asn (K79N) substitution. They also described a 2-year-old male of Caucasian/Cherokee ancestry with Gaucher disease type III (<a href="/entry/231000">231000</a>) who was a compound heterozygote for the same K79N allele and a novel complex mutation (null allele). The K79N allele was identical in the 2 cases as determined by complete gene sequencing, suggesting a founder effect. The discrepant phenotypes (Gaucher disease types I and III) in these 2 patients provided support for a threshold of residual activity necessary to 'protect' the CNS from the pathogenic effects of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12476451" 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>.0044 GAUCHER DISEASE, PERINATAL LETHAL</strong>
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GBA, PHE251LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908313 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908313;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=rs121908313" 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=rs121908313" 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=RCV000004577" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004577" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004577</a>
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<p>In an infant with the perinatal lethal variant of Gaucher disease (<a href="/entry/608013">608013</a>), <a href="#122" class="mim-tip-reference" title="Zhao, H., Keddache, M., Bailey, L., Arnold, G. L., Grabowski, G. <strong>Gaucher's disease: identification of novel mutant alleles and genotype-phenotype relationships.</strong> Clin. Genet. 64: 57-64, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12791040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12791040</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00100.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12791040">Zhao et al. (2003)</a> described compound heterozygosity for 2 mutations in the GBA gene: IVS2+1G-A (<a href="#0015">606463.0015</a>) and a 5101C-A transversion resulting in a phe251-to-leu (F251L) substitution. Both enzyme activity and protein were greatly decreased in cultured skin fibroblasts. After birth, the patient was noted to have absent respiratory effort, tight shiny skin, a heart murmur, and frequent myoclonic jerks and died at age 1 month due to respiratory failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12791040" 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>.0045 GAUCHER DISEASE, TYPE I</strong>
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GBA, LEU371VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908314 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908314;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=rs121908314" 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=rs121908314" 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=RCV000004578" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004578" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004578</a>
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<p>In 6 affected members in 3 generations of a consanguineous Lebanese family with moderately severe type I Gaucher disease (<a href="/entry/230800">230800</a>), <a href="#91" class="mim-tip-reference" title="Shamseddine, A., Taher, A., Fakhani, S., Zhang, M., Scott, C. R., Habbal, M. Z. <strong>Novel mutation, L371V, causing multigenerational Gaucher disease in a Lebanese family.</strong> Am. J. Med. Genet. 125A: 257-260, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14994233/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14994233</a>] [<a href="https://doi.org/10.1002/ajmg.a.20518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14994233">Shamseddine et al. (2004)</a> identified homozygosity for a 1228C-G transversion in the GBA gene, resulting in a leu371-to-val (L371V) mutation. The disorder was more severe than that observed with the common N370S (<a href="#0003">606463.0003</a>) mutation associated with type I Gaucher disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14994233" 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>.0046 GAUCHER DISEASE, PERINATAL LETHAL</strong>
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GBA, IVS10DS, G-A, -1
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1571964338 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1571964338;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=rs1571964338" 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=rs1571964338" 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=RCV000004579" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004579" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004579</a>
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<p>In a premature infant with perinatal lethal Gaucher disease (<a href="/entry/608013">608013</a>), <a href="#30" class="mim-tip-reference" title="Felderhoff-Mueser, U., Uhl, J., Penzel, R., van Landeghem, F., Vogel, M., Obladen, M., Kopitz, J. <strong>Intrauterine onset of acute neuropathic type 2 Gaucher disease: identification of a novel insertion sequence.</strong> Am. J. Med. Genet. 128A: 138-143, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15214004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15214004</a>] [<a href="https://doi.org/10.1002/ajmg.a.20445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15214004">Felderhoff-Mueser et al. (2004)</a> identified compound heterozygosity for the R120Q mutation (<a href="#0004">606463.0004</a>) and a G-to-A substitution at the first position in the splice site of intron 10 of the GBA gene, resulting in the insertion of the first 11 basepairs of IVS10 and deletion of the first 11 basepairs of exon 11. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15214004" 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>.0047 GAUCHER DISEASE, TYPE II</strong>
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GAUCHER DISEASE, TYPE III, INCLUDED
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GBA, HIS255GLN AND ASP409HIS
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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> rs1064651 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1064651;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/rs1064651?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=rs1064651" 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=rs1064651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <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> rs367968666 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs367968666;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/rs367968666?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=rs367968666" 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=rs367968666" 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=RCV000004522 OR RCV000004523 OR RCV000004524 OR RCV000004525 OR RCV000004526 OR RCV000004580 OR RCV000004581 OR RCV000055773 OR RCV000079338 OR RCV000589369 OR RCV000762853 OR RCV001004114 OR RCV001004126 OR RCV001195955 OR RCV001248861 OR RCV001329068 OR RCV001836695 OR RCV002247685 OR RCV004018557 OR RCV004751398" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004522, RCV000004523, RCV000004524, RCV000004525, RCV000004526, RCV000004580, RCV000004581, RCV000055773, RCV000079338, RCV000589369, RCV000762853, RCV001004114, RCV001004126, RCV001195955, RCV001248861, RCV001329068, RCV001836695, RCV002247685, RCV004018557, RCV004751398" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004522...</a>
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<p>In a 25-month-old girl with an atypical form of neuronopathic Gaucher disease between type II (<a href="/entry/230900">230900</a>) and type III (<a href="/entry/231000">231000</a>), <a href="#31" class="mim-tip-reference" title="Filocamo, M., Grossi, S., Stroppiano, M., Regis, S., Tortori-Donati, P., Allegri, A., Di Rocco, M. <strong>Homozygosity for a non-pseudogene complex glucocerebrosidase allele as cause of an atypical neuronopathic form of Gaucher disease. (Letter)</strong> Am. J. Med. Genet. 134A: 95-96, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15690354/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15690354</a>] [<a href="https://doi.org/10.1002/ajmg.a.30316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15690354">Filocamo et al. (2005)</a> identified homozygosity for a complex allele containing 2 GBA mutations in cis: an 882T-G transversion in exon 7 resulting in a his255-to-gln (H255Q) substitution and a 1342G-C transversion in exon 10 resulting in an asp409-to-his (D409H; <a href="#0006">606463.0006</a>) substitution. Onset of symptoms occurred at age 5 months with hepatosplenomegaly. A few months later, she developed neurologic features, including spasticity with persistent retroflexion of the neck, convergent strabismus, oculomotor apraxia, and abnormal MRI changes. At age 25 months, she showed slow symptom progression and was able to sit alone, walk with support, and pronounce some words. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15690354" 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>.0048 PARKINSON DISEASE, LATE-ONSET, SUSCEPTIBILITY TO</strong>
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GBA, ASP443ASN
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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> rs75671029 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75671029;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/rs75671029?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=rs75671029" 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=rs75671029" 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=RCV000004582 OR RCV001174737 OR RCV001582465 OR RCV001826414 OR RCV002490310" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004582, RCV001174737, RCV001582465, RCV001826414, RCV002490310" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004582...</a>
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<p>In 1 (0.13%) of 790 British patients with Parkinson disease (PD; <a href="/entry/168600">168600</a>), <a href="#74" class="mim-tip-reference" title="Neumann, J., Bras, J., Deas, E., O'Sullivan, S. S., Parkkinen, L., Lachmann, R. H., Li, A., Holton, J., Guerreiro, R., Paudel, R., Segarane, B., Singleton, A., Lees, A., Hardy, J., Houlden, H., Revesz, T., Wood, N. W. <strong>Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease.</strong> Brain 132: 1783-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286695</a>] [<a href="https://doi.org/10.1093/brain/awp044" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19286695">Neumann et al. (2009)</a> identified a heterozygous 1444G-A transition in exon 10 of the GBA gene, resulting in an asp443-to-asn (D443N) substitution. The mutation was not found in 257 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19286695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="seeAlso" class="mim-anchor"></a>
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<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<a href="#Dinur1986" class="mim-tip-reference" title="Dinur, T., Osiecki, K. M., Legler, G., Gatt, S., Desnick, R. J., Grabowski, G. A. <strong>Human acid beta-glucosidase: isolation and amino acid sequence of a peptide containing the catalytic site.</strong> Proc. Nat. Acad. Sci. 83: 1660-1664, 1986.">Dinur et al. (1986)</a>; <a href="#Grabowski1985" class="mim-tip-reference" title="Grabowski, G. A., Dinur, T., Osiecki, K. M., Kruse, J. R., Legler, G., Gatt, S. <strong>Gaucher disease types 1, 2, and 3: differential mutations of the acid beta-glucosidase active site identified with conduritol B epoxide derivatives and sphingosine.</strong> Am. J. Hum. Genet. 37: 499-510, 1985.">Grabowski et al. (1985)</a>; <a href="#Graves1986" class="mim-tip-reference" title="Graves, P. N., Grabowski, G. A., Ludman, M. D., Palese, P., Smith, F. I. <strong>Human acid beta-glucosidase: Northern blot and S1 nuclease analysis of mRNA from HeLa cells and normal and Gaucher disease fibroblasts.</strong> Am. J. Hum. Genet. 39: 763-774, 1986.">Graves et al. (1986)</a>
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<a id="Abrahamov1995" class="mim-anchor"></a>
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Abrahamov, A., Elstein, D., Gross-Tsur, V., Farber, B., Glaser, Y., Hadas-Halpern, I., Ronen, S., Tafakjdi, M., Horowitz, M., Zimram, A.
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<strong>Gaucher's disease variant characterized by progressive calcification of heart valves and unique genotype.</strong>
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Lancet 346: 1000-1003, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7475546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7475546</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7475546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(95)91688-1" target="_blank">Full Text</a>]
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Aharon-Peretz, J., Badarny, S., Rosenbaum, H., Gershoni-Baruch, R.
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<strong>Mutations in the glucocerebrosidase gene and Parkinson disease: phenotype-genotype correlation.</strong>
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Neurology 65: 1460-1461, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16148263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16148263</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16148263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000176987.47875.28" target="_blank">Full Text</a>]
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Aharon-Peretz, J., Rosenbaum, H., Gershoni-Baruch, R.
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<strong>Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.</strong>
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New Eng. J. Med. 351: 1972-1977, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15525722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15525722</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15525722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMoa033277" target="_blank">Full Text</a>]
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Amaral, O., Lacerda, L., Marcao, A., Pinto, E., Tamagnini, G., Sa Miranda, M. C.
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<strong>Homozygosity for two mild glucocerebrosidase mutations of probable Iberian origin. (Letter)</strong>
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Clin. Genet. 56: 100-102, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10466427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10466427</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10466427" 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/10.1034/j.1399-0004.1999.560117.x" target="_blank">Full Text</a>]
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Barneveld, R. A., Keijzer, W., Tegelaers, F. P. W., Ginns, E. I., Geurts van Kessel, A., Brady, R. O., Barranger, J. A., Tager, J. M., Galjaard, H., Westerveld, A., Reuser, A. J. J.
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<strong>Assignment of the gene coding for human beta-glucocerebrosidase to the region q21-q31 of chromosome 1 using monoclonal antibodies.</strong>
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Hum. Genet. 64: 227-231, 1983.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6885065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6885065</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6885065" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00279398" target="_blank">Full Text</a>]
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<a id="Beutler1994" class="mim-anchor"></a>
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Beutler, E., Demina, A., Gelbart, T.
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<strong>Glucocerebrosidase mutations in Gaucher disease.</strong>
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Molec. Med. 1: 82-92, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8790604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8790604</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8790604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Beutler1995" class="mim-anchor"></a>
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Beutler, E., Gelbart, T., Demina, A., Zimran, A., LeCoutre, P.
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<strong>Five new Gaucher disease mutations.</strong>
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Blood Cells Molec. Dis. 21: 20-24, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7655857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7655857</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7655857" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/bcmd.1995.0004" target="_blank">Full Text</a>]
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<a id="Beutler1991" class="mim-anchor"></a>
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Beutler, E., Gelbart, T., Kuhl, W., Sorge, J., West, C.
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<strong>Identification of the second common Jewish Gaucher disease mutation makes possible population-based screening for the heterozygous state.</strong>
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Proc. Nat. Acad. Sci. 88: 10544-10547, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1961718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1961718</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1961718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.88.23.10544" target="_blank">Full Text</a>]
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<a id="Beutler1992" class="mim-anchor"></a>
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Beutler, E., Gelbart, T., Kuhl, W., Zimran, A., West, C.
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<strong>Mutations in Jewish patients with Gaucher disease.</strong>
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Blood 79: 1662-1666, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1558964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1558964</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1558964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Beutler, E., Gelbart, T., West, C.
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<strong>Identification of six new Gaucher disease mutations.</strong>
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Genomics 15: 203-205, 1993.
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[<a href="https://doi.org/10.1006/geno.1993.1035" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1469-1809.1990.tb00371.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)8:3<207::AID-HUMU2>3.0.CO;2-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.1589760" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.90.12.5384" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/wnl.54.1.261" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.32.9.740" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<295::AID-HUMU7>3.0.CO;2-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s004390050468" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/302946" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17954912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17954912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17954912[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=17954912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0708086104" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00200914" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0378-1119(90)90264-r" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.20445" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30316" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/brain/awp161" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000304039.11891.29" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/301969" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.82.20.7101" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000230215.41296.18" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.2004.024455" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/cge.12084" target="_blank">Full Text</a>]
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<strong>Gaucher disease types 1, 2, and 3: differential mutations of the acid beta-glucosidase active site identified with conduritol B epoxide derivatives and sphingosine.</strong>
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[<a href="https://doi.org/10.1172/JCI5168" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI119437" target="_blank">Full Text</a>]
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<strong>Gaucher disease type I: cloning and characterization of a cDNA encoding acid beta-glucosidase from an Ashkenazi Jewish patient.</strong>
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[<a href="https://doi.org/10.1089/dna.1.1988.7.521" target="_blank">Full Text</a>]
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<a id="Graves1986" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1172/JCI114818" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.84.4.906" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.82.21.7289" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/fn.82.2.f163" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/357407a0" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1600-0404.1992.tb05109.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.34.2.175" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/icb.1979.56" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI116276" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8487270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8487270</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8487270" 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.30.4.280" target="_blank">Full Text</a>]
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Zhao, H., Bailey, L. A., Elsas, L. J., II, Grinzaid, K. A., Grabowski, G. A.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12476451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12476451</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12476451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.10029" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1034/j.1399-0004.2003.00100.x" target="_blank">Full Text</a>]
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Zimran, A., Gelbart, T., Beutler, E.
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<strong>Linkage of the PvuII polymorphism with the common Jewish mutation for Gaucher disease.</strong>
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Zimran, A., Gelbart, T., Westwood, B., Grabowski, G. A., Beutler, E.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1897529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1897529</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1897529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E.
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<strong>Prediction of severity of Gaucher's disease by identification of mutations at DNA level.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569551</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2569551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(89)90536-9" target="_blank">Full Text</a>]
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Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E.
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<strong>A glucocerebrosidase fusion gene in Gaucher disease: implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2295698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2295698</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2295698" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI114415" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Bao Lige - updated : 06/13/2018
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<span class="mim-text-font">
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George E. Tiller - updated : 06/21/2017<br>Paul J. Converse - updated : 02/05/2016<br>Cassandra L. Kniffin - updated : 11/5/2013<br>Patricia A. Hartz - updated : 8/7/2013<br>Cassandra L. Kniffin - updated : 4/22/2013<br>Patricia A. Hartz - updated : 2/28/2012<br>Cassandra L. Kniffin - updated : 6/13/2011<br>Cassandra L. Kniffin - updated : 2/19/2010<br>Cassandra L. Kniffin - updated : 11/4/2009<br>Marla J. F. O'Neill - updated : 6/8/2009<br>Cassandra L. Kniffin - updated : 3/16/2009<br>Cassandra L. Kniffin - updated : 10/8/2008<br>Cassandra L. Kniffin - updated : 8/25/2008<br>Cassandra L. Kniffin - updated : 8/12/2008<br>Cassandra L. Kniffin - updated : 4/2/2008<br>Cassandra L. Kniffin - updated : 8/3/2007<br>Cassandra L. Kniffin - updated : 2/19/2007<br>Cassandra L. Kniffin - reorganized : 11/2/2006<br>Cassandra L. Kniffin - updated : 10/2/2006<br>Cassandra L. Kniffin - updated : 4/20/2006<br>Cassandra L. Kniffin - updated : 1/24/2005<br>Marla J. F. O'Neill - updated : 7/20/2004<br>Victor A. McKusick - updated : 6/15/2004<br>Victor A. McKusick - updated : 4/6/2004<br>Victor A. McKusick - updated : 7/18/2003<br>Victor A. McKusick - updated : 2/28/2003<br>Victor A. McKusick - updated : 1/31/2003<br>Victor A. McKusick - updated : 8/19/2002<br>Victor A. McKusick - updated : 5/9/2002
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Ada Hamosh : 11/16/2001
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carol : 06/18/2022
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carol : 04/28/2022<br>alopez : 03/08/2022<br>carol : 09/04/2020<br>carol : 07/20/2020<br>carol : 05/13/2020<br>carol : 05/11/2020<br>mgross : 06/13/2018<br>mgross : 06/13/2018<br>alopez : 06/21/2017<br>mgross : 02/05/2016<br>mcolton : 3/19/2015<br>mcolton : 2/24/2014<br>joanna : 2/20/2014<br>carol : 11/6/2013<br>ckniffin : 11/5/2013<br>carol : 10/22/2013<br>carol : 9/16/2013<br>mgross : 8/7/2013<br>alopez : 5/1/2013<br>ckniffin : 4/22/2013<br>terry : 3/28/2013<br>carol : 3/8/2013<br>terry : 11/15/2012<br>mgross : 6/5/2012<br>mgross : 6/5/2012<br>terry : 2/28/2012<br>wwang : 6/22/2011<br>ckniffin : 6/13/2011<br>alopez : 3/24/2011<br>ckniffin : 11/17/2010<br>wwang : 2/19/2010<br>ckniffin : 2/19/2010<br>carol : 11/11/2009<br>ckniffin : 11/4/2009<br>wwang : 6/24/2009<br>terry : 6/8/2009<br>terry : 4/13/2009<br>wwang : 3/25/2009<br>ckniffin : 3/16/2009<br>wwang : 2/9/2009<br>ckniffin : 2/3/2009<br>wwang : 1/12/2009<br>wwang : 10/15/2008<br>ckniffin : 10/8/2008<br>wwang : 9/18/2008<br>ckniffin : 8/25/2008<br>wwang : 8/22/2008<br>ckniffin : 8/12/2008<br>wwang : 4/10/2008<br>ckniffin : 4/2/2008<br>wwang : 8/17/2007<br>ckniffin : 8/3/2007<br>wwang : 2/22/2007<br>ckniffin : 2/19/2007<br>ckniffin : 11/3/2006<br>carol : 11/2/2006<br>ckniffin : 11/1/2006<br>wwang : 10/6/2006<br>ckniffin : 10/2/2006<br>ckniffin : 10/2/2006<br>wwang : 4/26/2006<br>ckniffin : 4/20/2006<br>wwang : 1/10/2006<br>ckniffin : 1/3/2006<br>carol : 11/18/2005<br>carol : 6/14/2005<br>tkritzer : 1/27/2005<br>ckniffin : 1/24/2005<br>carol : 8/26/2004<br>carol : 7/21/2004<br>terry : 7/20/2004<br>tkritzer : 6/22/2004<br>terry : 6/15/2004<br>tkritzer : 4/14/2004<br>terry : 4/6/2004<br>tkritzer : 8/20/2003<br>cwells : 7/29/2003<br>terry : 7/18/2003<br>tkritzer : 3/7/2003<br>tkritzer : 3/5/2003<br>terry : 2/28/2003<br>tkritzer : 2/3/2003<br>terry : 1/31/2003<br>tkritzer : 8/19/2002<br>alopez : 5/14/2002<br>terry : 5/9/2002<br>ckniffin : 5/7/2002<br>mgross : 4/8/2002<br>carol : 11/29/2001<br>terry : 11/29/2001<br>terry : 11/28/2001<br>terry : 11/19/2001<br>terry : 11/19/2001<br>carol : 11/16/2001
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606463
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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GLUCOSIDASE, BETA, ACID; GBA
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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GBA1<br />
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ACID BETA-GLUCOSIDASE<br />
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BETA-GLUCOSIDASE, ACID<br />
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BETA-GC<br />
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GLUCOCEREBROSIDASE<br />
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GLUCOSYLCERAMIDASE
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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GLUCOCEREBROSIDASE PSEUDOGENE, INCLUDED; GBAP, INCLUDED
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GBA1</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 12246008, 5963005, 62201009, 870313002;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 1q22
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:155,234,452-155,244,627 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="7">
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<span class="mim-font">
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1q22
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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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{Lewy body dementia, susceptibility to}
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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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127750
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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{Parkinson disease, late-onset, susceptibility to}
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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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168600
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Multifactorial
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Gaucher disease, perinatal lethal
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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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608013
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Gaucher disease, type I
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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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230800
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Gaucher disease, type II
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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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230900
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Gaucher disease, type III
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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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231000
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Gaucher disease, type IIIC
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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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231005
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Acid beta-glucocerebrosidase, also known as beta-glucosidase (GBA; EC 3.2.1.45), is a lysosomal enzyme that catalyzes the breakdown of the glycolipid glucosylceramide (GlcCer) to ceramide and glucose (Beutler, 1992). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Sorge et al. (1985) isolated and characterized a cDNA clone corresponding to the human beta-glucosidase gene from a human cDNA library. Using the ATG at positions 154-156 as the correct initiator codon, the deduced protein is 515 amino acids long and contains a 19-amino acid signal sequence. The mature 496-residue protein has a calculated molecular mass of 55.4 kD. The cDNA directed the synthesis of functional glucocerebrosidase when expressed in mammalian cells. </p><p>Tsuji et al. (1986) isolated GBA cDNA clones from a human hepatoma cDNA library. The deduced 516-residue protein has a calculated molecular mass of 57 kD. </p><p>Sorge et al. (1987) demonstrated that human GBA cDNA contains 2 potential ATG start codons, with the upstream ATG resulting in a protein with a 39-amino acid signal peptide and the downstream ATG resulting in a protein with a 19-amino acid signal peptide. The corresponding signal peptides differed in their hydrophobicity. Either ATG could function to produce active enzyme in cultured fibroblasts. Functional enzyme activity from either translation products was found predominantly in lysosomes. </p><p>Reiner et al. (1988) isolated 2 different genomic clones encoding human GBA from a fetal liver library. These clones represented 2 glucocerebrosidase genes, which the authors designated 6-1 and 10-2. The second gene is a putative pseudogene (see below). Both genes had identifiable promoter regions, but the promoter of gene 6-1 was much more efficient than that for gene 10-2 in a chloramphenicol acetyltransferase assay. Reiner et al. (1988) stated that both genes appear to be mapped at the same locus (Choudary et al., 1986). </p><p>Horowitz et al. (1989) identified 2 GBA mRNA species: a major 2.6-kb transcript and a minor 2.2-kb transcript. </p><p>O'Neill et al. (1989) found that the human and mouse GBA amino acid sequences share 86% identity. All 5 amino acids known to be essential for normal enzymatic activity are conserved between mouse and man. Only 1 ATG translation initiation signal was present in the mouse sequence, whereas 2 have been reported in the human sequence. </p><p><strong><em>Pseudogene</em></strong></p><p>
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Horowitz et al. (1989) sequenced a GBA pseudogene, which is 96% homologous to the functional gene. Compared to the functional gene, the pseudogene has large deletions within several introns, representing Alu sequences flanked by direct repeats, as well as base pair changes scattered throughout the gene. Reiner and Horowitz (1988) found that the promoter of the glucocerebrosidase pseudogene has demonstrable activity when attached to a reporter gene. They commented that mutations in the rest of the gene must render the mRNA vulnerable to breakdown or other functional abnormality such that no enzyme is synthesized. </p><p>By studies of RNA from lymphoblasts and fibroblasts from patients with Gaucher disease (see 230800) and normal subjects, Sorge et al. (1990) found that the pseudogene was consistently transcribed and that in some cases the level of transcription seemed to be approximately equal to that of the functional gene. The mouse genome did not appear to contain the pseudogene. </p><p>Tayebi et al. (1996) reported a method to distinguish the glucocerebrosidase gene from the pseudogene, which is 2 kb shorter than the expressed gene. The technique involved the use of long-template PCR and PCR primers to simultaneously generate a 5.6-kb fragment from the functional glucocerebrosidase gene and a 3.9-kb fragment from the pseudogene. The PCR products were then individually purified and used in subsequent experiments for mutation detection. </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>Horowitz et al. (1989) determined that the GBA gene contains 11 exons. </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>Shafit-Zagardo et al. (1981) assigned the GBA gene to chromosome 1p11-qter. Devine et al. (1982) narrowed the assignment to 1q42-qter. By study of hamster-human somatic cell hybrids, Barneveld et al. (1983) assigned GBA to 1q21-q31, which was consistent with the studies of Shafit-Zagardo et al. (1981) but not with those of Devine et al. (1982). Three studies suggested localization of the GBA gene in distal 1q31 or proximal subband 1q32.1 (Philip et al., 1985). By somatic cell hybridization and in situ hybridization, Ginns et al. (1985) placed GBA at 1q21. </p><p>Cormand et al. (1997) used an intragenic polymorphism of the GBA gene (6144A-G) to localize GBA in relation to markers in the Genethon human linkage map and to a 3.2-cM interval at chromosome 1q21. No recombination was found between 6 markers and the GBA gene. Three of the markers, D1S2777, D1S303, and D1S2140, are present in YAC clone 887h8 which also contains the GBA gene and the PKLR gene (609712). Mateu et al. (2002) found complete linkage disequilibrium in the PKLR-GBA region over 70 kb in a set of worldwide populations. Variation at PKLR-GBA was also tightly linked to that at the GBA pseudogene. Thus, a 90-kb linkage disequilibrium block was observed, which points to a low recombination rate in this region. </p><p>By linkage studies of interspecific backcrosses of Mus spretus and Mus musculus domesticus, Seldin (1989) demonstrated that the Gba gene is located on mouse chromosome 3. O'Neill et al. (1989) pointed out that although the NGFB (162030) and GBA loci are syntenic in both mouse and the human (they are about 7.6 cM apart on mouse chromosome 3), they represent a conserved segment that spans the centromere in man. </p><p><strong><em>Pseudogene</em></strong></p><p>
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The GBA pseudogene is located approximately 16 kb downstream from GBA (Sorge et al., 1990). </p><p>Zimran et al. (1989) identified a new mutation which represented crossing-over between the GBA gene and the pseudogene, resulting in a fusion gene designated 'XOVR.' Zimran et al. (1990) reported that this 'Lepore-like' glucocerebrosidase fusion gene consisted of the 5-prime end of the functional gene and the 3-prime end of the pseudogene. The location of a pseudogene near the functional gene for GBA on chromosome 1q may be the basis of disease-producing changes in the functional gene through gene conversion, similar to what occurs with the CYP21 gene (613815) on 6p (Horowitz, 1990). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene 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>Reczek et al. (2007) found that LIMP2 (SCARB2; 602257) bound beta-GC, but not alpha-galactosidase (GLA; 300644) or alpha-glucosidase (GAA; 606800). Beta-GC and LIMP2 interacted in the endoplasmic reticulum, and both proteins traversed the Golgi and endocytic compartments together en route to lysosomes. In vitro, low pH attenuated binding between the 2 proteins, suggesting that acidic lysosomal pH facilitates dissociation of beta-GC from LIMP2. Cross-linking experiments with transfected COS cells suggested that the beta-GC-LIMP2 complex is about 250 kD in size, consistent with a 2:2 beta-GC:LIMP2 stoichiometry. Mutation analysis revealed that a coiled-coil motif within the luminal domain of LIMP2 was required for beta-GC binding. Knockdown of LIMP2 in HeLa cells via small interfering RNA significantly reduced lysosomal beta-GC content and resulted in mistargeting of beta-GC for secretion. Limp2 knockout in mice significantly reduced beta-GC content in liver and kidney, but had no effect on beta-GC mRNA. Limp2 -/- mice, but not wildtype mice, showed elevated serum beta-GC and increased GlcCer content in liver and lung, but not in kidney, spleen, and brain. Limp2 -/- mice did not show a robust Gaucher-like phenotype. Reczek et al. (2007) concluded that LIMP2 functions as a mannose-6-phosphate-independent receptor for lysosomal targeting of beta-GC. </p><p>An association between Gaucher disease and Parkinson disease (PD; 168600; see MOLECULAR GENETICS) has been demonstrated by the concurrence of PD in some Gaucher disease patients and the identification of GBA mutations in some probands with sporadic PD. Ron et al. (2010) showed that mutant GBA variants associated with parkin (PARK2; 602544), and that wildtype parkin, but not its RING finger mutants, affected the stability of mutant GBA variants. Parkin also promoted the accumulation of mutant GBA in aggresome-like structures and was involved in lys48 (K48)-mediated polyubiquitination of GBA mutants, thus indicating its function as an E3 ligase. The authors suggested that involvement of parkin in the degradation of mutant GBA may explain the concurrence of Gaucher disease and PD. </p><p>Jovic et al. (2012) found that PI4KII-alpha (PI4K2A; 609763) and PI4KIII-beta (PI4KB; 602758), both of which synthesize phosphatidylinositol-4-phosphate (PtdIns4P), had distinct and sequential roles in the lysosomal delivery of beta-GC and LIMP2. Activity of PI4KIII-beta at the Golgi was required to drive exit of LIMP2 from the Golgi, whereas PI4KII-alpha at the trans-Golgi network regulated sorting of LIMP2 toward the late endosome/lysosome compartment. Knockdown or inhibition of PI3KIII-beta led to accumulation of LIMP2 at the Golgi compartment, and knockdown of either LIMP2 or PI4KII-alpha increased beta-GC secretion. Mutations in PI4KII-alpha that disrupted its association with AP3 (see AP3B1, 603401) disrupted lysosomal LIMP2 targeting. </p><p>By combining genetic perturbation of sphingolipid metabolism with quantification of TLR (see 601194) signaling steps and mass spectrometry-based lipidomics in mouse cells, Koberlin et al. (2015) uncovered a circular network of coregulated sphingolipids and glycerophospholipids. Quantitative lipidomics on fibroblasts from patients with mutations in GBA, GALC (606890), ASAH1 (613468), or LYST (606897) revealed conservation of the circular organization of lipid coregulation across species, cell types, and genetic perturbations. The functional annotation accurately predicted TLR-mediated inflammatory responses, in terms of changes in lipid abundance and lipid species, in patient cells. </p><p>Panicker et al. (2018) found that GBA1 deficiency did not appear to interfere with the ability of induced pluripotent stem cells (iPSCs) from Gaucher disease (GD; see 230800) patients to differentiate efficiently to mesenchymal stem cells (MSCs), but that it did interfere with differentiation from MSCs to osteoblasts and osteoblast bone-forming ability. GD iPSC osteoblasts had defective Wnt/beta-catenin signaling by mutant GBA1, which likely contributed to the defect in GD osteoblast differentiation. GD osteoblast differentiation could be restored by treatment with a potent inhibitor of GSK3-beta (605004). Assessment of the integrity of the lysosomal compartment in GD osteoblasts showed that mutant GBA1 had deleterious effects on the osteoblast lysosomal compartment, as Ca(2+)-dependent exocytosis, a lysosomal function critically required for bone matrix deposition, was significantly impaired. Furthermore, the lysosomal compartment in GD iPSC osteoblasts had defects in plasma membrane repair, another lysosome-dependent function important for osteoblast survival. </p>
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<h4>
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<strong>Molecular Genetics</strong>
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<p>The numbering system used for some of the mutations in the MOLECULAR GENETICS and ALLELIC VARIANTS sections in this entry is based on the mature GBA protein and does not include the 39-residue signal peptide.</p><p><strong><em>Gaucher Disease, Types I, II, and III</em></strong></p><p>
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Nearly 200 mutations in the GBA gene have been described in patients with Gaucher disease types I (GD1; 230800), II (GD2; 230900), and III (GD3; 231000) (Jmoudiak and Futerman, 2005). </p><p>Tsuji et al. (1987) identified a mutation in the GBA gene (L444P; 606463.0001) in patients with Gaucher disease types I, II, and III. Two of the 5 patients with type II and 7 of the 11 with type III were homozygous for this mutation, whereas 4 of 20 patients with type I Gaucher disease had this mutant allele in heterozygous state. The L444P substitution occurs naturally in the GBA pseudogene. </p><p>Latham et al. (1990) presented a useful diagram of 9 mutations in the GBA gene identified in patients with Gaucher disease. Four of the mutations (L444P; D409H; 606463.0006, A456P and V460V; 606463.0009) were known to be present also in the pseudogene. </p><p>Beutler (1993), Mistry and Cox (1993), Horowitz and Zimran (1994), Beutler et al. (1994), Beutler and Gelbart (1996), and Stone et al. (2000) provided updates on mutations in the GBA gene causing Gaucher disease. </p><p>In an analysis of 60 type I and type III Gaucher patients, Sidransky et al. (1994) found that the 5 most common Gaucher mutations, N370S (606463.0003), L444P, R463C (606463.0008), 84insG, (606463.0014) and IVS2+1G-A (606463.0015), were identified in patients with or without neurologic manifestations. The findings indicated that Gaucher patients sharing identical genotypes can exhibit considerable clinical heterogeneity. </p><p>Grace et al. (1997) identified 6 new pathogenic mutations in the GBA gene in 5 severely affected type I and type II Gaucher disease patients of non-Jewish descent. </p><p>Sidransky et al. (1996) described homozygosity for a triply mutant GBA allele (606463.0009) in 2 conceptuses from an Afghan family with perinatal lethal Gaucher disease (608013). The findings were comparable to those in the 'knockout' Gaucher mouse in which absence of enzyme was incompatible with long survival (Tybulewicz et al., 1992). In an infant with perinatal lethal Gaucher disease, Tayebi et al. (1997) identified homozygosity for a null mutation in the GBA gene (606463.0034). This case confirmed the essential role of GBA in human development. </p><p>Germain et al. (1998) described an exhaustive screening strategy, involving fluorescence-assisted mismatch analysis using universal primers, and succeeded in identifying both Gaucher disease mutant alleles in all 25 patients studied. A total of 18 different mutations and a new Gaucher disease haplotype were detected. </p><p>In a patient with perinatal lethal Gaucher disease, Grace et al. (1999) identified 2 pathogenic alleles in the GBA gene. Stone et al. (2000) reported 6 children who presented at birth with collodion-type skin changes and hepatosplenomegaly and were found to be beta-glucocerebrosidase-deficient. All died shortly after birth or in the first year of life from respiratory insufficiency or progressive neurologic disease. Three of the cases were homozygous for GBA mutations (see 606463.0009 and 606463.0042) and the others were compound heterozygotes. </p><p>Park et al. (2002) noted that an E326K substitution had been identified in patients with all 3 types of Gaucher disease, but in each instance it was found on the same allele with another GBA mutation (see, e.g., 606463.0011). The authors identified the E326K allele in 1.3% of patients with Gaucher disease and in 0.9% of controls, indicating that it is a polymorphism. Montfort et al. (2004) performed functional analyses of 13 GBA mutant alleles identified in Gaucher disease patients. The mutations were expressed in Sf9 cells using a baculovirus expression system. The authors obtained results suggesting that the E326K mutation should be considered a 'modifier variant' rather than a neutral polymorphism, as previously suggested (Grace et al., 1999; Park et al., 2002). </p><p>Tayebi et al. (2003) studied DNA samples from 240 patients with Gaucher disease, using several complementary approaches to identify and characterize recombinant alleles. Among 480 alleles studied, 59 recombinant alleles were identified, including 34 gene conversions, 18 fusions, and 7 downstream duplications. At least 1 recombinant allele was present in 22% of the patients. In patients with Gaucher disease types I, II, and III, the authors found recombinant alleles with the following frequencies among alleles: 26 of 310, 18 of 74, and 15 of 96, respectively. Several patients carried 2 recombinations or mutations on the same allele. Generally, alleles resulting from nonreciprocal recombination (gene conversion) could be distinguished from those arising by reciprocal recombination (crossover and exchange), and the length of the converted sequence was determined. Homozygosity for a recombinant allele was associated with early lethality. Ten different sites of crossover and a shared pentamer motif sequence (CACCA) that could be a hotspot for recombination were identified. </p><p>Emre et al. (2008) analyzed the GBA gene in 57 unrelated Turkish patients with Gaucher disease and identified 103 mutant alleles (90.3%) carrying 11 different mutations, 3 of which were novel. The most frequent mutations included L444P (42%), N370S (30%), D409H (4.3%), and R463C (3.5%). </p><p><strong><em>Late-Onset Parkinson Disease and Lewy Body Dementia</em></strong></p><p>
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Goker-Alpan et al. (2004) reported 10 unrelated families with Gaucher disease in which obligate or confirmed carriers of GBA mutations developed Parkinson disease (see PD, 168600). In the family of a proband with Gaucher disease type III, the proband's father, paternal grandfather, and paternal great-aunt developed parkinsonism, and all were found to carry the mutant GBA allele that was found in the proband; 2 asymptomatic family members did not have the allele. Nine of 40 additional families with Gaucher disease had similar findings, but there was no correlation with specific GBA mutations. Most of the patients with parkinsonism developed neurocognitive changes. Goker-Alpan et al. (2004) suggested that heterozygosity for mutations in the GBA gene may be a risk factor for the development of parkinsonism. </p><p>Aharon-Peretz et al. (2004) reported an association between Parkinson disease and mutations in the GBA gene in Ashkenazi Jews by screening for 6 GBA mutations most common among this population. One or 2 mutant GBA alleles were identified in 31 (31.3%) of 99 Ashkenazi patients with idiopathic PD: 28 were heterozygous and 3 were homozygous for one of these mutations. Among 74 Ashkenazi patients with Alzheimer disease (AD; 104300), 3 (4.1%) were carriers of Gaucher disease and among 1,543 controls, 95 (6.2%) were carriers of Gaucher disease. Patients with PD had significantly greater odds of being carriers of Gaucher disease than did patients with Alzheimer disease (OR = 10.8) or controls (OR = 7.0). Among PD patients, those who were carriers of Gaucher disease were younger than those who were not carriers (mean age at onset, 60.0 years vs 64.2 years, respectively). Aharon-Peretz et al. (2004) suggested that some GBA mutations are susceptibility factors for Parkinson disease. </p><p>Aharon-Peretz et al. (2005) observed no difference in overall clinical manifestations and age at disease onset between 40 Ashkenazi Jewish PD patients who carried GBA mutations and 108 Ashkenazi Jewish PD patients without GBA mutations. </p><p>Toft et al. (2006) did not find an association between PD and 2 common GBA mutations, L444P and N370S, among 311 Norwegian patients with Parkinson disease. Mutant GBA alleles were identified in 7 (2.3%) patients and 8 (1.7%) controls. </p><p>Goker-Alpan et al. (2006) identified heterozygous mutations in the GBA gene in 8 (23%) of 35 patients with dementia with Lewy bodies (DLB; 127750). Four of these individuals carried the N370S mutation. One of 28 patients with Parkinson disease also carried a heterozygous N370S mutation. The authors postulated that a mutant GBA enzyme may take on a different and unexpected role that may contribute to the development of synucleinopathies. </p><p>Tan et al. (2007) identified a heterozygous L444P mutation in 8 (2.4%) of 331 Chinese patients with typical Parkinson disease and none of 347 controls. The age at onset was lower and the percentage of women higher in patients with the L444P mutation compared to those without the mutation. Tan et al. (2007) noted that the findings were significant because Gaucher disease is extremely rare among the Chinese. </p><p>Gan-Or et al. (2008) found that 75 (17.9%) of 420 Ashkenazi Jewish patients with PD carried a GBA mutation, compared to 4.2% of elderly and 6.35% of young controls. The proportion of severe GBA mutation carriers among patients was 29% compared to 7% among young controls. Severe and mild GBA mutations increased the risk of developing PD by 13.6- and 2.2-fold, and were associated with decreased age at PD onset. Gan-Or et al. (2008) concluded that genetic variance in the GBA gene is a risk factor for PD. </p><p>Gutti et al. (2008) identified the L444P mutation in 4 (2.2%) of 184 Taiwanese patients with PD. Six other GBA variants were identified in 1 patient each, yielding a total of 7 different mutations in 10 patients (5.4%). Gutti et al. (2008) suggested that sequencing the entire GBA gene would reveal additional variant that may contribute to PD. </p><p>Mata et al. (2008) identified heterozygosity for either the L444P or N370S mutation in 21 (2.9%) of 721 PD patients, 2 (3.5%) of 57 DLB patients, and 2 (0.4%) of 554 control individuals, all of European origin. Mata et al. (2008) estimated that the population-attributable risk for GBA mutations in Lewy body disorders was only about 3% in patients of European ancestry. </p><p>Nichols et al. (2009) identified 9 different mutations in the GBA gene, including 5 previously reported variants, in 161 (12.2%) of 1,325 patients with Parkinson disease from 99 (17.5%) of 566 PD families, respectively. Statistical analysis indicated that presence of 1 of the 5 previously reported GBA mutation was associated with increased risk of PD as well as earlier age at disease onset compared to controls without a GBA mutation. </p><p>In a 16-center worldwide study comprising 5,691 PD patients (including 780 Ashkenazi Jewish patients) and 4,898 controls (387 Ashkenazis), Sidransky et al. (2009) demonstrated a strong association between GBA mutations and Parkinson disease. Direct sequencing for only the L444P or N370S mutations identified either mutation in 15% of Ashkenazi patients and 3% of Ashkenazi controls. Among non-Ashkenazi individuals, either mutation was found in 3% of patients and less than 1% of controls. However, full gene sequencing identified GBA mutations in 7% of non-Ashkenazi patients. The odds ratio for any GBA mutation in patients compared to controls was 5.43 across all centers. Compared to PD patients without GBA mutations, patients with GBA mutations presented earlier with the disease, were more likely to have affected relatives, and were more more likely to have atypical manifestations, including cognitive defects. Sidransky et al. (2009) concluded that while GBA mutations are not likely a mendelian cause of PD, they do represent a susceptibility factor for development of the disorder. </p><p>Neumann et al. (2009) identified 14 different heterozygous mutations in the GBA gene in 33 (4.18%) of 790 British patients with Parkinson disease and in 3 (1.17%) of 257 controls. Three novel mutations (see, e.g., D443N; 606463.0048) were identified, and the most common mutations were L444P (in 11 patients), N370S (in 8 patients), and R463C (in 3 patients). Four (12%) patients had a family history of the disorder, whereas 29 (88%) had sporadic disease. The mean age at onset was 52.7 years, and 12 (39%) patients had onset before age 50. Fifteen (48.39%) of the patients with GBA mutations developed cognitive decline, including visual hallucinations. The male-to-female ratio of GBA carriers within the PD group was 5:2, which was significantly higher than that of the whole study group. Most patients responded initially to L-DOPA treatment. Neuropathologic examination of 17 GBA mutation carriers showed typical PD changes, with widespread and abundant alpha-synuclein pathology, and most also had neocortical Lewy body pathology. The prevalence of GBA mutations in British patients with sporadic PD was 3.7%, indicating that mutations in the GBA gene may be the most common risk factor for development of PD in this population. In an accompanying letter, Gan-Or et al. (2009) found that the data presented by Neumann et al. (2009) indicated that patients with mild GBA mutations had later age at onset (62.9 years vs 49.8 years) and lower frequency of cognitive symptoms (25% vs 55.6%) compared to patients with severe GBA mutations. </p><p>PD brains are characterized by accumulation of aggregated alpha-synuclein (SNCA; 163890), in addition to neurodegeneration. Mazzulli et al. (2011) found that postmortem brains of patients with GD and features of PD, as well as mouse models of GD, showed neuronal accumulation of SNCA. Functional loss of GCase and resultant GlcCer accumulation in cultured mouse cortical neurons and human neurons reprogrammed from induced pluripotent stem cells resulted in compromised lysosomal degradation of long-lived proteins, including SNCA. Elevated cellular GlcCer also promoted SNCA aggregation. SNCA accumulation in turn inhibited normal lysosomal GCase activity in neurons and PD brain. In apparently normal human cortical samples, SNCA protein content, particularly high molecular mass species, correlated inversely with GCase activity. Mazzulli et al. (2011) hypothesized that a positive-feedback loop between defective SNCA and/or GCase could lead to self-propagating neurodegeneration over time. </p><p>Gonzalez-del Rincon et al. (2013) identified a heterozygous L444P mutation in 7 (5.5%) of 128 Mexican Mestizo patients with early-onset PD (before 45 years of age) and in none (0%) of 252 ethnically matched controls. Six (85.7%) of the 7 patients had psychiatric symptoms, including major depressive disorder, generalized anxiety disorder, and obsessive compulsive disorder, which was significantly higher than the prevalence of these disorders in controls (24.7%). In addition, 57% of mutation carriers presented with cognitive decline compared to 5.7% of controls. The N370S mutation was not found in any of the Mexican individuals, suggesting a similarity to Asian populations in which the N370S mutation is almost nonexistent. Gonzalez-del Rincon et al. (2013) concluded that the risk for PD conferred by GBA mutations may be higher than previously thought, and that GBA-associated PD may predispose to psychiatric symptoms. </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>Theophilus et al. (1989) confirmed the high frequency of the N370S mutation in Ashkenazi Jewish patients with type I Gaucher disease. Homozygotes were mildly affected older persons, and the mutant allele was not found in any patient with neuronopathic disease. Furthermore, they confirmed that the L444P mutation was the predominant allele in Gaucher disease type II and type III. </p><p>Koprivica et al. (2000) used several approaches, including direct sequencing, Southern blotting, long-template PCR, restriction digestions, and the amplification refraction mutation system, to genotype 128 patients with type I Gaucher disease (64 of Ashkenazi Jewish ancestry and 64 of non-Jewish extraction) and 24 patients with type III Gaucher disease. More than 97% of the mutant alleles were identified. Fourteen novel mutations and many rare mutations were detected. Recombinant alleles were found in 19% of the patients. Four mutations (N370S, 84insG, IVS2+1G-A, and L444P) accounted for 93% of the mutant alleles in the Ashkenazi Jewish type I patients, but for only 49% of mutant alleles in the non-Jewish type I patients. Heterozygosity for N370S resulted in type I Gaucher disease, whereas homozygosity for L444P was associated with type III. Genotype L444P/recombinant allele resulted in type II Gaucher disease, and homozygosity for a recombinant allele was associated with perinatal lethal disease. </p><p>Homozygosity for the D409H mutation (606464.0006) has been reported in Arab (Abrahamov et al., 1995) and British/German (Beutler et al., 1995) patients with neuronopathic Gaucher disease and cardiovascular calcifications, a specific subtype known as 'Gaucher disease type IIIC' (231005) (Bohlega et al., 2000). These reports demonstrate a particularly tight pan-ethnic association between phenotype and genotype in this variant form of Gaucher disease. </p><p>Ron and Horowitz (2005) tested glucocerebrosidase protein levels, N-glycans processing, and intracellular localization in skin fibroblasts derived from patients with Gaucher disease. Their results strongly suggested that mutant glucocerebrosidase variants presented variable levels of ER retention and underwent ER-associated degradation in the proteasomes. The degree of ER retention and proteasomal degradation was 1 of the factors that determined Gaucher disease severity. </p><p>In a review of the molecular genetics of Gaucher disease, Hruska et al. (2008) noted that most GBA mutations can be found in patients with various forms of the disorder. The phenotype is mainly determined by the combination of mutations on both alleles; thus the prediction of phenotype from genotypic data has limited utility. In addition, it has become increasingly difficult to categorize patients into 1 of the 3 classic types of Gaucher disease, indicating that the phenotypes fall into a continuum, with the major distinction being the presence and degree of neurologic function. </p>
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<p>Beutler (1993) stated that the 2 most common mutations in the Ashkenazi Jewish population were N370S and 84insG, representing approximately 77% and 13% of mutant alleles, respectively. These 2 mutations, together with L444P, IVS2+1G-A, and V394L (606463.0005), account for 98% of the disease-causing alleles in this population. Each of these mutations was found in the context of a single haplotype, consistent with a founder effect. </p><p>Diaz et al. (2000) used short tandem repeat (STR) markers to map a 9.3-cM region containing the GBA locus and to genotype 261 Ashkenazi Jewish N370S chromosomes, 60 European non-Jewish N370S chromosomes, and 62 Ashkenazi Jewish 84insG chromosomes. A highly conserved haplotype at 4 markers flanking GBA was observed on both the Ashkenazi chromosomes and the non-Jewish N370S chromosomes, suggesting the occurrence of a founder common to the 2 populations. The presence of different divergent haplotypes suggested the occurrence of de novo, recurrent N370S mutations. In contrast, a different conserved haplotype at these markers was identified on the 84insG chromosomes, which was unique to the Ashkenazi population. On the basis of linkage disequilibrium values, the non-Jewish European N370S chromosomes had greater haplotype diversity and less linkage disequilibrium at the markers flanking the conserved haplotype than did the Ashkenazi N370S chromosomes. This finding was considered consistent with the presence of the N370S mutation in the non-Jewish European population before the founding of the Ashkenazi population. Coalescence analyses for the N370S and 84GG mutations estimated similar coalescence times, of 48 and 55.5 generations ago, respectively. (Coalescence time refers to the number of generations to the most recent common ancestor, MRCA.) The results of these studies were consistent with a significant bottleneck occurring in the Ashkenazi population during the first millennium, when the population became established. </p>
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<strong>Animal Model</strong>
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<p>A naturally occurring canine model of Gaucher disease was reported by van de Water et al. (1979) but was not propagated. Tybulewicz et al. (1992) produced a murine model by targeted disruption of the mouse Gba gene. A null allele was created in embryonic stem cells, and the genetically modified cells were used to establish a mouse strain carrying the mutation. Mice homozygous for the mutation had less than 4% of normal glucocerebrosidase activity, died within 24 hours of birth, and stored glucocerebroside in lysosomes of cells of the reticuloendothelial system. </p><p>To produce mice with point mutations that correspond to the clinical types of Gaucher disease, Liu et al. (1998) devised a highly efficient 1-step mutagenesis method, called the single insertion mutagenesis procedure (SIMP), to introduce human disease mutations into the mouse Gba gene. By use of SIMP, they generated mice carrying either the very severe triply mutant allele (606463.0009) that can cause type II disease or the less severe L444P mutation associated with type III disease. Mice homozygous for the triple mutation had little GBA enzyme activity and accumulated glucosylceramide in brain and liver. In contrast, the mice homozygous for the L444P mutation had higher levels of GBA activity and no detectable accumulation of glucosylceramide in brain and liver. Surprisingly, both point mutation mice died within 48 hours of birth, apparently of a compromised epidermal permeability barrier caused by defective glucosylceramide metabolism in the epidermis. </p><p>Enquist et al. (2007) generated transgenic mice with targeted disruption of the Gba gene, but low expression of the gene in skin to prevent early lethality. The mice showed a phenotype similar to the severe neuronopathic form of Gaucher disease, including rapid motor dysfunction, seizures, and hyperextension of the neck associated with severe neurodegeneration and apoptotic neuronal cell death. Some neurons had large vacuoles indicating neuronal lipid accumulation. A second mouse model with Gba deficiency restricted to neural and glial cell progenitors demonstrated a similar neuropathology as the first mouse model, but with a delayed onset and slower disease progression. These findings indicated that Gba deficiency within microglial cells of hematopoietic origin is not the primary determinant of the CNS pathology, but may influence disease progression. The findings also showed that normal hematopoietic-derived microglial cells could not rescue the neurodegenerative phenotype. </p>
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<strong>ALLELIC VARIANTS</strong>
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<strong>48 Selected Examples):</strong>
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<strong>.0001 GAUCHER DISEASE, TYPE II</strong>
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GAUCHER DISEASE, TYPE III, INCLUDED<br />
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GAUCHER DISEASE, TYPE I, INCLUDED<br />
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PARKINSON DISEASE, LATE-ONSET, SUSCEPTIBILITY TO, INCLUDED<br />
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DEMENTIA, LEWY BODY, SUSCEPTIBILITY TO, INCLUDED
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GBA, LEU444PRO
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SNP: rs421016,
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gnomAD: rs421016,
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ClinVar: RCV000004509, RCV000004510, RCV000004511, RCV000004512, RCV000004513, RCV000004533, RCV000004534, RCV000004535, RCV000004536, RCV000020150, RCV000225393, RCV000225500, RCV000413257, RCV000626625, RCV001004112, RCV001197164, RCV001781179, RCV001836696, RCV002476924, RCV003398445, RCV003987311, RCV004018555
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<p>The leu444-to-pro (L444P) substitution in exon 10 of the GBA gene has been reported as resulting from a 1448T-C transition (Zimran et al., 1989) and from a 6433T-C transition (Latham et al., 1990), depending upon the reference sequence cited. This mutation has alternatively been referred to as LEU483PRO (Saranjam et al., 2013). </p><p>Reczek et al. (2007) stated that the L444P mutation results in retention of GBA in the ER. They found that overexpression of the human GBA receptor, LIMP2 (SCARB2; 602257), in mouse embryonic fibroblasts rescued lysosomal targeting of GBA with the L444P mutation. </p><p><strong><em>Gaucher Disease</em></strong></p><p>
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Tsuji et al. (1987) identified the L444P substitution in the GBA gene in patients with Gaucher disease types I (230800), II (230900), and III (231000). Two of the 5 patients with type II and 7 of the 11 with type III were homozygous for this mutation, whereas 4 of 20 patients with type I Gaucher disease had this mutant allele in heterozygous state. The mutant allele was not found in 29 normal controls. The L444P substitution occurs naturally in the GBA pseudogene. </p><p>Wigderson et al. (1989) identified the L444P mutation in patients with type I, type II, and type III disease. One patient with type II disease was compound heterozygous for L444P and P415R (606463.0002). Firon et al. (1990) found the L444P mutation in both Ashkenazi Jewish and non-Jewish patients with type I Gaucher disease, but only homozygotes with this mutation had the neurologic forms type II or III. </p><p>Dahl et al. (1990) found that the Norrbottnian form of Gaucher disease (type III) in Sweden is caused by the L444P mutation. </p><p>In 3 patients with type I and 1 patient with type II Gaucher disease, Hong et al. (1990) identified a complex allele with 3 point mutations in the GBA gene (606463.0009), 1 of which was L444P. </p><p>Koprivica et al. (2000) found that homozygosity for L444P was associated with type III Gaucher disease. </p><p>Saranjam et al. (2013) reported 2 unrelated infants with severe, lethal type II Gaucher disease who were compound heterozygous for 2 mutations in the GBA gene, one of which was L444P. While the other mutation was identified in the paternal line of each patient (see, e.g., T323I, 606463.0017), the L444P allele was not detected in DNA samples from either patient's mother, suggesting that it occurred either as a result of germline mosaicism or as a de novo mutation in 1 ovum that took place during cell division. The findings had implications for genetic counseling, in that even if only 1 parent is found to be a carrier for a recessive disorder, the chance of having an affected child may not be zero. Saranjam et al. (2013) noted that the L444P change occurs at a known mutational hotspot. </p><p><strong><em>Parkinson Disease</em></strong></p><p>
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Tan et al. (2007) identified a heterozygous L444P mutation in 8 (2.4%) of 331 Chinese patients with typical Parkinson disease (168600) and none of 347 controls. The age at onset was lower and the percentage of women higher in patients with the L444P mutation compared to those without the mutation. Tan et al. (2007) noted that the findings were significant because Gaucher disease is extremely rare among the Chinese. </p><p>Gutti et al. (2008) identified the L444P mutation in 4 (2.2%) of 184 Taiwanese patients with PD. Six other GBA variants were identified in 1 patient each, yielding a total of 7 different mutations in 10 patients (5.4%). Gutti et al. (2008) suggested that sequencing the entire GBA gene would reveal additional variant that may contribute to PD. </p><p>Neumann et al. (2009) identified a heterozygous L444P mutation in 11 (1.39%) of 790 British patients with PD, which was not found in 257 controls. </p><p>Gonzalez-del Rincon et al. (2013) identified a heterozygous L444P mutation in 7 (5.5%) of 128 Mexican Mestizo patients with early-onset PD (before 45 yeras of age) and in none (0%) of 252 ethnically matched controls. Six (85.7%) of the 7 patients had psychiatric symptoms, including major depressive disorder, generalized anxiety disorder, and obsessive compulsive disorder, which was significantly higher than the prevalence of these disorders in controls (24.7%). In addition, 57% of mutation carriers presented with cognitive decline compared to 5.7% of controls. Gonzalez-del Rincon et al. (2013) concluded that the risk for PD conferred by GBA mutations may be higher than previously thought, and that GBA-associated PD may predispose to psychiatric symptoms. </p><p><strong><em>Lewy Body Dementia</em></strong></p><p>
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Mata et al. (2008) identified heterozygosity for the L444P mutation in 10 (1.4%) of 721 PD patients, 1 (1.8%) of 57 patients with Lewy body dementia (DLB; 127750), and 0 of 554 control individuals, all of European origin. Mata et al. (2008) estimated that the population-attributable risk for GBA mutations in Lewy body disorders was only about 3% in patients of European ancestry. </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 GAUCHER DISEASE, TYPE II</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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GBA, PRO415ARG
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<br />
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SNP: rs121908295,
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ClinVar: RCV000004514
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with Gaucher disease type II (230900), Wigderson et al. (1989) identified compound heterozygosity for 2 mutations in the GBA gene: a 5976C-G transversion, resulting in a pro415-to-arg (P415R) substitution, and L444P (606463.0001). </p><p>Reczek et al. (2007) found that GBA with the P415R mutation was retained in the ER of transfected mouse embryonic fibroblasts. Overexpression of the GBA receptor, LIMP2 (SCARB2; 602257), did not rescue lysosomal targeting of GBA with the P415R mutation, suggesting that this mutation directly or indirectly interferes with interaction between GBA and LIMP2. </p>
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</span>
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</div>
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</div>
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</div>
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<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 GAUCHER DISEASE, TYPE I</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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PARKINSON DISEASE, LATE-ONSET SUSCEPTIBILITY TO, INCLUDED<br />
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DEMENTIA, LEWY BODY, SUSCEPTIBILITY TO, INCLUDED
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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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GBA, ASN370SER
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<br />
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SNP: rs76763715,
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gnomAD: rs76763715,
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ClinVar: RCV000004515, RCV000004516, RCV000004517, RCV000079336, RCV000396221, RCV000414782, RCV000515439, RCV001004117, RCV001195689, RCV001197918, RCV001270528, RCV002247244, RCV003982824, RCV004018556, RCV004555830
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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 />
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<p><strong><em>Gaucher Disease</em></strong></p><p>
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The asn370-to-ser (N370S) substitution in exon 9 of the GBA gene has been reported as resulting from a 5841A-G transition (Latham et al., 1990) and from a 1226A-G transition (Tsuji et al., 1988), depending upon the reference sequence cited. It is the most common Gaucher disease allele in the Ashkenazi Jewish population and is only associated with the nonneuronopathic type I form of Gaucher disease (230800) (Zimran et al., 1989). </p><p>Tsuji et al. (1988) identified the N370S substitution in an Ashkenazi Jewish patient with type I Gaucher disease. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation occurs exclusively with the type I phenotype. None of 6 type II (230900) patients, 11 type III (231000) patients, or 12 normal controls had this allele. In contrast, 15 of 24 type I patients had 1 allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazi Jewish type I patients had only 1 allele with this mutation, suggesting allelic heterogeneity even in this population. One patient with type I disease was compound heterozygous for N370S and L444P (606463.0001). </p><p>Zimran et al. (1989) found that the N370S substitution was associated with a mild clinical phenotype compared to L444P. Eight of 22 patients homozygous for N370S were entirely symptom-free. In symptomatic patients, the clinical features of the N370S homozygotes were usually related to splenomegaly and thrombocytopenia. </p><p>Kolodny et al. (1989, 1990) studied an unusual Ashkenazi Jewish family with affected members in 3 successive generations. Both N370S and L444P segregated in the family; 4 affected individuals were homozygous for N370S mutation, while 3 others were compound heterozygotes for the 2 mutations. Clinical severity was more marked in compound heterozygotes than in homozygotes. Firon et al. (1990) found the N370S mutation in type I patients only. </p><p>Zimran et al. (1990) identified a 3931G-A polymorphism in intron 6 of the GBA gene, termed PvuII. Analysis of 54 unrelated Jewish Gaucher patients showed strong linkage disequilibrium between the negative polymorphism genotype and the common Jewish N370S mutation. </p><p>Among 593 unrelated normal Ashkenazi Jewish individuals, Zimran et al. (1991) identified 37 heterozygotes and 2 homozygotes for the N370S mutation, yielding an allele frequency of 0.035. Among 1,528 Ashkenazi Jewish individuals, Beutler et al. (1993) identified 87 heterozygotes and 4 homozygotes for N370S, yielding a frequency of 0.0311; pooling with data reported by Zimran et al. (1991) yielded a frequency of 0.032 for the N370S allele. </p><p>Mistry et al. (1992) used the amplification refractory mutation system (ARMS) for direct detection of GBA mutations in Gaucher disease. PCR primers were designed to discriminate between mutant and wildtype alleles and to allow separation from products of the related pseudogene. The N370S mutation and a 2-bp insertion (84insGG; 606463.0014) were found exclusively in 5 patients of Ashkenazi Jewish descent. </p><p>Van Weely et al. (1993) studied the properties of control and N370S mutant GBA in vitro and in vivo. The results indicated that the intralysosomal pH in the intact cell has a critical influence on the activation state of N370S GBA and its ability to hydrolyze substrate. This phenomenon may partly explain the clinical heterogeneity in patients with Gaucher disease caused by the N370S mutation. </p><p>Walley et al. (1993) found that the N370S mutation accounted for 26% of Gaucher disease alleles among non-Jewish patients in the United Kingdom (total alleles = 54). They found a correlation between the presence of at least 1 N370S allele and mild disease. The L444P mutation accounted for 35% of the alleles and the remaining 39% were rare or undefined. </p><p>The N370S mutation and the 84insGG mutation reportedly account for approximately 70% and 10%, respectively, of mutations in the Jewish population. Ida et al. (1995) found neither mutation in 32 unrelated Japanese Gaucher patients, of whom 20 were type I, 6 were type II, and 6 were type III. </p><p>Cormand et al. (1998) found that N370S and L444P accounted for 66.1% of Gaucher disease alleles in Spain. Linkage disequilibrium was detected between these 2 mutations and an intragenic polymorphism, indicating that expansion of founder alleles occurred in both cases. Analysis of several microsatellite markers close to the GBA gene allowed them to establish a putative haplotype of the ancestral N370S chromosome. </p><p>Koprivica et al. (2000) found that homozygosity or heterozygosity for N370S resulted in type I Gaucher disease. </p><p>Dimitriou et al. (2010) determined that the frequency of the N370S allele is 0.0046 in the Greek population. </p><p><strong><em>Parkinson Disease and Lewy Body Dementia</em></strong></p><p>
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Mata et al. (2008) identified heterozygosity for the N370S mutation in 11 (1.5%) of 721 patients with Parkinson disease (PD; 168600), 1 (1.8%) of 57 patients with Lewy body dementia (DLB; 127750), and 2 (0.4%) of 554 control individuals. All individuals were of European origin. Mata et al. (2008) estimated that the population-attributable risk for GBA mutations in Lewy body disorders was only about 3% in patients of European ancestry. </p><p>Neumann et al. (2009) identified a heterozygous N370S mutation in 8 (1.01%) of 790 British patients with PD and in 1 (0.39%) of 257 controls. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 GAUCHER DISEASE, TYPE I</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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GAUCHER DISEASE, PERINATAL LETHAL, INCLUDED
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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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GBA, ARG119GLN
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<br />
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SNP: rs79653797,
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gnomAD: rs79653797,
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ClinVar: RCV000004518, RCV000004519, RCV000020154, RCV001250522, RCV001781178
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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>The arg119-to-gln (R119Q) substitution in the GBA gene has been reported to result from a 3060G-A transition (Graves et al., 1988) and a 476G-A transition (Felderhoff-Mueser et al., 2004), depending upon the reference sequence cited. This mutation has also been referred to as ARG120GLN by others (Latham et al., 1990; Felderhoff-Mueser et al., 2004). </p><p>Graves et al. (1988) identified a heterozygous R119Q substitution in the GBA gene in 2 Ashkenazi Jewish cousins with Gaucher disease type I (230800). </p><p>In a premature infant with the perinatal lethal form of Gaucher disease (608013), Felderhoff-Mueser et al. (2004) identified compound heterozygosity for the R120Q mutation and an IVS10-1G-A substitution (606463.0046) in the GBA gene. </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>.0005 GAUCHER DISEASE, TYPE III</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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GAUCHER DISEASE, TYPE I, INCLUDED
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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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GBA, VAL394LEU
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<br />
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SNP: rs80356769,
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gnomAD: rs80356769,
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ClinVar: RCV000004520, RCV000004521, RCV000020148, RCV000762854, RCV001004115, RCV001382044, RCV001836694
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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>Theophilus et al. (1989) and Latham et al. (1990) identified a heterozygous 5912G-T transversion in the GBA gene, resulting in a val394-to-leu (V394L) substitution, in an Ashkenazi Jewish/Irish patient with Gaucher disease type III (231000) and an Ashkenazi Jewish patient with Gaucher disease type I (230800). The patient with type III disease was compound heterozygous for the V394L substitution on 1 allele and a complex substitution (606463.0009) and D409H (606463.0006) on the other allele. He developed psychomotor retardation and myoclonic seizures by age 5 years and died at 6 years. The patient with type I disease was compound heterozygous for V394L and N370S (606463.0003). Latham et al. (1990) suggested that the N370S allele protected the type I patient from the development of neuronopathic disease. </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>.0006 GAUCHER DISEASE, TYPE IIIC</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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GAUCHER DISEASE, TYPE I, INCLUDED<br />
|
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GAUCHER DISEASE, TYPE II, INCLUDED<br />
|
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GAUCHER DISEASE, TYPE III, INCLUDED<br />
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GAUCHER DISEASE, PERINATAL LETHAL, INCLUDED
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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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GBA, ASP448HIS
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<br />
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SNP: rs1064651, rs77369218,
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gnomAD: rs1064651,
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ClinVar: RCV000004522, RCV000004523, RCV000004524, RCV000004525, RCV000004526, RCV000004580, RCV000004581, RCV000055773, RCV000079338, RCV000762853, RCV001004114, RCV001836695, RCV004018557
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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>Kurolap et al. (2019) noted that the ASP409HIS mutation is annotated as ASP448HIS (D448H), resulting from a c.1342G-C transversion (c.1342G-C, NM_000157.3) in the GBA gene. The sequence includes the 39-residue signal peptide. </p><p>The asp409-to-his (D409H) substitution in exon 9 of the GBA gene has also been reported as resulting from a c.957G-C transversion, based on a different reference sequence (Beutler, 1992). </p><p>Theophilus et al. (1989) identified a heterozygous D409H mutation in the GBA gene in 2 patients with type I Gaucher disease (230800) and 1 patient with type III (231000) Gaucher disease. </p><p>Cormand et al. (1995) identified heterozygosity for the D409H allele in Spanish patients with types I, II (230900), and III Gaucher disease. All patients had markedly different clinical phenotypes. Cormand et al. (1995) found that the D409H mutation accounted for 4 (5.7%) of 70 mutated alleles among 35 Spanish patients with Gaucher disease. </p><p>Chabas et al. (1995) described 3 Spanish sisters with an unusual form of Gaucher disease, later designated type IIIC (231005) (Bohlega et al., 2000), due to a homozygous D409H substitution in the GBA gene. Hepatosplenomegaly was present in all 3 sibs; characteristic Gaucher cells were found on bone marrow aspirate in 2 and in the splenectomy specimen in the third. The patients had cardiovascular abnormalities consisting of calcification of the ascending aorta and of the aortic and mitral valves. Neurologic findings included ophthalmoplegia and saccadic eye movements in 2 of the sisters, and tonic-clonic seizures in the third. The 3 sisters died at ages 16, 15, and 13, 2 of them having undergone aortic valve replacement. </p><p>Uyama et al. (1997) identified the homozygous D409H mutation in 3 Japanese adult sibs reported by Uyama et al. (1992) who had Gaucher disease associated with supranuclear ophthalmoplegia and cardiovascular calcifications. </p><p>Homozygosity for the D409H mutation has been reported in Arab (Abrahamov et al., 1995) and British/German (Beutler et al., 1995) patients with Gaucher disease and cardiovascular calcifications. These reports demonstrate a particularly tight pan-ethnic association between phenotype and genotype in this variant form of Gaucher syndrome. </p><p>Bohlega et al. (2000) described 4 Saudi Arabian sibs with the D409H mutation who had impaired horizontal saccades and aortic and mitral valve calcification without other systemic disease. Bohlega et al. (2000) suggested the designation 'Gaucher disease type IIIC.' </p><p>Inui et al. (2001) reported a patient who was compound heterozygous for the D409H allele and another unidentified mutation. He had hydrocephalus, corneal opacities, deformed toes, and cardiac features typical of patients who are homozygous for this allele. However, he also had fibrous thickening of the splenic and hepatic capsules and massive hepatosplenomegaly, features which differed from patients homozygous for the D409H allele. Enzyme replacement therapy was given for 4 years, resulting in an improvement of visceral and hematologic abnormalities but no neurologic improvement. </p><p>Mignot et al. (2003) identified the D409H mutation in compound heterozygosity with another mutation in a fetus with perinatal lethal Gaucher disease (608013). </p><p>Emre et al. (2008) identified homozygosity for the D409H mutation in 2 unrelated Turkish patients with Gaucher disease, who had cardiac valvular involvement and severe cardiac disease associated with hepatosplenomegaly. </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>.0007 GAUCHER DISEASE, TYPE III</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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GBA, ASP448VAL
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<br />
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SNP: rs77369218,
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ClinVar: RCV000004527, RCV000020149, RCV000411499
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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 Caucasian patient with type III Gaucher disease (231000), Theophilus et al. (1989) identified compound heterozygosity for 2 mutations in the GBA gene: a 5958A-T transversion in exon 9, resulting in an asp409-to-val (D409V) substitution, and L444P (606463.0001). </p><p>The ASP409VAL variant is annotated as ASP448VAL based on sequence NM_000157.3; see 606463.0006. The sequence includes the 39-residue signal peptide.</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>.0008 GAUCHER DISEASE, TYPE I</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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GAUCHER DISEASE, TYPE II, INCLUDED<br />
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GAUCHER DISEASE, TYPE III, INCLUDED<br />
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PARKINSON DISEASE, LATE-ONSET, SUSCEPTIBILITY TO, INCLUDED
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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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GBA, ARG463CYS
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<br />
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SNP: rs80356771,
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gnomAD: rs80356771,
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ClinVar: RCV000004528, RCV000004529, RCV000004530, RCV000004531, RCV000020151, RCV000079343, RCV000762852, RCV001004110, RCV004018558, RCV004751200
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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 />
|
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<p><strong><em>Gaucher Disease</em></strong></p><p>
|
|
In a non-Jewish patient with type I Gaucher disease (230800), Hong et al. (1990) identified a 1504C-T transition in exon 10 of the GBA gene, resulting in an arg463-to-cys (R463C) substitution. </p><p>By the amplification refractory mutation system, Mistry et al. (1992) identified the R463C mutation and the L444P mutation (606463.0001) in association with rapidly progressive disease and neurologic involvement in non-Jewish patients (see 230900). </p><p>Park et al. (2003) identified the R463C mutation in patients with type III Gaucher disease (231000). </p><p><strong><em>Parkinson Disease</em></strong></p><p>
|
|
Neumann et al. (2009) identified a heterozygous R463C mutation in 3 (0.38%) of 790 British patients with Parkinson disease (PD; 168600) that was not found in 257 controls, suggesting that heterozygosity for the mutation increases susceptibility for development of PD. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0009 GAUCHER DISEASE, TYPE I</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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GAUCHER DISEASE, TYPE II, INCLUDED<br />
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GAUCHER DISEASE, TYPE III, INCLUDED<br />
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GAUCHER DISEASE, PERINATAL LETHAL, INCLUDED
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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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GBA, LEU444PRO, ALA456PRO, AND VAL460VAL
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<br />
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SNP: rs1135675, rs368060, rs421016,
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gnomAD: rs1135675, rs368060, rs421016,
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ClinVar: RCV000004509, RCV000004510, RCV000004511, RCV000004512, RCV000004513, RCV000004533, RCV000004534, RCV000004535, RCV000004536, RCV000020150, RCV000079341, RCV000079342, RCV000225393, RCV000225500, RCV000413257, RCV000626625, RCV001004112, RCV001197164, RCV001781179, RCV001836696, RCV002476924, RCV003129772, RCV003221801, RCV003398445, RCV003987311, RCV004018555
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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 non-Jewish patients with Gaucher disease type I (230800) and 1 non-Jewish patient with type II disease (230900), Hong et al. (1990) found a mutant allele containing 3 single-base substitutions in exon 10 of the GBA gene, resulting in L444P (606463.0001), ala456-to-pro (A456P), and val460-to-val (V460V) substitutions. This mutant allele was referred to as 'pseudopattern' because it has sequence identical to a small region of exon 10 in the pseudogene (Horowitz et al., 1989). At least one of the patients was a compound heterozygote; the other allele was N370S (606463.0003). The authors suggested either gene conversion or recombination as a possible mechanism. </p><p>Latham et al. (1990) independently found these 3 mutations on 1 allele in patients with types I, II, and III (231000) Gaucher disease. None was homozygous for the complex allele: all patients had it in compound heterozygosity with another pathogenic GBA mutation. </p><p>Sidransky et al. (1996) described homozygosity for this complex triply mutant allele in 2 conceptuses from an Afghan family with perinatal lethal Gaucher disease (608013). The first infant had severe hydrops fetalis with bilateral hydrothorax and fetal hypokinesia with multiple joint contractures. Other features included hepatosplenomegaly, pulmonary hypoplasia, muscular atrophy, dysmorphic facies, and ichthyosis-like changes of the skin. The infant died less than an hour after delivery. In the next pregnancy a prenatal diagnosis of Gaucher disease was made by enzyme assay on cultured amniocytes obtained at week 15. Neither hydrops nor joint contractures were found in the fetus aborted at 23 weeks' gestation. The complex mutant allele is thought to have arisen by gene conversion or a recombination event with the neighboring pseudogene. The findings are comparable to those in the 'knockout' Gaucher mouse in which absence of enzyme is incompatible with long survival (Sidransky et al., 1992; Tybulewicz et al., 1992). A presumed homozygote for this complex allele, behaving as a perinatal lethal, was reported by Strasberg et al. (1994) in a fetus of Macedonian/Ashkenazi Jewish parentage. </p><p>Stone et al. (2000) reported a male infant born to consanguineous Lebanese parents who was homozygous for this recombinant allele. Ultrasound scanning demonstrated reduced fetal movement, neck hyperextension, and hepatomegaly. He was born at 34 weeks' gestation and died shortly thereafter. Autopsy findings included thick collodion-like skin, ectropia, joint contractures, hepatosplenomegaly, and facial dysmorphism. Gaucher cells were seen in many tissues. The diagnosis of Gaucher disease was confirmed enzymatically. </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>.0010 GAUCHER DISEASE, TYPE I</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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|
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GBA, PHE216TYR
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<br />
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|
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SNP: rs74500255,
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gnomAD: rs74500255,
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ClinVar: RCV000004537, RCV000498055, RCV001004127, RCV001248860, RCV001705580, RCV002476925
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|
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</span>
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</div>
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-year-old, non-Jewish Caucasian girl with type I Gaucher disease (230800), Beutler and Gelbart (1990) identified a 764T-A transversion in the GBA gene, resulting in a phe216-to-tyr (F216Y) substitution. The patient was heterozygous for this mutation, which came from the father; the presumed abnormality in the other allele was not identified. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
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<span class="mim-text-font">
|
|
|
|
GBA, ASP140HIS AND GLU326LYS
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<br />
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|
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SNP: rs147138516, rs2230288,
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|
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gnomAD: rs147138516, rs2230288,
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|
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ClinVar: RCV000004538, RCV000252989, RCV000414984, RCV000415149, RCV000415387, RCV000487503, RCV000487788, RCV000586576, RCV001248923, RCV001509572, RCV001836745, RCV002468938, RCV004594032
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with type I Gaucher disease (230800), Eyal et al. (1991) identified 3 point mutations in the GBA gene. One chromosome, inherited from the mother, had a 3119G-A transition resulting in an asp140-to-his (D140H) substitution, and a 5309G-A transition resulting in a glu326-to-lys (E326K) substitution. The other chromosome, inherited from the father, had a 3170A-C transversion resulting in a lys157-to-gln (K157Q; 606463.0012) substitution. All 3 mutations were inherited through 3 generations; the his140 and lys326 mutations were transmitted together. Although 1 brother had neurologic features, postmortem analysis did not detect Gaucher cells in the central nervous system, and Eyal et al. (1991) concluded that he had an additional separate neurologic disorder. The other brother had clinical features consistent with type I Gaucher disease. </p><p>By functional analysis studies of mutant GBA proteins, Montfort et al. (2004) obtained results suggesting that the E326K substitution alone could be considered a 'modifier variant' rather than a neutral polymorphism, as previously suggested (Grace et al., 1999; Park et al., 2002). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 GAUCHER DISEASE, TYPE I</strong>
|
|
</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">
|
|
|
|
GBA, LYS157GLN
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|
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<br />
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|
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SNP: rs121908297,
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|
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ClinVar: RCV000004539, RCV001572837
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|
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</span>
|
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</div>
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 3170A-C transversion in the GBA gene, resulting in a lys157-to-gln (K157Q) substitution, that was found in compound heterozygous state in 2 brothers with type I Gaucher disease (230800) by Eyal et al. (1991), see 606463.0011. </p>
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|
</span>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 GAUCHER DISEASE, TYPE III</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
GAUCHER DISEASE, TYPE II, INCLUDED<br />
|
|
GAUCHER DISEASE, TYPE I, INCLUDED
|
|
</span>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
|
GBA, PHE213ILE
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|
<br />
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|
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SNP: rs381737,
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|
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gnomAD: rs381737,
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|
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ClinVar: RCV000004540, RCV000004541, RCV000004542, RCV000020158, RCV000790654, RCV002482827, RCV004018559, RCV004820816
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|
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with type III Gaucher disease (231000), Kawame and Eto (1991) identified a heterozygous 3548T-A transition in exon 6 of the GBA gene, resulting in a phe213-to-ile (F213I) substitution. Two additional unrelated Japanese patients with type II Gaucher disease (230900) were also found to carry this mutation. F231I is normally found in the GBA pseudogene. The patients were compound heterozygous for F213I and L444P (606463.0001). In a patient with type I Gaucher disease (230800), He et al. (1992) found compound heterozygosity for 2 mutations in the GBA gene: P213I and P289L (606463.0016). </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, 1-BP INS, 84G
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|
|
|
<br />
|
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|
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SNP: rs387906315,
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|
|
gnomAD: rs387906315,
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|
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|
|
ClinVar: RCV000004543, RCV000587723, RCV000790704, RCV001004138, RCV002476926, RCV004751201
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Ashkenazi Jewish patients with type I Gaucher disease (230800), Beutler et al. (1991) identified a 1-bp insertion (84insG) of a second guanine at cDNA nucleotide 84; the mutation was referred to as the '84GG' mutation. </p><p>Beutler et al. (1993) found that 10 of 2,305 normal Ashkenazi Jewish individuals were heterozygous for the 84GG insertion mutation, yielding an allele frequency of 0.00217. </p><p>Ida et al. (1995) did not identify the 84GG mutation in 32 unrelated Japanese Gaucher patients, of whom 20 were type I, 6 were type II (230900), and 6 were type III (231000). </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
GAUCHER DISEASE, TYPE II, INCLUDED
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, IVS2DS, G-A, +1
|
|
|
|
|
|
<br />
|
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|
|
SNP: rs104886460,
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|
|
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gnomAD: rs104886460,
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|
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ClinVar: RCV000004546, RCV000032094, RCV000177098, RCV000762856, RCV000790724, RCV001004137, RCV001253701, RCV004019534
|
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|
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</span>
|
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</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a survey of 100 unrelated Jewish patients with type I Gaucher disease (230800), Beutler et al. (1992) found that 5 of the mutant GBA alleles resulted from a splice site mutation in intron 2 (IVS2DS+1G-A), resulting in skipping of exon 2. The phenotype was associated with earlier onset and more severe disease compared to the common N370S mutation (606463.0003). </p><p>He and Grabowski (1992) identified the IVS2DS+1G-A transition in a moderately affected 9-year-old Ashkenazi Jewish patient with type I Gaucher disease. The transition was found also at the corresponding exon/intron boundary of the highly homologous pseudogene. This splicing mutation accounted for about 3.4% of the Gaucher disease alleles in the Ashkenazi Jewish population. </p><p>Stone et al. (2000) identified compound heterozygosity for the IVS2DS+1G-A mutation and L444P (606463.0001) in 2 unrelated patients with type II Gaucher disease (230900). </p>
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|
</span>
|
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</div>
|
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|
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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>.0016 GAUCHER DISEASE, TYPE I</strong>
|
|
</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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|
|
GBA, PRO289LEU
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<br />
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|
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SNP: rs121908298,
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|
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ClinVar: RCV000004547
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|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type I Gaucher disease (230800), He et al. (1992) found compound heterozygosity for 2 mutations in the GBA gene: a pro289-to-leu (P289L) and P213I (606463.0013) substitution. The latter mutation had previously been found in type III patients. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
GAUCHER DISEASE, TYPE II, INCLUDED
|
|
</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
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|
|
GBA, THR323ILE
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<br />
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SNP: rs76539814,
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gnomAD: rs76539814,
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ClinVar: RCV000004548, RCV000041967, RCV001193934, RCV002496255, RCV003137492
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type I Gaucher disease (230800), He et al. (1992) found compound heterozygosity for a thr323-to-ile (T323I) substitution and the R463C (606463.0008) mutation in the GBA gene. </p><p>In an infant with severe, lethal type II Gaucher disease (230900) and severely decreased glucocerebrosidase activity, Saranjam et al. (2013) identified compound heterozygosity for 2 mutations in the GBA gene: a c.1085C-T transition, resulting in a thr323-to-ile (T323I) substitution inherited from the unaffected father, and the common L444P mutation (606463.0001). However, the L444P mutation was not identified in several tissues from the mother, and her glucocerebrosidase activity was normal. The findings suggested that the L444P mutation occurred either as a result of germline mosaicism or as a de novo mutation in 1 ovum that took place during cell division. The findings had implications for genetic counseling, in that even if only 1 parent is found to be a carrier for a recessive disorder, the chance of having an affected child may not be zero. Saranjam et al. (2013) noted that the L444P change occurs at a known mutational hotspot. </p><p>Saranjam et al. (2013) alternatively referred to this mutation as THR362ILE. </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>.0018 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, 1-BP DEL, 72C
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<br />
|
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|
|
SNP: rs397518433,
|
|
|
|
|
|
|
|
ClinVar: RCV000004549
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old non-Jewish European patient with Gaucher disease type I (230800), Beutler et al. (1993) identified a 1-bp deletion (72delC; 1023delC in the genomic sequence) in the GBA gene. The nature of the other mutation was not determined. There were no neurologic findings. The mutation was suspected on the basis of SSCP analysis and confirmed by sequencing and by restriction endonuclease analysis. In this and the other 5 patients with 'new' mutations whom they described, Beutler et al. (1993) cited a severity score which varied in the group of patients from 2 to 15; the patient with the 1023delC mutation had a severity score of 5. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, PRO122SER
|
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|
<br />
|
|
|
|
SNP: rs121908299,
|
|
|
|
|
|
|
|
ClinVar: RCV000004550
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Beutler et al. (1993) identified homozygosity for a pro122-to-ser (P122S) mutation in a 3-year-old Native American patient with Gaucher disease type I (230800) of severity score 12 and no neurologic findings. The amino acid substitution was due to a 3065C-T transition (genomic DNA sequence) and abolished a KpnI restriction site. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, TYR212HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908300,
|
|
|
|
|
|
gnomAD: rs121908300,
|
|
|
|
|
|
ClinVar: RCV000004551, RCV001248859, RCV003133115
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Jewish patient with type I Gaucher disease (230800), Beutler et al. (1993) identified compound heterozygosity for 2 mutations in the GBA gene: a 751T-C transition (3545T-C in the genomic DNA), resulting in a tyr212-to-his (Y212H) substitution, and N370S (606463.0003). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, GLY478SER
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs121908301,
|
|
|
|
|
|
|
|
ClinVar: RCV000004552, RCV001171764, RCV004689409
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a non-Jewish European patient with type I Gaucher disease (230800), Beutler et al. (1993) identified compound heterozygosity for 2 mutations in the GBA gene: a 1549G-A transition (6628G-A in the genomic DNA) resulting in a gly478-to-ser (G478S) substitution, and N370S (606463.0003). The severity score was given as 15, the highest value in this particular series of reported cases. There were no neurologic symptoms. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, ARG496HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs75822236,
|
|
|
|
|
|
gnomAD: rs75822236,
|
|
|
|
|
|
ClinVar: RCV000004553, RCV000020153, RCV000762851, RCV000790684, RCV001004108, RCV001836698, RCV004018560
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 unrelated patients, 3 Jewish and 1 non-Jewish European, with type I Gaucher disease (230800), Beutler et al. (1993) identified a heterozygous 1604G-A transition (6683 in the genomic DNA sequence) in the GBA gene, resulting in an arg496-to-his (R496H) substitution. Age at diagnosis varied from 16 to 27 years. None had neurologic findings. Severity score varied from 2 to 9. The other mutation in 3 of the patients was that referred to as 84GG (606463.0014); the fourth patient, Jewish, had the common N370S mutation (606463.0003). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
GAUCHER DISEASE, PERINATAL LETHAL, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, 55-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356768,
|
|
|
|
|
|
|
|
ClinVar: RCV000004555, RCV000020147, RCV000173718, RCV000723462, RCV002500459
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a non-Jewish European patient with type I Gaucher disease (230800), Beutler et al. (1993) identified a 55-bp deletion (nucleotides 1263-1317 in the cDNA; nucleotides 5879-5933 in genomic DNA) in the GBA gene. The mutation was in compound heterozygous combination with the N370S mutation (606463.0003). The severity score was given as 12. </p><p>Stone et al. (2000) reported a preterm female infant, born to nonconsanguineous Australian parents, with collodion skin, ectropia, hepatosplenomegaly, and thrombocytopenia (608013). She had a leucocyte glucocerebrosidase activity of 53 pmol/min/mg (normal, 600-3200). She was compound heterozygous for the 55-bp deletion and an R257E substitution (606463.0041). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, VAL15LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908302,
|
|
|
|
|
|
|
|
ClinVar: RCV000004556
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By sequencing RT-PCR cDNAs from 5 unrelated Korean and 2 Taiwanese sibs with Gaucher disease type I (230800), Kim et al. (1996) identified 3 mutations in the GBA gene: V15L, G46E (606463.0025), and N188S (606463.0026). Each mutation resulted in a dysfunctional acid beta-glucosidase. The N188S allele was present in both the Korean and the Chinese populations, suggesting an ancient mutation. The G46E mutation was present in 2 unrelated Korean patients. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, GLY46GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs77829017,
|
|
|
|
|
|
gnomAD: rs77829017,
|
|
|
|
|
|
ClinVar: RCV000004532, RCV000781409, RCV004589496
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Kim et al. (1996) identified a gly46-to-glu (G46E) substitution in the GBA gene in 2 unrelated Korean patients with type I Gaucher disease (230800). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
GAUCHER DISEASE, TYPE III, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, ASN188SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs364897,
|
|
|
|
|
|
gnomAD: rs364897,
|
|
|
|
|
|
ClinVar: RCV000004557, RCV000004558, RCV000020156, RCV000723402, RCV001004131, RCV002504742, RCV005089160
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Kim et al. (1996) identified an asn188-to-ser (N188S) substitution in the GBA gene in both Korean and Chinese (Taiwanese) patients with type I Gaucher disease (230800), suggesting that this is an ancient mutation. </p><p>Park et al. (2003) identified a heterozygous N188S mutation in 4 unrelated adult patients with type III Gaucher disease and myoclonic epilepsy (231000). All were compound heterozygous for another pathogenic GBA mutation. </p><p>Montfort et al. (2004) demonstrated that the N188S mutant enzyme retains a relatively high level of activity, suggesting that it is probably a very mild mutation or a modifier variant. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, PHE216VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908303,
|
|
|
|
|
|
|
|
ClinVar: RCV000004559
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Gaucher disease type I (230800), Horowitz and Zimran (1994) reported a 4113T-A transversion of the GBA gene leading to a change from phenylalanine to valine at position 216. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, ALA309VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs78396650,
|
|
|
|
|
|
gnomAD: rs78396650,
|
|
|
|
|
|
ClinVar: RCV000004560
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type I Gaucher disease (230800), Latham et al. (1991) identified a 5259G-T transversion in the GBA gene, resulting in an ala309-to-val (A309V) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, TRP312CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908304,
|
|
|
|
|
|
|
|
ClinVar: RCV000004561
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type I Gaucher disease (230800), Latham et al. (1991) identified a 5269G-T transversion in the GBA gene, resulting in a trp312-to-cys (W312C) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 GAUCHER DISEASE, TYPE II</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, GLY325ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908305,
|
|
|
|
|
|
gnomAD: rs121908305,
|
|
|
|
|
|
ClinVar: RCV000004562, RCV000180535, RCV001197976, RCV001248922, RCV002504743
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type II Gaucher disease (230900), Eyal et al. (1990) identified compound heterozygosity for 2 mutations in the GBA gene: a 5306G-A transition, resulting in a gly325-to-arg (G325R) substitution, and C342G (606463.0031). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 GAUCHER DISEASE, TYPE II</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, CYS342GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908306,
|
|
|
|
|
|
|
|
ClinVar: RCV000004563
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type II Gaucher disease (230900), Eyal et al. (1990) identified compound heterozygosity for 2 mutations in the GBA gene: a 5357T-G transversion, resulting in a cys342-to-gly (C342G) substitution, and G325R (606463.0030). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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GBA, SER364THR
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<br />
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SNP: rs121908307,
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gnomAD: rs121908307,
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ClinVar: RCV000004564, RCV002281038
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a patient with type I Gaucher disease (230800), Latham et al. (1991) identified a 5424G-C transversion in the GBA gene, resulting in a ser364-to-thr (S364T) substitution. </p>
|
|
</span>
|
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</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>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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GBA, 259C-T
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<br />
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SNP: rs1141814,
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gnomAD: rs1141814,
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ClinVar: RCV000004565, RCV000589792, RCV001507457, RCV002247245, RCV002251874, RCV002476927, RCV004760320
|
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|
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|
|
</span>
|
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a Bedouin patient with type I Gaucher disease (230800), Rockah et al. (1997) identified a homozygous 259C-T transition (1763 genomic DNA) in the GBA gene. The patient was 26 years old and had moderate thrombocytopenia and an enlarged spleen and liver, as well as Gaucher cells in a bone marrow biopsy and low levels of glucocerebrosidase activity. The same mutation in compound heterozygous state had been described by Beutler et al. (1995) in a Bedouin patient with type I Gaucher disease; this patient carried a 1448G mutation in addition to the 259T mutation. His phenotype was severe but with no neurologic signs. </p>
|
|
</span>
|
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</div>
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<div>
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|
<br />
|
|
</div>
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|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 GAUCHER DISEASE, PERINATAL LETHAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
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|
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|
GBA, 1-BP DEL, CODON 139C
|
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|
<br />
|
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|
|
SNP: rs397518434,
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|
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|
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|
|
ClinVar: RCV000004566, RCV001580445
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a fetus with perinatal lethal Gaucher disease (608013), Tayebi et al. (1997) identified a homozygous 1-bp deletion in the GBA gene, resulting in a frameshift and premature termination of the protein in exon 6. This 22-week-old fetus, the offspring of a first-cousin marriage, had hydrops, external abnormalities, hepatosplenomegaly, and Gaucher cells in several organs. Western blot analysis confirmed absence of glucocerebrosidase protein. </p>
|
|
</span>
|
|
</div>
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|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 GAUCHER DISEASE, TYPE III</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
|
<div>
|
|
<span class="mim-text-font">
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|
|
|
GBA, ARG353GLY
|
|
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|
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|
<br />
|
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|
|
SNP: rs121908308,
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|
|
gnomAD: rs121908308,
|
|
|
|
|
|
ClinVar: RCV000004567
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs with Gaucher disease with neurologic involvement (231000), born of parents related as first cousins once removed, Parenti et al. (1998) identified a 5390C-G transversion in the GBA gene, resulting in an arg353-to-gly (R353G) substitution. The 3 affected sibs were all adults, the youngest being 26 years old. Neurologic signs observed in type III Gaucher disease, such as deficits of the saccadic eye movements, cerebellar abnormalities, or myoclonus, were not present in these 3 sisters. However, the oldest sister had generalized tonic-clonic seizures beginning at the age of 23 years, requiring therapy. The next younger sister with Gaucher disease had partial seizures, and the youngest sister with Gaucher disease had EEG and other electrophysiologic abnormalities indicative of dysfunction of the motor cortex. Since none of these clinical or laboratory findings were present in the sibs without Gaucher disease, Parenti et al. (1998) concluded that the GBA mutation was responsible for the neurologic involvement. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, PRO401LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs74598136,
|
|
|
|
|
|
|
|
ClinVar: RCV000004568
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Extensive lytic lesions in the mandible of a 19-year-old Ashkenazi Jewish woman led Wasserstein et al. (1999) to the diagnosis of type I Gaucher disease (230800). The patient had extensive skeletal involvement, marked hepatosplenomegaly, and deficient acid beta-glucosidase activity. Mutation analysis showed compound heterozygosity for 2 mutations in the GBA gene: an N370S mutation (606463.0003) and a pro401-to-leu (P401L) substitution in exon 9. Expression of the P401L allele resulted in an enzyme with a reduced catalytic activity, which was similar to that of the mild N370S mutant enzyme. The expression studies predicted a mild phenotype for the proposita's N370S/P401L genotype, which was inconsistent with her severe diffuse skeletal disease and organ involvement. Since lytic mandibular lesions may be complicated by osteomyelitis, pathologic fractures, and tooth loss, Wasserstein et al. (1999) suggested that regular dental assessments in type I Gaucher disease are warranted. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 GAUCHER DISEASE, PERINATAL LETHAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, HIS311ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs78198234,
|
|
|
|
|
|
gnomAD: rs78198234,
|
|
|
|
|
|
ClinVar: RCV000004569, RCV001781180
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 female sibs with perinatal lethal Gaucher disease (608013), Stone et al. (1999) identified a homozygous mutation in exon 8 of the GBA gene, resulting in a his311-to-arg (H311R) substitution. The older sib was hydropic and delivered dead at 31 weeks' gestation. The second infant was hydropic and delivered alive at 30 weeks' gestation but died shortly after birth. The parents were a consanguineous couple from Cape Verde. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 GAUCHER DISEASE, PERINATAL LETHAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, ARG359TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908309,
|
|
|
|
|
|
gnomAD: rs121908309,
|
|
|
|
|
|
ClinVar: RCV000004570, RCV000585360, RCV000780288, RCV001249081, RCV002490309
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male infant with perinatal lethal Gaucher disease (608013), Stone et al. (1999) identified compound heterozygosity for 2 mutations in the GBA gene: a mutation in exon 8 resulting in an arg359-to-ter (R359X) substitution, and a mutation in exon 9 resulting in a val398-to-phe (V398F) substitution (606463.0039). The patient's father was from Surinam and his mother was Dutch. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 GAUCHER DISEASE, PERINATAL LETHAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, VAL398PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908310,
|
|
|
|
|
|
gnomAD: rs121908310,
|
|
|
|
|
|
ClinVar: RCV000004544
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the mutation in exon 9 of the GBA gene, resulting in a val398-to-phe (V398F) substitution, that was found in compound heterozygous state in a male infant with perinatal lethal Gaucher disease (608013) by Stone et al. (1999), see 606463.0038. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
GAUCHER DISEASE, TYPE III, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, GLY377SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908311,
|
|
|
|
|
|
gnomAD: rs121908311,
|
|
|
|
|
|
ClinVar: RCV000004571, RCV000004572, RCV000055772, RCV000723428, RCV001004116, RCV001270486, RCV002482828
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Portuguese patients with type I Gaucher disease (230800), Amaral et al. (1999) identified homozygosity for a gly377-to-ser (G377S) substitution in the GBA gene. All 3 had mild to moderate severity with severity score indices (SSI), as defined by Zimran et al. (1989), of 8, 14, and 10, respectively. One of them had had splenectomy at age 9; the other 2 had recognized onset at ages 39 and 48 years. G377S seems to be common in Iberian patients, representing 7% and 5% of alleles in Portuguese and Spanish patients, respectively, according to Amaral et al. (1999). </p><p>Park et al. (2003) identified a heterozygous G377S mutation in patients with type III Gaucher disease (231000); they had additional pathogenic GBA mutations. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0041 GAUCHER DISEASE, PERINATAL LETHAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, ARG257GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs78973108,
|
|
|
|
|
|
gnomAD: rs78973108,
|
|
|
|
|
|
ClinVar: RCV000004573, RCV000020159, RCV000079357, RCV000762855, RCV001004125, RCV001836699, RCV003225017, RCV004554584
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg257-to-glu (R257E) mutation in the GBA gene that was found in compound heterozygous state in a preterm infant with perinatal lethal Gaucher disease (608013) by Stone et al. (2000), see 606463.0023. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0042 GAUCHER DISEASE, PERINATAL LETHAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, ARG131LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356763,
|
|
|
|
|
|
gnomAD: rs80356763,
|
|
|
|
|
|
ClinVar: RCV000004574, RCV000020155
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sib pair with perinatal lethal Gaucher disease (608013), born to Mexican parents, Stone et al. (2000) detected homozygosity for a mutation in the GBA gene resulting in an arg131-to-leu (R131L) substitution. The parents were unaware of any common ancestry, and genetic studies to confirm or refute consanguinity were not possible. The first-born was a male infant with collodion skin at birth which improved within 2 weeks. He subsequently developed rapidly progressive neurologic disease and died at 7 months. Fibroblast glucocerebrosidase activity was 3% of control values. His sister was diagnosed by prenatal enzyme assay and was born at 37 weeks' gestation with collodion skin and hepatosplenomegaly. Her skin condition resolved during the first month of life, but she developed neurologic abnormalities and died at age 9 months. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0043 GAUCHER DISEASE, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
GAUCHER DISEASE, TYPE III, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, LYS79ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908312,
|
|
|
|
|
|
|
|
ClinVar: RCV000004575, RCV000004576, RCV000790694, RCV002281694
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Zhao et al. (2003) described a 57-year-old woman of Cherokee ancestry with Gaucher disease type I (230800) who was homozygous for a 2855G-C transversion in exon 4 of the GBA gene causing a lys79-to-asn (K79N) substitution. They also described a 2-year-old male of Caucasian/Cherokee ancestry with Gaucher disease type III (231000) who was a compound heterozygote for the same K79N allele and a novel complex mutation (null allele). The K79N allele was identical in the 2 cases as determined by complete gene sequencing, suggesting a founder effect. The discrepant phenotypes (Gaucher disease types I and III) in these 2 patients provided support for a threshold of residual activity necessary to 'protect' the CNS from the pathogenic effects of the disease. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0044 GAUCHER DISEASE, PERINATAL LETHAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GBA, PHE251LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908313,
|
|
|
|
|
|
|
|
ClinVar: RCV000004577
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant with the perinatal lethal variant of Gaucher disease (608013), Zhao et al. (2003) described compound heterozygosity for 2 mutations in the GBA gene: IVS2+1G-A (606463.0015) and a 5101C-A transversion resulting in a phe251-to-leu (F251L) substitution. Both enzyme activity and protein were greatly decreased in cultured skin fibroblasts. After birth, the patient was noted to have absent respiratory effort, tight shiny skin, a heart murmur, and frequent myoclonic jerks and died at age 1 month due to respiratory failure. </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>.0045 GAUCHER DISEASE, TYPE I</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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GBA, LEU371VAL
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<br />
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SNP: rs121908314,
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ClinVar: RCV000004578
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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 6 affected members in 3 generations of a consanguineous Lebanese family with moderately severe type I Gaucher disease (230800), Shamseddine et al. (2004) identified homozygosity for a 1228C-G transversion in the GBA gene, resulting in a leu371-to-val (L371V) mutation. The disorder was more severe than that observed with the common N370S (606463.0003) mutation associated with type I Gaucher disease. </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>.0046 GAUCHER DISEASE, PERINATAL LETHAL</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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GBA, IVS10DS, G-A, -1
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<br />
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SNP: rs1571964338,
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ClinVar: RCV000004579
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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 premature infant with perinatal lethal Gaucher disease (608013), Felderhoff-Mueser et al. (2004) identified compound heterozygosity for the R120Q mutation (606463.0004) and a G-to-A substitution at the first position in the splice site of intron 10 of the GBA gene, resulting in the insertion of the first 11 basepairs of IVS10 and deletion of the first 11 basepairs of exon 11. </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>.0047 GAUCHER DISEASE, TYPE II</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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|
GAUCHER DISEASE, TYPE III, INCLUDED
|
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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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GBA, HIS255GLN AND ASP409HIS
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<br />
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SNP: rs1064651, rs367968666,
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gnomAD: rs1064651, rs367968666,
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ClinVar: RCV000004522, RCV000004523, RCV000004524, RCV000004525, RCV000004526, RCV000004580, RCV000004581, RCV000055773, RCV000079338, RCV000589369, RCV000762853, RCV001004114, RCV001004126, RCV001195955, RCV001248861, RCV001329068, RCV001836695, RCV002247685, RCV004018557, RCV004751398
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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 25-month-old girl with an atypical form of neuronopathic Gaucher disease between type II (230900) and type III (231000), Filocamo et al. (2005) identified homozygosity for a complex allele containing 2 GBA mutations in cis: an 882T-G transversion in exon 7 resulting in a his255-to-gln (H255Q) substitution and a 1342G-C transversion in exon 10 resulting in an asp409-to-his (D409H; 606463.0006) substitution. Onset of symptoms occurred at age 5 months with hepatosplenomegaly. A few months later, she developed neurologic features, including spasticity with persistent retroflexion of the neck, convergent strabismus, oculomotor apraxia, and abnormal MRI changes. At age 25 months, she showed slow symptom progression and was able to sit alone, walk with support, and pronounce some words. </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>.0048 PARKINSON DISEASE, LATE-ONSET, SUSCEPTIBILITY TO</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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GBA, ASP443ASN
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<br />
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SNP: rs75671029,
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gnomAD: rs75671029,
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|
|
ClinVar: RCV000004582, RCV001174737, RCV001582465, RCV001826414, RCV002490310
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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 1 (0.13%) of 790 British patients with Parkinson disease (PD; 168600), Neumann et al. (2009) identified a heterozygous 1444G-A transition in exon 10 of the GBA gene, resulting in an asp443-to-asn (D443N) substitution. The mutation was not found in 257 controls. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Dinur et al. (1986); Grabowski et al. (1985); Graves et al. (1986)
|
|
</span>
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<div>
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<br />
|
|
</div>
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
|
Abrahamov, A., Elstein, D., Gross-Tsur, V., Farber, B., Glaser, Y., Hadas-Halpern, I., Ronen, S., Tafakjdi, M., Horowitz, M., Zimram, A.
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|
<strong>Gaucher's disease variant characterized by progressive calcification of heart valves and unique genotype.</strong>
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Lancet 346: 1000-1003, 1995.
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[PubMed: 7475546]
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[Full Text: https://doi.org/10.1016/s0140-6736(95)91688-1]
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</p>
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<p class="mim-text-font">
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Aharon-Peretz, J., Badarny, S., Rosenbaum, H., Gershoni-Baruch, R.
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<strong>Mutations in the glucocerebrosidase gene and Parkinson disease: phenotype-genotype correlation.</strong>
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Neurology 65: 1460-1461, 2005.
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[PubMed: 16148263]
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[Full Text: https://doi.org/10.1212/01.wnl.0000176987.47875.28]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Aharon-Peretz, J., Rosenbaum, H., Gershoni-Baruch, R.
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<strong>Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews.</strong>
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New Eng. J. Med. 351: 1972-1977, 2004.
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[PubMed: 15525722]
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[Full Text: https://doi.org/10.1056/NEJMoa033277]
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</p>
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<li>
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<p class="mim-text-font">
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Amaral, O., Lacerda, L., Marcao, A., Pinto, E., Tamagnini, G., Sa Miranda, M. C.
|
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<strong>Homozygosity for two mild glucocerebrosidase mutations of probable Iberian origin. (Letter)</strong>
|
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Clin. Genet. 56: 100-102, 1999.
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[PubMed: 10466427]
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[Full Text: https://doi.org/10.1034/j.1399-0004.1999.560117.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Barneveld, R. A., Keijzer, W., Tegelaers, F. P. W., Ginns, E. I., Geurts van Kessel, A., Brady, R. O., Barranger, J. A., Tager, J. M., Galjaard, H., Westerveld, A., Reuser, A. J. J.
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<strong>Assignment of the gene coding for human beta-glucocerebrosidase to the region q21-q31 of chromosome 1 using monoclonal antibodies.</strong>
|
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Hum. Genet. 64: 227-231, 1983.
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[PubMed: 6885065]
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[Full Text: https://doi.org/10.1007/BF00279398]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Beutler, E., Demina, A., Gelbart, T.
|
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<strong>Glucocerebrosidase mutations in Gaucher disease.</strong>
|
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Molec. Med. 1: 82-92, 1994.
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[PubMed: 8790604]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Beutler, E., Gelbart, T., Demina, A., Zimran, A., LeCoutre, P.
|
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<strong>Five new Gaucher disease mutations.</strong>
|
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Blood Cells Molec. Dis. 21: 20-24, 1995.
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[PubMed: 7655857]
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[Full Text: https://doi.org/10.1006/bcmd.1995.0004]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Beutler, E., Gelbart, T., Kuhl, W., Sorge, J., West, C.
|
|
<strong>Identification of the second common Jewish Gaucher disease mutation makes possible population-based screening for the heterozygous state.</strong>
|
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Proc. Nat. Acad. Sci. 88: 10544-10547, 1991.
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[PubMed: 1961718]
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[Full Text: https://doi.org/10.1073/pnas.88.23.10544]
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|
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</p>
|
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</li>
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<li>
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<p class="mim-text-font">
|
|
Beutler, E., Gelbart, T., Kuhl, W., Zimran, A., West, C.
|
|
<strong>Mutations in Jewish patients with Gaucher disease.</strong>
|
|
Blood 79: 1662-1666, 1992.
|
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[PubMed: 1558964]
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</p>
|
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</li>
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<li>
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<p class="mim-text-font">
|
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Beutler, E., Gelbart, T., West, C.
|
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<strong>Identification of six new Gaucher disease mutations.</strong>
|
|
Genomics 15: 203-205, 1993.
|
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[PubMed: 8432537]
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[Full Text: https://doi.org/10.1006/geno.1993.1035]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Beutler, E., Gelbart, T.
|
|
<strong>Gaucher disease associated with a unique KpnI restriction site: identification of the amino-acid substitution.</strong>
|
|
Ann. Hum. Genet. 54: 149-153, 1990.
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|
|
|
[PubMed: 1974409]
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|
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[Full Text: https://doi.org/10.1111/j.1469-1809.1990.tb00371.x]
|
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Beutler, E., Gelbart, T.
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<strong>Glucocerebrosidase (Gaucher disease).</strong>
|
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Hum. Mutat. 8: 207-213, 1996.
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|
[PubMed: 8889578]
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[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1996)8:3<207::AID-HUMU2>3.0.CO;2-6]
|
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|
|
</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Beutler, E.
|
|
<strong>Gaucher disease: new molecular approaches to diagnosis and treatment.</strong>
|
|
Science 256: 794-799, 1992.
|
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|
|
|
[PubMed: 1589760]
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|
|
[Full Text: https://doi.org/10.1126/science.1589760]
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</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Beutler, E.
|
|
<strong>Gaucher disease as a paradigm of current issues regarding single gene mutations of humans.</strong>
|
|
Proc. Nat. Acad. Sci. 90: 5384-5390, 1993.
|
|
|
|
|
|
[PubMed: 8516282]
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|
|
[Full Text: https://doi.org/10.1073/pnas.90.12.5384]
|
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|
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</p>
|
|
</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Bohlega, S., Kambouris, M., Shahid, M., Al Homsi, M., Al Sous, W.
|
|
<strong>Gaucher disease with oculomotor apraxia and cardiovascular calcification (Gaucher type IIIC).</strong>
|
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Neurology 54: 261-263, 2000.
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|
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[PubMed: 10636167]
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|
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[Full Text: https://doi.org/10.1212/wnl.54.1.261]
|
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|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chabas, A., Cormand, B., Grinberg, D., Burguera, J. M., Balcells, S., Merino, J. L., Mate, I., Sobrino, J. A., Gonzalez-Duarte, R., Vilageliu, L.
|
|
<strong>Unusual expression of Gaucher's disease: cardiovascular calcifications in three sibs homozygous for the D409H mutation.</strong>
|
|
J. Med. Genet. 32: 740-742, 1995.
|
|
|
|
|
|
[PubMed: 8544197]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.32.9.740]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Choudary, P. V., Tsuji, S., Martin, B. M., Guild, B. C., Mulligan, R. C., Murray, G. J., Barranger, J. A., Ginns, E. I.
|
|
<strong>The molecular biology of Gaucher disease and the potential for gene therapy.</strong>
|
|
Cold Spring Harbor Symp. Quant. Biol. 51: 1047-1052, 1986.
|
|
|
|
|
|
[PubMed: 3472751]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/sqb.1986.051.01.121]
|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Cormand, B., Grinberg, D., Gort, L., Chabas, A., Vilageliu, L.
|
|
<strong>Molecular analysis and clinical findings in the Spanish Gaucher disease population: putative haplotype of the N370S ancestral chromosome.</strong>
|
|
Hum. Mutat. 11: 295-305, 1998.
|
|
|
|
|
|
[PubMed: 9554746]
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|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<295::AID-HUMU7>3.0.CO;2-6]
|
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Cormand, B., Montfort, M., Chabas, A., Vilageliu, L., Grinberg, D.
|
|
<strong>Genetic fine localization of the beta-glucocerebrosidase (GBA) and prosaposin (PSAP) genes: implications for Gaucher disease.</strong>
|
|
Hum. Genet. 100: 75-79, 1997.
|
|
|
|
|
|
[PubMed: 9225972]
|
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|
|
[Full Text: https://doi.org/10.1007/s004390050468]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Cormand, B., Vilageliu, L., Burguera, J. M., Balcells, S., Gonzalez-Duarte, R., Grinberg, D., Chabas, A.
|
|
<strong>Gaucher disease in Spanish patients: analysis of eight mutations.</strong>
|
|
Hum. Mutat. 5: 303-309, 1995.
|
|
|
|
|
|
[PubMed: 7627184]
|
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|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380050406]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Dahl, N., Lagerstrom, M., Erikson, A., Pettersson, U.
|
|
<strong>Gaucher disease type III (Norrbottnian type) is caused by a single mutation in exon 10 of the glucocerebrosidase gene.</strong>
|
|
Am. J. Hum. Genet. 47: 275-278, 1990.
|
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|
|
|
|
[PubMed: 2378352]
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Zimran, A., Gelbart, T., Westwood, B., Grabowski, G. A., Beutler, E.
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<strong>High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews.</strong>
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Am. J. Hum. Genet. 49: 855-859, 1991.
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[PubMed: 1897529]
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Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E.
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<strong>Prediction of severity of Gaucher's disease by identification of mutations at DNA level.</strong>
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Lancet 334: 349-352, 1989. Note: Originally Volume 2.
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[PubMed: 2569551]
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[Full Text: https://doi.org/10.1016/s0140-6736(89)90536-9]
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Zimran, A., Sorge, J., Gross, E., Kubitz, M., West, C., Beutler, E.
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<strong>A glucocerebrosidase fusion gene in Gaucher disease: implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder.</strong>
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J. Clin. Invest. 85: 219-222, 1990.
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[PubMed: 2295698]
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[Full Text: https://doi.org/10.1172/JCI114415]
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Bao Lige - updated : 06/13/2018<br>George E. Tiller - updated : 06/21/2017<br>Paul J. Converse - updated : 02/05/2016<br>Cassandra L. Kniffin - updated : 11/5/2013<br>Patricia A. Hartz - updated : 8/7/2013<br>Cassandra L. Kniffin - updated : 4/22/2013<br>Patricia A. Hartz - updated : 2/28/2012<br>Cassandra L. Kniffin - updated : 6/13/2011<br>Cassandra L. Kniffin - updated : 2/19/2010<br>Cassandra L. Kniffin - updated : 11/4/2009<br>Marla J. F. O'Neill - updated : 6/8/2009<br>Cassandra L. Kniffin - updated : 3/16/2009<br>Cassandra L. Kniffin - updated : 10/8/2008<br>Cassandra L. Kniffin - updated : 8/25/2008<br>Cassandra L. Kniffin - updated : 8/12/2008<br>Cassandra L. Kniffin - updated : 4/2/2008<br>Cassandra L. Kniffin - updated : 8/3/2007<br>Cassandra L. Kniffin - updated : 2/19/2007<br>Cassandra L. Kniffin - reorganized : 11/2/2006<br>Cassandra L. Kniffin - updated : 10/2/2006<br>Cassandra L. Kniffin - updated : 4/20/2006<br>Cassandra L. Kniffin - updated : 1/24/2005<br>Marla J. F. O'Neill - updated : 7/20/2004<br>Victor A. McKusick - updated : 6/15/2004<br>Victor A. McKusick - updated : 4/6/2004<br>Victor A. McKusick - updated : 7/18/2003<br>Victor A. McKusick - updated : 2/28/2003<br>Victor A. McKusick - updated : 1/31/2003<br>Victor A. McKusick - updated : 8/19/2002<br>Victor A. McKusick - updated : 5/9/2002
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Ada Hamosh : 11/16/2001
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