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Entry
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- *606890 - GALACTOSYLCERAMIDASE; GALC
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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">*606890</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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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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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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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606890">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 role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000054983;t=ENST00000261304" 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=2581" 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=606890" 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=ENSG00000054983;t=ENST00000261304" 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_000153,NM_001201401,NM_001201402,NM_001424071,NM_001424072,NM_001424073,NM_001424074,NM_001424075,NM_001424076,NM_001424077,NR_187582,XM_047431199" 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_000153" 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=606890" 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=06057&isoform_id=06057_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/GALC" 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/431310,457444,457446,710535,2897771,4321149,22328079,83281450,119601765,119601766,119601767,119601768,194376492,194379654,194381084,194383208,221044202,319655717,319655720,332368235,332368237,1035664365,2217296987,2462539646,2572523490,2572523492,2572523541,2572523554,2572523575,2572523897,2572523913" 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/P54803" 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=2581" 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=ENSG00000054983;t=ENST00000261304" 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=GALC" 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=GALC" 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+2581" 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/GALC" 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:2581" 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/2581" 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=chr14&hgg_gene=ENST00000261304.7&hgg_start=87933014&hgg_end=87993667&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:4115" 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:4115" 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/galc" 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=606890[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=606890[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/GALC/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/ENSG00000054983" 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=GALC" 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=GALC" 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=GALC" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=GALC&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/PA28530" 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:4115" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:95636" 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/GALC#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:95636" 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/2581/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/OMIA000578/" 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=2581" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00016207;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-2115" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2581" 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=GALC&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> 189979005, 192782005<br />
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<strong>ICD10CM:</strong> E75.23<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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606890
|
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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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GALACTOSYLCERAMIDASE; GALC
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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">
|
|
<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>
|
|
<span class="mim-font">
|
|
GALACTOCEREBROSIDASE
|
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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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GALC" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GALC</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/14/434?start=-3&limit=10&highlight=434">14q31.3</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:87933014-87993667&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'})">14:87,933,014-87,993,667</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/14/434?start=-3&limit=10&highlight=434">
|
|
14q31.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Krabbe disease
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/245200"> 245200 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
|
</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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<p>Galactosylceramidase (<a href="https://enzyme.expasy.org/EC/3.2.1.46" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 3.2.1.46</a>) is a lysosomal enzyme involved in the catabolism of galactosylceramide, a major lipid in myelin, kidney, and epithelial cells of the small intestine and colon (<a href="#2" class="mim-tip-reference" title="Chen, Y. Q., Rafi, M. A., de Gala, G., Wenger, D. A. <strong>Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme deficient in globoid cell leukodystrophy.</strong> Hum. Molec. Genet. 2: 1841-1845, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8281145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8281145</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1841" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8281145">Chen et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8281145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#2" class="mim-tip-reference" title="Chen, Y. Q., Rafi, M. A., de Gala, G., Wenger, D. A. <strong>Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme deficient in globoid cell leukodystrophy.</strong> Hum. Molec. Genet. 2: 1841-1845, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8281145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8281145</a>] [<a href="https://doi.org/10.1093/hmg/2.11.1841" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8281145">Chen et al. (1993)</a> cloned the human GALC cDNA by screening human testes and human brain cDNA libraries with a degenerate primer derived from a GALC fragment previously isolated from human urine and brain (<a href="#3" class="mim-tip-reference" title="Chen, Y. Q., Wenger, D. A. <strong>Galactocerebrosidase from human urine: purification and partial characterization.</strong> Biochim. Biophys. Acta 1170: 53-61, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8399327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8399327</a>] [<a href="https://doi.org/10.1016/0005-2760(93)90175-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8399327">Chen and Wenger, 1993</a>). Two overlapping clones containing the total protein coding region were obtained. The open reading frame codes for 669 amino acids, representing a protein with a molecular mass of approximately 73 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8399327+8281145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Sakai, N., Inui, K., Fujii, N., Fukushima, H., Nishimoto, J., Yanagihara, I., Isegawa, Y., Iwamatsu, A., Okada, S. <strong>Krabbe disease: isolation and characterization of a full-length cDNA for human galactocerebrosidase.</strong> Biochem. Biophys. Res. Commun. 198: 485-491, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8297359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8297359</a>] [<a href="https://doi.org/10.1006/bbrc.1994.1071" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8297359">Sakai et al. (1994)</a> purified galactocerebrosidase from human lymphocytes and cloned the corresponding cDNA. The cDNA encodes a single chain peptide with a 26-amino acid N-terminal signal peptide and 6 potential asparagine-linked glycosylation sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8297359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Victoria, T., Rafi, M. A., Wenger, D. A. <strong>Cloning of the canine GALC cDNA and identification of the mutation causing globoid cell leukodystrophy in West Highland White and Cairn terriers.</strong> Genomics 33: 457-462, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661004</a>] [<a href="https://doi.org/10.1006/geno.1996.0220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661004">Victoria et al. (1996)</a> cloned the canine GALC cDNA and demonstrated that the deduced amino acid sequence is about 90% identical to that of the human protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Luzi, P., Rafi, M. A., Victoria, T., Baskin, G. B., Wenger, D. A. <strong>Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate.</strong> Genomics 42: 319-324, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9192853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9192853</a>] [<a href="https://doi.org/10.1006/geno.1997.4744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9192853">Luzi et al. (1997)</a> described the cloning of the GALC cDNA and gene from the rhesus monkey. The gene organization was nearly identical to that of the human gene, and the deduced amino acid sequence of monkey GALC was about 97%, 87%, and 83% identical to that in human, dog, and mouse, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9192853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al. (2010)</a> noted that translation initiation at alternative ATG codons in GALC give rise to protein precursors with 42-residue and 26-residue leader sequences, respectively. Both precursors are processed to the 669-residue mature enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#13" class="mim-tip-reference" title="Luzi, P., Rafi, M. A., Wenger, D. A. <strong>Structure and organization of the human galactocerebrosidase (GALC) gene.</strong> Genomics 26: 407-409, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7601472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7601472</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80230-j" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7601472">Luzi et al. (1995)</a> determined that the human GALC gene contains 17 exons spanning about 60 kb of genomic DNA. GALC has a GC-rich promoter region similar to the genes of other lysosomal proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7601472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By isotopic in situ hybridization, <a href="#1" class="mim-tip-reference" title="Cannizzaro, L. A., Chen, Y. Q., Rafi, M. A., Wenger, D. A. <strong>Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization.</strong> Cytogenet. Cell Genet. 66: 244-245, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8162701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8162701</a>] [<a href="https://doi.org/10.1159/000133703" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8162701">Cannizzaro et al. (1994)</a> mapped the GALC gene to chromosome 14q31. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8162701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By 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="#9" 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 (<a href="/entry/606463">606463</a>), GALC, 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>
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<p><a href="#18" class="mim-tip-reference" title="Sakai, N., Inui, K., Fujii, N., Fukushima, H., Nishimoto, J., Yanagihara, I., Isegawa, Y., Iwamatsu, A., Okada, S. <strong>Krabbe disease: isolation and characterization of a full-length cDNA for human galactocerebrosidase.</strong> Biochem. Biophys. Res. Commun. 198: 485-491, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8297359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8297359</a>] [<a href="https://doi.org/10.1006/bbrc.1994.1071" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8297359">Sakai et al. (1994)</a> identified homozygosity for a nonsense mutation (E385X; <a href="#0001">606890.0001</a>) in a patient with typical Krabbe disease (KRB; <a href="/entry/245200">245200</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8297359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Rafi, M. A., Luzi, P., Chen, Y. Q., Wenger, D. A. <strong>A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease.</strong> Hum. Molec. Genet. 4: 1285-1289, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581365</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581365">Rafi et al. (1995)</a> analyzed the GALC gene in 2 patients with infantile Krabbe disease and identified homozygosity for a 30-kb deletion (<a href="#0002">606890.0002</a>) that was found to be associated with a 502C-T transition on the same allele, which they designated '502/del.' The transition was determined to be a polymorphism. Expression of the 502/del mutation in COS-1 cells resulted in no measurable GALC activity above that in mock-transfected cells. <a href="#15" class="mim-tip-reference" title="Rafi, M. A., Luzi, P., Chen, Y. Q., Wenger, D. A. <strong>A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease.</strong> Hum. Molec. Genet. 4: 1285-1289, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581365</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581365">Rafi et al. (1995)</a> studied an additional 46 patients with infantile Krabbe disease and identified 8 who were homozygous for the 502/del allele and 5 who were compound heterozygotes for the 502/del allele and a second mutant allele, the latter including 3 missense mutations and 1 single nucleotide insertion which had not yet been confirmed by expression studies. The authors noted that 11 patients did not have the 502 polymorphism, but that no patient was found with the deletion who did not carry the 502 polymorphism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="De Gasperi, R., Gama Sosa, M. A., Sartorato, E. L., Battistini, S., MacFarlane, H., Gusella, J. F., Krivit, W., Kolodny, E. H. <strong>Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy.</strong> Am. J. Hum. Genet. 59: 1233-1242, 1996. Note: Erratum: Am. J. Hum. Genet. 60: 1264 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940268</a>]" pmid="8940268">De Gasperi et al. (1996)</a> analyzed the galactocerebrosidase gene in 9 families with late-onset globoid cell leukoencephalopathy (GLD) and in 1 patient with classic Krabbe disease. They reported that 5 of the patients were compound heterozygotes for the 30-kb deletion (<a href="#0002">606890.0002</a>) first reported by <a href="#15" class="mim-tip-reference" title="Rafi, M. A., Luzi, P., Chen, Y. Q., Wenger, D. A. <strong>A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease.</strong> Hum. Molec. Genet. 4: 1285-1289, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581365</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581365">Rafi et al. (1995)</a> and another mutation in the GALC gene. <a href="#4" class="mim-tip-reference" title="De Gasperi, R., Gama Sosa, M. A., Sartorato, E. L., Battistini, S., MacFarlane, H., Gusella, J. F., Krivit, W., Kolodny, E. H. <strong>Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy.</strong> Am. J. Hum. Genet. 59: 1233-1242, 1996. Note: Erratum: Am. J. Hum. Genet. 60: 1264 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940268</a>]" pmid="8940268">De Gasperi et al. (1996)</a> identified 6 missense mutations: R63H, G95S, M101L, G268S, Y298C, and I234T. They also identified a nonsense mutation (S7X), a 1-bp deletion mutation (805delG), a mutation that interferes with splicing of intron 1, and a 34-nucleotide insertion in the RNA caused by the aberrant splicing of intron 6. Most of the novel mutations identified appeared to be private family mutations. In an erratum, <a href="#4" class="mim-tip-reference" title="De Gasperi, R., Gama Sosa, M. A., Sartorato, E. L., Battistini, S., MacFarlane, H., Gusella, J. F., Krivit, W., Kolodny, E. H. <strong>Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy.</strong> Am. J. Hum. Genet. 59: 1233-1242, 1996. Note: Erratum: Am. J. Hum. Genet. 60: 1264 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940268</a>]" pmid="8940268">De Gasperi et al. (1996)</a> stated that the loss of a restriction site in exon 8 of the GALC gene in families 2 and 3 with GLD was not due to the 805delG substitution but to an 809G-A transition resulting in a G270D missense mutation; the 805delG substitution identified in 1 member of family 2 led to loss of the same restriction site but the significance of the change was uncertain. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8940268+7581365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 different inbred communities in Israel with Krabbe disease, <a href="#16" class="mim-tip-reference" title="Rafi, M. A., Luzi, P., Zlotogora, J., Wenger, D. A. <strong>Two different mutations are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel.</strong> Hum. Genet. 97: 304-308, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8786069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8786069</a>] [<a href="https://doi.org/10.1007/BF02185759" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8786069">Rafi et al. (1996)</a> identified 2 different founder mutations in the GALC gene: one in a Moslem Arab population (<a href="#0003">606890.0003</a>) and one in a Druze population (<a href="#0004">606890.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8786069" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 4 Japanese patients with adult-onset Krabbe disease, <a href="#7" class="mim-tip-reference" title="Furuya, H., Kukita, Y., Nagano, S., Sakai, Y., Yamashita, Y., Fukuyama, H., Inatomi, Y., Saito, Y., Koike, R., Tsuji, S., Fukumaki, Y., Hayashi, K., Kobayashi, T. <strong>Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients.</strong> Hum. Genet. 100: 450-456, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9272171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9272171</a>] [<a href="https://doi.org/10.1007/s004390050532" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9272171">Furuya et al. (1997)</a> identified 4 novel mutations in the GALC gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9272171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#22" class="mim-tip-reference" title="Xu, C., Sakai, N., Taniike, M., Inui, K., Ozono, K. <strong>Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation.</strong> J. Hum. Genet. 51: 548-554, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16607461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16607461</a>] [<a href="https://doi.org/10.1007/s10038-006-0396-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16607461">Xu et al. (2006)</a> investigated mutations of the GALC gene in 17 unrelated Japanese patients with Krabbe disease and reviewed the mutations previously reported in 11 Japanese patients. The authors found that 12del3ins and I66M + I289V, which had been identified only in Japanese individuals to date, accounted for 37% of the mutant alleles; with 2 additional mutations, G270D and T652P, these accounted for up to 57% of mutations in Japanese patients. <a href="#22" class="mim-tip-reference" title="Xu, C., Sakai, N., Taniike, M., Inui, K., Ozono, K. <strong>Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation.</strong> J. Hum. Genet. 51: 548-554, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16607461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16607461</a>] [<a href="https://doi.org/10.1007/s10038-006-0396-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16607461">Xu et al. (2006)</a> observed a tendency for the I66M + I289V, G270D, and L618S mutations to be associated with a mild phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16607461" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 30 unrelated Italian patients with Krabbe disease, <a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al. (2010)</a> identified 33 different mutations in the GALC gene, including 14 novel mutations (see, e.g., <a href="#0005">606890.0005</a>-<a href="#0009">606890.0009</a>). The 15 novel mutations included 4 missense mutations in highly conserved residues, 7 frameshift mutations, 3 nonsense mutations, and 1 splice site mutation. Thus, 73% of the newly described mutations were expected to affect mRNA processing. In silico analysis predicted that the missense mutations had a high probability of being deleterious. The common 30-kb deletion (<a href="#0002">606890.0002</a>) accounted for 18% of mutant alleles, and 4 patients had a founder mutation (G553R; <a href="#0005">606890.0005</a>). Otherwise, most of the mutations were private. There were no clear genotype-phenotype correlations, but some missense mutations were associated with milder phenotypes (see, e.g., G286D; <a href="#0008">606890.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#21" class="mim-tip-reference" title="Victoria, T., Rafi, M. A., Wenger, D. A. <strong>Cloning of the canine GALC cDNA and identification of the mutation causing globoid cell leukodystrophy in West Highland White and Cairn terriers.</strong> Genomics 33: 457-462, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661004</a>] [<a href="https://doi.org/10.1006/geno.1996.0220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661004">Victoria et al. (1996)</a> found that the disease-causing mutation in the canine GALC gene was demonstrated to be an A-to-C transversion at cDNA position 473 (Y158S). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Luzi, P., Rafi, M. A., Victoria, T., Baskin, G. B., Wenger, D. A. <strong>Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate.</strong> Genomics 42: 319-324, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9192853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9192853</a>] [<a href="https://doi.org/10.1006/geno.1997.4744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9192853">Luzi et al. (1997)</a> found that the mutation causing GLD in the rhesus monkey was a deletion of AC corresponding to cDNA positions 387 and 388 in exon 4. This resulted in a frameshift and stop codon after 46 nucleotides. Using an engineered sense primer and an antisense primer from intron 4, <a href="#11" class="mim-tip-reference" title="Luzi, P., Rafi, M. A., Victoria, T., Baskin, G. B., Wenger, D. A. <strong>Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate.</strong> Genomics 42: 319-324, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9192853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9192853</a>] [<a href="https://doi.org/10.1006/geno.1997.4744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9192853">Luzi et al. (1997)</a> developed a rapid method to detect the GALC mutation. When 45 monkeys from 1 colony were tested, 22 were found to be carriers. The availability of this nonhuman primate model of GLD provides unique opportunities to evaluate treatment for this severe disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9192853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606890[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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<p>In a patient with typical Krabbe disease (KRB; <a href="/entry/245200">245200</a>), <a href="#18" class="mim-tip-reference" title="Sakai, N., Inui, K., Fujii, N., Fukushima, H., Nishimoto, J., Yanagihara, I., Isegawa, Y., Iwamatsu, A., Okada, S. <strong>Krabbe disease: isolation and characterization of a full-length cDNA for human galactocerebrosidase.</strong> Biochem. Biophys. Res. Commun. 198: 485-491, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8297359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8297359</a>] [<a href="https://doi.org/10.1006/bbrc.1994.1071" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8297359">Sakai et al. (1994)</a> identified homozygosity for a GAA-to-TAA mutation in codon 385, predicting a glu385-to-ter (E385X) substitution. This mutation, originally reported as GLU369TER, has been renumbered based on the first ATG initiation codon as nucleotide +1 (<a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20886637+8297359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>.0002 KRABBE DISEASE</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004023" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004023" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004023</a>
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<p><a href="#15" class="mim-tip-reference" title="Rafi, M. A., Luzi, P., Chen, Y. Q., Wenger, D. A. <strong>A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease.</strong> Hum. Molec. Genet. 4: 1285-1289, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581365</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581365">Rafi et al. (1995)</a> analyzed the GALC gene in 2 patients with infantile Krabbe disease and identified homozygosity for a deletion of exons 11-17 that was found to be associated with a 502C-T transition on the same allele, which they designated '502/del.' The transition was later determined to be a polymorphism. Expression of the 502/del mutation in COS-1 cells resulted in no measurable GALC activity above that in mock-transfected cells. <a href="#15" class="mim-tip-reference" title="Rafi, M. A., Luzi, P., Chen, Y. Q., Wenger, D. A. <strong>A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease.</strong> Hum. Molec. Genet. 4: 1285-1289, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581365</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581365">Rafi et al. (1995)</a> studied an additional 46 patients with infantile Krabbe disease and identified 8 who were homozygous for the 502/del allele and 5 who were compound heterozygotes for 502/del allele and a second mutant allele. There were 21 patients who were heterozygous and 1 who was homozygous for the 502 polymorphism in whom the presence of the deletion could not be confirmed, but no patient was found with the deletion who did not carry the 502 polymorphism. <a href="#12" class="mim-tip-reference" title="Luzi, P., Rafi, M. A., Wenger, D. A. <strong>Characterization of the large deletion in the GALC gene found in patients with Krabbe disease.</strong> Hum. Molec. Genet. 4: 2335-2338, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634707</a>] [<a href="https://doi.org/10.1093/hmg/4.12.2335" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8634707">Luzi et al. (1995)</a> determined that the deletion is approximately 30 kb starting near the middle of intron 10 and including all of the coding region through exon 17 plus an additional 9 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7581365+8634707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="De Gasperi, R., Gama Sosa, M. A., Sartorato, E. L., Battistini, S., MacFarlane, H., Gusella, J. F., Krivit, W., Kolodny, E. H. <strong>Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy.</strong> Am. J. Hum. Genet. 59: 1233-1242, 1996. Note: Erratum: Am. J. Hum. Genet. 60: 1264 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940268</a>]" pmid="8940268">De Gasperi et al. (1996)</a> analyzed the GALC gene in 9 families with late-onset globoid cell leukoencephalopathy and in 1 patient with classic Krabbe disease and found that 5 of the patients were compound heterozygotes for the 30-kb deletion first reported by <a href="#15" class="mim-tip-reference" title="Rafi, M. A., Luzi, P., Chen, Y. Q., Wenger, D. A. <strong>A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease.</strong> Hum. Molec. Genet. 4: 1285-1289, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581365</a>] [<a href="https://doi.org/10.1093/hmg/4.8.1285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7581365">Rafi et al. (1995)</a> and another mutation in the GALC gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8940268+7581365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Kleijer, W. J., Keulemans, J. L. M., van der Kraan, M., Geilen, G. G., van der Helm, R. M., Rafi, M. A., Luzi, P., Wenger, D. A., Halley, D. J. J., van Diggelen, O. P. <strong>Prevalent mutations in the GALC gene of patients with Krabbe disease of Dutch and other European origin.</strong> J. Inherit. Metab. Dis. 20: 587-594, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266397</a>] [<a href="https://doi.org/10.1023/a:1005315311165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9266397">Kleijer et al. (1997)</a> found that the 30-kb deletion was present in 52% of mutant alleles from 41 Dutch patients with Krabbe disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al. (2010)</a> found the 30-kb deletion in 18% of disease alleles among their cohort of 30 Italian patients. They stated that the 502C-T transition has been renumbered as 550C-T based on the first ATG initiation codon as nucleotide +1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 KRABBE DISEASE</strong>
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GALC, ASP544ASN
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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> rs387906952 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906952;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/rs387906952?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=rs387906952" 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=rs387906952" 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=RCV000023588 OR RCV001270016" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023588, RCV001270016" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023588...</a>
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<p>In affected individuals from an inbred Arab Israeli population with infantile Krabbe disease (KRB; <a href="/entry/245200">245200</a>), <a href="#16" class="mim-tip-reference" title="Rafi, M. A., Luzi, P., Zlotogora, J., Wenger, D. A. <strong>Two different mutations are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel.</strong> Hum. Genet. 97: 304-308, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8786069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8786069</a>] [<a href="https://doi.org/10.1007/BF02185759" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8786069">Rafi et al. (1996)</a> identified a homozygous 1630G-A transition in exon 14 of the GALC gene, resulting in an asp544-to-asn (D544N) substitution in the 30-kD subunit. The findings were consistent with a founder effect. In vitro functional expression studies showed that the mutant protein had no enzymatic activity. This mutation, originally reported as ASP528ASN, has been renumbered based on the first ATG initiation codon as nucleotide +1 (<a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8786069+20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 KRABBE DISEASE</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">rs387906953 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906953;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=rs387906953" 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=rs387906953" 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=RCV000023589" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023589" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023589</a>
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<p>In affected individuals from an inbred Druze population in northern Israel with infantile Krabbe disease (KRB; <a href="/entry/245200">245200</a>), <a href="#16" class="mim-tip-reference" title="Rafi, M. A., Luzi, P., Zlotogora, J., Wenger, D. A. <strong>Two different mutations are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel.</strong> Hum. Genet. 97: 304-308, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8786069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8786069</a>] [<a href="https://doi.org/10.1007/BF02185759" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8786069">Rafi et al. (1996)</a> identified a homozygous 1796T-G transversion in exon 15 of the GALC gene, resulting in an ile599-to-ser (I599S) substitution in the 30-kD subunit. The findings were consistent with a founder effect. In vitro functional expression studies showed that the mutant protein had no enzymatic activity. This mutation, originally reported as ILE583SER, has been renumbered based on the first ATG initiation codon as nucleotide +1 (<a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8786069+20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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GALC, GLY553ARG
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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> rs748573754 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs748573754;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/rs748573754?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=rs748573754" 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=rs748573754" 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=RCV000169525 OR RCV003137698" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000169525, RCV003137698" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000169525...</a>
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<p>In patients with Krabbe disease (KRB; <a href="/entry/245200">245200</a>), <a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al. (2010)</a> identified a 1657G-A transition in exon 14 of the GALC gene, resulting in a gly553-to-arg (G553R) substitution. The G553R mutation was found in 7 Italian patients from southern Italy, and haplotype analysis indicated a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 KRABBE DISEASE</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">rs2139956292 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2139956292;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=rs2139956292" 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=rs2139956292" 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=RCV000023591" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023591" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023591</a>
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<p>In an Italian patient with classic Krabbe disease (KRB; <a href="/entry/245200">245200</a>), <a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al. (2010)</a> identified compound heterozygosity for 2 mutations in the GALC gene: a G-to-A transition (1489+1G-A) in intron 13, demonstrated to cause partial skipping of exon 13 and premature termination, and a 1-bp deletion (1901delT; <a href="#0007">606890.0007</a>), also predicted to result in premature termination. The patient presented at age 5 months with truncal hypotonia, hypertonia, spasticity, and white matter changes. Residual GALC activity was 9.7% of control levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 KRABBE DISEASE</strong>
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GALC, 1-BP DEL, 1901T
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555378534 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555378534;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=rs1555378534" 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=rs1555378534" 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=RCV000670467" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000670467" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000670467</a>
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<p>For discussion of the 1-bp deletion (1901delT) in the GALC gene that was identified in compound heterozygous state in a patient with Krabbe disease (KRB; <a href="/entry/245200">245200</a>) by <a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al. (2010)</a>, see <a href="#0006">606890.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 KRABBE DISEASE</strong>
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GALC, GLY286ASP
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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> rs199847983 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199847983;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/rs199847983?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=rs199847983" 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=rs199847983" 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=RCV000023593 OR RCV000363446" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023593, RCV000363446" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023593...</a>
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<p>In an Italian patient with juvenile onset of Krabbe disease (KRB; <a href="/entry/245200">245200</a>) at age 4 years, <a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al. (2010)</a> identified compound heterozygosity for 2 mutations in the GALC gene: an 857G-A transition in exon 8, resulting in a gly286-to-asp (G286D) substitution in a highly conserved residue, and the common 30-kb deletion (<a href="#0002">606890.0002</a>). An unrelated patient with onset of Krabbe disease at age 26 was compound heterozygous for the G286D mutation and a 953C-G transversion in exon 9, resulting in a pro318-to-arg (P318R; <a href="#0009">606890.0009</a>) substitution in a highly conserved residue. <a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al. (2010)</a> speculated that the G286D mutation may be a mild lesion resulting in a less severe phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 KRABBE DISEASE</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> rs387906954 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906954;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/rs387906954?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=rs387906954" 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=rs387906954" 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=RCV000023594" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023594" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023594</a>
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<p>See <a href="#0008">606890.0008</a> and <a href="#20" class="mim-tip-reference" title="Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M. <strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong> Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21367" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20886637">Tappino et al. (2010)</a> <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 KRABBE DISEASE</strong>
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GALC, GLY41SER
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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> rs387906955 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906955;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/rs387906955?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=rs387906955" 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=rs387906955" 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=RCV000023595" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023595" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023595</a>
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<p><a href="#6" class="mim-tip-reference" title="Fiumara, A., Barone, R., Arena, A., Filocamo, M., Lissens, W., Pavone, L., Sorge, G. <strong>Krabbe leukodystrophy in a selected population with high rate of late onset forms: longer survival linked to c.121G-A (p.gly41ser) mutation.</strong> Clin. Genet. 80: 452-458, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21070211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21070211</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01572.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21070211">Fiumara et al. (2011)</a> identified a 121G-A transition in the GALC gene, resulting in a gly41-to-ser (G41S) substitution, as a founder mutation for Krabbe disease (KRB; <a href="/entry/245200">245200</a>) among Sicilian Italians from the region of Catania. The mutation was enriched among 17 patients with onset of disease after age 6 months. Among the 4 patients who were homozygous for the mutation, enzyme activity ranged between 1 and 6% of controls, but there was no correlation between enzyme activity and age at onset or disease course. However, <a href="#6" class="mim-tip-reference" title="Fiumara, A., Barone, R., Arena, A., Filocamo, M., Lissens, W., Pavone, L., Sorge, G. <strong>Krabbe leukodystrophy in a selected population with high rate of late onset forms: longer survival linked to c.121G-A (p.gly41ser) mutation.</strong> Clin. Genet. 80: 452-458, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21070211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21070211</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2010.01572.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21070211">Fiumara et al. (2011)</a> concluded that the G41S mutation is associated with a protracted course of the disorder, although patients were significantly disabled. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21070211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#Duchen1980" class="mim-tip-reference" title="Duchen, L. W., Eicher, E. M., Jacobs, J. M., Scaravilli, F., Teixeira, F. <strong>Hereditary leucodystrophy in the mouse: the new mutant twitcher.</strong> Brain 103: 695-710, 1980.">Duchen et al. (1980)</a>; <a href="#Kodama1982" class="mim-tip-reference" title="Kodama, S., Igisu, H., Siegel, D. A., Suzuki, K. <strong>Glycosylceramide synthesis in the developing spinal cord and kidney of the twitcher mouse, an enzymatically authentic model of human Krabbe disease.</strong> J. Neurochem. 39: 1314-1318, 1982.">Kodama et al. (1982)</a>; <a href="#Lyerla1989" class="mim-tip-reference" title="Lyerla, T. A., Konola, J. T., Skiba, M. C., Raghavan, S. <strong>Galactocerebrosidase activity in somatic cell hybrids derived from twitcher mouse/control human fibroblasts is associated with human chromosome 17.</strong> Am. J. Hum. Genet. 44: 198-207, 1989.">Lyerla et al. (1989)</a>; <a href="#Rushton1977" class="mim-tip-reference" title="Rushton, A. R., Dawson, G. <strong>Genetic linkage studies of the human glycosphingolipid beta-galactosidases.</strong> Biochem. Genet. 15: 1071-1082, 1977.">Rushton and Dawson (1977)</a>; <a href="#Sweet1986" class="mim-tip-reference" title="Sweet, H. <strong>Twitcher (twi) is on chromosome 12.</strong> Mouse Newsletter 75: 30, 1986.">Sweet (1986)</a>; <a href="#Zlotogora1990" class="mim-tip-reference" title="Zlotogora, J., Chakraborty, S., Knowlton, R. G., Wenger, D. A. <strong>Krabbe disease locus mapped to chromosome 14 by genetic linkage.</strong> Am. J. Hum. Genet. 47: 37-44, 1990.">Zlotogora et al. (1990)</a>; <a href="#Zlotogora1985" class="mim-tip-reference" title="Zlotogora, J., Regev, R., Zeigler, M., Iancu, T. C., Bach, G. <strong>Krabbe disease: increased incidence in a highly inbred community.</strong> Am. J. Med. Genet. 21: 765-770, 1985.">Zlotogora et al. (1985)</a>
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<a id="1" class="mim-anchor"></a>
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<a id="Cannizzaro1994" class="mim-anchor"></a>
|
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|
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Cannizzaro, L. A., Chen, Y. Q., Rafi, M. A., Wenger, D. A.
|
|
<strong>Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 66: 244-245, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8162701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8162701</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8162701" 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/10.1159/000133703" target="_blank">Full Text</a>]
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Chen, Y. Q., Rafi, M. A., de Gala, G., Wenger, D. A.
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<strong>Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme deficient in globoid cell leukodystrophy.</strong>
|
|
Hum. Molec. Genet. 2: 1841-1845, 1993.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8281145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8281145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8281145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/2.11.1841" target="_blank">Full Text</a>]
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<a id="Chen1993" class="mim-anchor"></a>
|
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Chen, Y. Q., Wenger, D. A.
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<strong>Galactocerebrosidase from human urine: purification and partial characterization.</strong>
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Biochim. Biophys. Acta 1170: 53-61, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8399327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8399327</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8399327" 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/10.1016/0005-2760(93)90175-9" target="_blank">Full Text</a>]
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De Gasperi, R., Gama Sosa, M. A., Sartorato, E. L., Battistini, S., MacFarlane, H., Gusella, J. F., Krivit, W., Kolodny, E. H.
|
|
<strong>Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy.</strong>
|
|
Am. J. Hum. Genet. 59: 1233-1242, 1996. Note: Erratum: Am. J. Hum. Genet. 60: 1264 only, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8940268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8940268</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8940268" 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="Duchen1980" class="mim-anchor"></a>
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<p class="mim-text-font">
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Duchen, L. W., Eicher, E. M., Jacobs, J. M., Scaravilli, F., Teixeira, F.
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<strong>Hereditary leucodystrophy in the mouse: the new mutant twitcher.</strong>
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Brain 103: 695-710, 1980.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7417782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7417782</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7417782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/103.3.695" target="_blank">Full Text</a>]
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Fiumara, A., Barone, R., Arena, A., Filocamo, M., Lissens, W., Pavone, L., Sorge, G.
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<strong>Krabbe leukodystrophy in a selected population with high rate of late onset forms: longer survival linked to c.121G-A (p.gly41ser) mutation.</strong>
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Clin. Genet. 80: 452-458, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21070211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21070211</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21070211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2010.01572.x" target="_blank">Full Text</a>]
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Furuya, H., Kukita, Y., Nagano, S., Sakai, Y., Yamashita, Y., Fukuyama, H., Inatomi, Y., Saito, Y., Koike, R., Tsuji, S., Fukumaki, Y., Hayashi, K., Kobayashi, T.
|
|
<strong>Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients.</strong>
|
|
Hum. Genet. 100: 450-456, 1997.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9272171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9272171</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9272171" 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/s004390050532" target="_blank">Full Text</a>]
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Kleijer, W. J., Keulemans, J. L. M., van der Kraan, M., Geilen, G. G., van der Helm, R. M., Rafi, M. A., Luzi, P., Wenger, D. A., Halley, D. J. J., van Diggelen, O. P.
|
|
<strong>Prevalent mutations in the GALC gene of patients with Krabbe disease of Dutch and other European origin.</strong>
|
|
J. Inherit. Metab. Dis. 20: 587-594, 1997.
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|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266397</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266397" 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/10.1023/a:1005315311165" target="_blank">Full Text</a>]
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<a id="Koberlin2015" class="mim-anchor"></a>
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Koberlin, M. S., Snijder, B., Heinz, L. X., Baumann, C. L., Fauster, A., Vladimer, G. I., Gavin, A.-C., Superti-Furga, G.
|
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<strong>A conserved circular network of coregulated lipids modulates innate immune responses.</strong>
|
|
Cell 162: 170-183, 2015.
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[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://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'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.cell.2015.05.051" target="_blank">Full Text</a>]
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Kodama, S., Igisu, H., Siegel, D. A., Suzuki, K.
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<strong>Glycosylceramide synthesis in the developing spinal cord and kidney of the twitcher mouse, an enzymatically authentic model of human Krabbe disease.</strong>
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J. Neurochem. 39: 1314-1318, 1982.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6811701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6811701</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6811701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1471-4159.1982.tb12572.x" target="_blank">Full Text</a>]
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Luzi, P., Rafi, M. A., Victoria, T., Baskin, G. B., Wenger, D. A.
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<strong>Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate.</strong>
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Genomics 42: 319-324, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9192853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9192853</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9192853" 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/geno.1997.4744" target="_blank">Full Text</a>]
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|
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<a id="Luzi1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
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|
Luzi, P., Rafi, M. A., Wenger, D. A.
|
|
<strong>Characterization of the large deletion in the GALC gene found in patients with Krabbe disease.</strong>
|
|
Hum. Molec. Genet. 4: 2335-2338, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8634707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8634707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8634707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/4.12.2335" target="_blank">Full Text</a>]
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<a id="Luzi1995" class="mim-anchor"></a>
|
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<div class="">
|
|
<p class="mim-text-font">
|
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Luzi, P., Rafi, M. A., Wenger, D. A.
|
|
<strong>Structure and organization of the human galactocerebrosidase (GALC) gene.</strong>
|
|
Genomics 26: 407-409, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7601472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7601472</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7601472" 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/10.1016/0888-7543(95)80230-j" target="_blank">Full Text</a>]
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<a id="Lyerla1989" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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Lyerla, T. A., Konola, J. T., Skiba, M. C., Raghavan, S.
|
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<strong>Galactocerebrosidase activity in somatic cell hybrids derived from twitcher mouse/control human fibroblasts is associated with human chromosome 17.</strong>
|
|
Am. J. Hum. Genet. 44: 198-207, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2912067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2912067</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2912067" 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="Rafi1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Rafi, M. A., Luzi, P., Chen, Y. Q., Wenger, D. A.
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<strong>A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease.</strong>
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Hum. Molec. Genet. 4: 1285-1289, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7581365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7581365</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/4.8.1285" target="_blank">Full Text</a>]
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|
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<a id="16" class="mim-anchor"></a>
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<a id="Rafi1996" class="mim-anchor"></a>
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<p class="mim-text-font">
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Rafi, M. A., Luzi, P., Zlotogora, J., Wenger, D. A.
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<strong>Two different mutations are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel.</strong>
|
|
Hum. Genet. 97: 304-308, 1996.
|
|
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8786069/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8786069</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8786069" 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/BF02185759" target="_blank">Full Text</a>]
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<a id="Rushton1977" class="mim-anchor"></a>
|
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<div class="">
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<p class="mim-text-font">
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Rushton, A. R., Dawson, G.
|
|
<strong>Genetic linkage studies of the human glycosphingolipid beta-galactosidases.</strong>
|
|
Biochem. Genet. 15: 1071-1082, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/414740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">414740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=414740" 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/BF00484498" target="_blank">Full Text</a>]
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<a id="Sakai1994" class="mim-anchor"></a>
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Sakai, N., Inui, K., Fujii, N., Fukushima, H., Nishimoto, J., Yanagihara, I., Isegawa, Y., Iwamatsu, A., Okada, S.
|
|
<strong>Krabbe disease: isolation and characterization of a full-length cDNA for human galactocerebrosidase.</strong>
|
|
Biochem. Biophys. Res. Commun. 198: 485-491, 1994.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8297359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8297359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8297359" 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/bbrc.1994.1071" target="_blank">Full Text</a>]
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<a id="Sweet1986" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sweet, H.
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<strong>Twitcher (twi) is on chromosome 12.</strong>
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Mouse Newsletter 75: 30, 1986.
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<a id="Tappino2010" class="mim-anchor"></a>
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Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M.
|
|
<strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong>
|
|
Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20886637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20886637</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20886637[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=20886637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.21367" target="_blank">Full Text</a>]
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Victoria, T., Rafi, M. A., Wenger, D. A.
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<strong>Cloning of the canine GALC cDNA and identification of the mutation causing globoid cell leukodystrophy in West Highland White and Cairn terriers.</strong>
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Genomics 33: 457-462, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661004" 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/geno.1996.0220" target="_blank">Full Text</a>]
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<a id="Xu2006" class="mim-anchor"></a>
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Xu, C., Sakai, N., Taniike, M., Inui, K., Ozono, K.
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<strong>Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation.</strong>
|
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J. Hum. Genet. 51: 548-554, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16607461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16607461</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16607461" 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/s10038-006-0396-3" target="_blank">Full Text</a>]
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<a id="Zlotogora1990" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zlotogora, J., Chakraborty, S., Knowlton, R. G., Wenger, D. A.
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<strong>Krabbe disease locus mapped to chromosome 14 by genetic linkage.</strong>
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Am. J. Hum. Genet. 47: 37-44, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1971996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1971996</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1971996" 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="Zlotogora1985" class="mim-anchor"></a>
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<div class="">
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Zlotogora, J., Regev, R., Zeigler, M., Iancu, T. C., Bach, G.
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<strong>Krabbe disease: increased incidence in a highly inbred community.</strong>
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Am. J. Med. Genet. 21: 765-770, 1985.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4025402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4025402</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4025402" 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.1320210420" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Paul J. Converse - updated : 02/05/2016
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/27/2011<br>Marla J. F. O'Neill - updated : 12/12/2006
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Creation Date:
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Cassandra L. Kniffin : 4/29/2002
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carol : 05/11/2022
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carol : 10/22/2021<br>mgross : 02/05/2016<br>carol : 9/5/2013<br>carol : 7/3/2012<br>carol : 4/6/2012<br>carol : 10/28/2011<br>ckniffin : 10/27/2011<br>carol : 8/26/2011<br>terry : 7/19/2011<br>terry : 7/14/2011<br>wwang : 7/7/2011<br>ckniffin : 6/22/2011<br>wwang : 7/30/2007<br>wwang : 12/14/2006<br>terry : 12/12/2006<br>carol : 12/7/2006<br>carol : 5/1/2002<br>ckniffin : 5/1/2002<br>ckniffin : 4/30/2002<br>ckniffin : 4/30/2002
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<strong>*</strong> 606890
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GALACTOSYLCERAMIDASE; GALC
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GALACTOCEREBROSIDASE
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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: GALC</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> 189979005, 192782005;
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<strong>ICD10CM:</strong> E75.23;
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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: 14q31.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 14:87,933,014-87,993,667 </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="1">
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<span class="mim-font">
|
|
14q31.3
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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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Krabbe disease
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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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245200
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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">
|
|
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">
|
|
<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>Galactosylceramidase (EC 3.2.1.46) is a lysosomal enzyme involved in the catabolism of galactosylceramide, a major lipid in myelin, kidney, and epithelial cells of the small intestine and colon (Chen et al., 1993). </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>Chen et al. (1993) cloned the human GALC cDNA by screening human testes and human brain cDNA libraries with a degenerate primer derived from a GALC fragment previously isolated from human urine and brain (Chen and Wenger, 1993). Two overlapping clones containing the total protein coding region were obtained. The open reading frame codes for 669 amino acids, representing a protein with a molecular mass of approximately 73 kD. </p><p>Sakai et al. (1994) purified galactocerebrosidase from human lymphocytes and cloned the corresponding cDNA. The cDNA encodes a single chain peptide with a 26-amino acid N-terminal signal peptide and 6 potential asparagine-linked glycosylation sites. </p><p>Victoria et al. (1996) cloned the canine GALC cDNA and demonstrated that the deduced amino acid sequence is about 90% identical to that of the human protein. </p><p>Luzi et al. (1997) described the cloning of the GALC cDNA and gene from the rhesus monkey. The gene organization was nearly identical to that of the human gene, and the deduced amino acid sequence of monkey GALC was about 97%, 87%, and 83% identical to that in human, dog, and mouse, respectively. </p><p>Tappino et al. (2010) noted that translation initiation at alternative ATG codons in GALC give rise to protein precursors with 42-residue and 26-residue leader sequences, respectively. Both precursors are processed to the 669-residue mature enzyme. </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>Luzi et al. (1995) determined that the human GALC gene contains 17 exons spanning about 60 kb of genomic DNA. GALC has a GC-rich promoter region similar to the genes of other lysosomal proteins. </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>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By isotopic in situ hybridization, Cannizzaro et al. (1994) mapped the GALC gene to chromosome 14q31. </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>
|
|
</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<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 (606463), GALC, 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>
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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>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>Sakai et al. (1994) identified homozygosity for a nonsense mutation (E385X; 606890.0001) in a patient with typical Krabbe disease (KRB; 245200). </p><p>Rafi et al. (1995) analyzed the GALC gene in 2 patients with infantile Krabbe disease and identified homozygosity for a 30-kb deletion (606890.0002) that was found to be associated with a 502C-T transition on the same allele, which they designated '502/del.' The transition was determined to be a polymorphism. Expression of the 502/del mutation in COS-1 cells resulted in no measurable GALC activity above that in mock-transfected cells. Rafi et al. (1995) studied an additional 46 patients with infantile Krabbe disease and identified 8 who were homozygous for the 502/del allele and 5 who were compound heterozygotes for the 502/del allele and a second mutant allele, the latter including 3 missense mutations and 1 single nucleotide insertion which had not yet been confirmed by expression studies. The authors noted that 11 patients did not have the 502 polymorphism, but that no patient was found with the deletion who did not carry the 502 polymorphism. </p><p>De Gasperi et al. (1996) analyzed the galactocerebrosidase gene in 9 families with late-onset globoid cell leukoencephalopathy (GLD) and in 1 patient with classic Krabbe disease. They reported that 5 of the patients were compound heterozygotes for the 30-kb deletion (606890.0002) first reported by Rafi et al. (1995) and another mutation in the GALC gene. De Gasperi et al. (1996) identified 6 missense mutations: R63H, G95S, M101L, G268S, Y298C, and I234T. They also identified a nonsense mutation (S7X), a 1-bp deletion mutation (805delG), a mutation that interferes with splicing of intron 1, and a 34-nucleotide insertion in the RNA caused by the aberrant splicing of intron 6. Most of the novel mutations identified appeared to be private family mutations. In an erratum, De Gasperi et al. (1996) stated that the loss of a restriction site in exon 8 of the GALC gene in families 2 and 3 with GLD was not due to the 805delG substitution but to an 809G-A transition resulting in a G270D missense mutation; the 805delG substitution identified in 1 member of family 2 led to loss of the same restriction site but the significance of the change was uncertain. </p><p>In 2 different inbred communities in Israel with Krabbe disease, Rafi et al. (1996) identified 2 different founder mutations in the GALC gene: one in a Moslem Arab population (606890.0003) and one in a Druze population (606890.0004). </p><p>In 4 Japanese patients with adult-onset Krabbe disease, Furuya et al. (1997) identified 4 novel mutations in the GALC gene. </p><p>Xu et al. (2006) investigated mutations of the GALC gene in 17 unrelated Japanese patients with Krabbe disease and reviewed the mutations previously reported in 11 Japanese patients. The authors found that 12del3ins and I66M + I289V, which had been identified only in Japanese individuals to date, accounted for 37% of the mutant alleles; with 2 additional mutations, G270D and T652P, these accounted for up to 57% of mutations in Japanese patients. Xu et al. (2006) observed a tendency for the I66M + I289V, G270D, and L618S mutations to be associated with a mild phenotype. </p><p>Among 30 unrelated Italian patients with Krabbe disease, Tappino et al. (2010) identified 33 different mutations in the GALC gene, including 14 novel mutations (see, e.g., 606890.0005-606890.0009). The 15 novel mutations included 4 missense mutations in highly conserved residues, 7 frameshift mutations, 3 nonsense mutations, and 1 splice site mutation. Thus, 73% of the newly described mutations were expected to affect mRNA processing. In silico analysis predicted that the missense mutations had a high probability of being deleterious. The common 30-kb deletion (606890.0002) accounted for 18% of mutant alleles, and 4 patients had a founder mutation (G553R; 606890.0005). Otherwise, most of the mutations were private. There were no clear genotype-phenotype correlations, but some missense mutations were associated with milder phenotypes (see, e.g., G286D; 606890.0008). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Victoria et al. (1996) found that the disease-causing mutation in the canine GALC gene was demonstrated to be an A-to-C transversion at cDNA position 473 (Y158S). </p><p>Luzi et al. (1997) found that the mutation causing GLD in the rhesus monkey was a deletion of AC corresponding to cDNA positions 387 and 388 in exon 4. This resulted in a frameshift and stop codon after 46 nucleotides. Using an engineered sense primer and an antisense primer from intron 4, Luzi et al. (1997) developed a rapid method to detect the GALC mutation. When 45 monkeys from 1 colony were tested, 22 were found to be carriers. The availability of this nonhuman primate model of GLD provides unique opportunities to evaluate treatment for this severe disease. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>10 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 KRABBE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALC, GLU385TER
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908010,
|
|
|
|
|
|
|
|
ClinVar: RCV000004022
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with typical Krabbe disease (KRB; 245200), Sakai et al. (1994) identified homozygosity for a GAA-to-TAA mutation in codon 385, predicting a glu385-to-ter (E385X) substitution. This mutation, originally reported as GLU369TER, has been renumbered based on the first ATG initiation codon as nucleotide +1 (Tappino et al., 2010). </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 KRABBE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALC, 30-KB DEL, IVS10
|
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|
|
|
<br />
|
|
|
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|
|
ClinVar: RCV000004023
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|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Rafi et al. (1995) analyzed the GALC gene in 2 patients with infantile Krabbe disease and identified homozygosity for a deletion of exons 11-17 that was found to be associated with a 502C-T transition on the same allele, which they designated '502/del.' The transition was later determined to be a polymorphism. Expression of the 502/del mutation in COS-1 cells resulted in no measurable GALC activity above that in mock-transfected cells. Rafi et al. (1995) studied an additional 46 patients with infantile Krabbe disease and identified 8 who were homozygous for the 502/del allele and 5 who were compound heterozygotes for 502/del allele and a second mutant allele. There were 21 patients who were heterozygous and 1 who was homozygous for the 502 polymorphism in whom the presence of the deletion could not be confirmed, but no patient was found with the deletion who did not carry the 502 polymorphism. Luzi et al. (1995) determined that the deletion is approximately 30 kb starting near the middle of intron 10 and including all of the coding region through exon 17 plus an additional 9 kb. </p><p>De Gasperi et al. (1996) analyzed the GALC gene in 9 families with late-onset globoid cell leukoencephalopathy and in 1 patient with classic Krabbe disease and found that 5 of the patients were compound heterozygotes for the 30-kb deletion first reported by Rafi et al. (1995) and another mutation in the GALC gene. </p><p>Kleijer et al. (1997) found that the 30-kb deletion was present in 52% of mutant alleles from 41 Dutch patients with Krabbe disease. </p><p>Tappino et al. (2010) found the 30-kb deletion in 18% of disease alleles among their cohort of 30 Italian patients. They stated that the 502C-T transition has been renumbered as 550C-T based on the first ATG initiation codon as nucleotide +1. </p>
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|
</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>.0003 KRABBE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
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<span class="mim-text-font">
|
|
|
|
GALC, ASP544ASN
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|
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|
|
<br />
|
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|
|
SNP: rs387906952,
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|
|
gnomAD: rs387906952,
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|
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ClinVar: RCV000023588, RCV001270016
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from an inbred Arab Israeli population with infantile Krabbe disease (KRB; 245200), Rafi et al. (1996) identified a homozygous 1630G-A transition in exon 14 of the GALC gene, resulting in an asp544-to-asn (D544N) substitution in the 30-kD subunit. The findings were consistent with a founder effect. In vitro functional expression studies showed that the mutant protein had no enzymatic activity. This mutation, originally reported as ASP528ASN, has been renumbered based on the first ATG initiation codon as nucleotide +1 (Tappino et al., 2010). </p>
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|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 KRABBE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALC, ILE599SER
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|
|
|
|
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<br />
|
|
|
|
SNP: rs387906953,
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|
|
|
|
|
|
|
ClinVar: RCV000023589
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|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from an inbred Druze population in northern Israel with infantile Krabbe disease (KRB; 245200), Rafi et al. (1996) identified a homozygous 1796T-G transversion in exon 15 of the GALC gene, resulting in an ile599-to-ser (I599S) substitution in the 30-kD subunit. The findings were consistent with a founder effect. In vitro functional expression studies showed that the mutant protein had no enzymatic activity. This mutation, originally reported as ILE583SER, has been renumbered based on the first ATG initiation codon as nucleotide +1 (Tappino et al., 2010). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 KRABBE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
GALC, GLY553ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs748573754,
|
|
|
|
|
|
gnomAD: rs748573754,
|
|
|
|
|
|
ClinVar: RCV000169525, RCV003137698
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with Krabbe disease (KRB; 245200), Tappino et al. (2010) identified a 1657G-A transition in exon 14 of the GALC gene, resulting in a gly553-to-arg (G553R) substitution. The G553R mutation was found in 7 Italian patients from southern Italy, and haplotype analysis indicated a founder effect. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<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 KRABBE DISEASE</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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GALC, IVS13DS, G-A, +1
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<br />
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SNP: rs2139956292,
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ClinVar: RCV000023591
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In an Italian patient with classic Krabbe disease (KRB; 245200), Tappino et al. (2010) identified compound heterozygosity for 2 mutations in the GALC gene: a G-to-A transition (1489+1G-A) in intron 13, demonstrated to cause partial skipping of exon 13 and premature termination, and a 1-bp deletion (1901delT; 606890.0007), also predicted to result in premature termination. The patient presented at age 5 months with truncal hypotonia, hypertonia, spasticity, and white matter changes. Residual GALC activity was 9.7% of control levels. </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 KRABBE DISEASE</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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GALC, 1-BP DEL, 1901T
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<br />
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SNP: rs1555378534,
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ClinVar: RCV000670467
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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>For discussion of the 1-bp deletion (1901delT) in the GALC gene that was identified in compound heterozygous state in a patient with Krabbe disease (KRB; 245200) by Tappino et al. (2010), see 606890.0006. </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 KRABBE DISEASE</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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GALC, GLY286ASP
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<br />
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SNP: rs199847983,
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gnomAD: rs199847983,
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ClinVar: RCV000023593, RCV000363446
|
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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 an Italian patient with juvenile onset of Krabbe disease (KRB; 245200) at age 4 years, Tappino et al. (2010) identified compound heterozygosity for 2 mutations in the GALC gene: an 857G-A transition in exon 8, resulting in a gly286-to-asp (G286D) substitution in a highly conserved residue, and the common 30-kb deletion (606890.0002). An unrelated patient with onset of Krabbe disease at age 26 was compound heterozygous for the G286D mutation and a 953C-G transversion in exon 9, resulting in a pro318-to-arg (P318R; 606890.0009) substitution in a highly conserved residue. Tappino et al. (2010) speculated that the G286D mutation may be a mild lesion resulting in a less severe phenotype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0009 KRABBE DISEASE</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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GALC, PRO318ARG
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<br />
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SNP: rs387906954,
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gnomAD: rs387906954,
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ClinVar: RCV000023594
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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>See 606890.0008 and Tappino et al. (2010) </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0010 KRABBE DISEASE</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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GALC, GLY41SER
|
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<br />
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SNP: rs387906955,
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gnomAD: rs387906955,
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ClinVar: RCV000023595
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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>Fiumara et al. (2011) identified a 121G-A transition in the GALC gene, resulting in a gly41-to-ser (G41S) substitution, as a founder mutation for Krabbe disease (KRB; 245200) among Sicilian Italians from the region of Catania. The mutation was enriched among 17 patients with onset of disease after age 6 months. Among the 4 patients who were homozygous for the mutation, enzyme activity ranged between 1 and 6% of controls, but there was no correlation between enzyme activity and age at onset or disease course. However, Fiumara et al. (2011) concluded that the G41S mutation is associated with a protracted course of the disorder, although patients were significantly disabled. </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">
|
|
Duchen et al. (1980); Kodama et al. (1982); Lyerla et al. (1989);
|
|
Rushton and Dawson (1977); Sweet (1986); Zlotogora et al. (1990);
|
|
Zlotogora et al. (1985)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
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<ol>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Cannizzaro, L. A., Chen, Y. Q., Rafi, M. A., Wenger, D. A.
|
|
<strong>Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 66: 244-245, 1994.
|
|
|
|
|
|
[PubMed: 8162701]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000133703]
|
|
|
|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, Y. Q., Rafi, M. A., de Gala, G., Wenger, D. A.
|
|
<strong>Cloning and expression of cDNA encoding human galactocerebrosidase, the enzyme deficient in globoid cell leukodystrophy.</strong>
|
|
Hum. Molec. Genet. 2: 1841-1845, 1993.
|
|
|
|
|
|
[PubMed: 8281145]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.11.1841]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, Y. Q., Wenger, D. A.
|
|
<strong>Galactocerebrosidase from human urine: purification and partial characterization.</strong>
|
|
Biochim. Biophys. Acta 1170: 53-61, 1993.
|
|
|
|
|
|
[PubMed: 8399327]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0005-2760(93)90175-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Gasperi, R., Gama Sosa, M. A., Sartorato, E. L., Battistini, S., MacFarlane, H., Gusella, J. F., Krivit, W., Kolodny, E. H.
|
|
<strong>Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy.</strong>
|
|
Am. J. Hum. Genet. 59: 1233-1242, 1996. Note: Erratum: Am. J. Hum. Genet. 60: 1264 only, 1997.
|
|
|
|
|
|
[PubMed: 8940268]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Duchen, L. W., Eicher, E. M., Jacobs, J. M., Scaravilli, F., Teixeira, F.
|
|
<strong>Hereditary leucodystrophy in the mouse: the new mutant twitcher.</strong>
|
|
Brain 103: 695-710, 1980.
|
|
|
|
|
|
[PubMed: 7417782]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/103.3.695]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fiumara, A., Barone, R., Arena, A., Filocamo, M., Lissens, W., Pavone, L., Sorge, G.
|
|
<strong>Krabbe leukodystrophy in a selected population with high rate of late onset forms: longer survival linked to c.121G-A (p.gly41ser) mutation.</strong>
|
|
Clin. Genet. 80: 452-458, 2011.
|
|
|
|
|
|
[PubMed: 21070211]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2010.01572.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Furuya, H., Kukita, Y., Nagano, S., Sakai, Y., Yamashita, Y., Fukuyama, H., Inatomi, Y., Saito, Y., Koike, R., Tsuji, S., Fukumaki, Y., Hayashi, K., Kobayashi, T.
|
|
<strong>Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients.</strong>
|
|
Hum. Genet. 100: 450-456, 1997.
|
|
|
|
|
|
[PubMed: 9272171]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050532]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kleijer, W. J., Keulemans, J. L. M., van der Kraan, M., Geilen, G. G., van der Helm, R. M., Rafi, M. A., Luzi, P., Wenger, D. A., Halley, D. J. J., van Diggelen, O. P.
|
|
<strong>Prevalent mutations in the GALC gene of patients with Krabbe disease of Dutch and other European origin.</strong>
|
|
J. Inherit. Metab. Dis. 20: 587-594, 1997.
|
|
|
|
|
|
[PubMed: 9266397]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1023/a:1005315311165]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
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: 26095250]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2015.05.051]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kodama, S., Igisu, H., Siegel, D. A., Suzuki, K.
|
|
<strong>Glycosylceramide synthesis in the developing spinal cord and kidney of the twitcher mouse, an enzymatically authentic model of human Krabbe disease.</strong>
|
|
J. Neurochem. 39: 1314-1318, 1982.
|
|
|
|
|
|
[PubMed: 6811701]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1471-4159.1982.tb12572.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Luzi, P., Rafi, M. A., Victoria, T., Baskin, G. B., Wenger, D. A.
|
|
<strong>Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate.</strong>
|
|
Genomics 42: 319-324, 1997.
|
|
|
|
|
|
[PubMed: 9192853]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1997.4744]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Luzi, P., Rafi, M. A., Wenger, D. A.
|
|
<strong>Characterization of the large deletion in the GALC gene found in patients with Krabbe disease.</strong>
|
|
Hum. Molec. Genet. 4: 2335-2338, 1995.
|
|
|
|
|
|
[PubMed: 8634707]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.12.2335]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Luzi, P., Rafi, M. A., Wenger, D. A.
|
|
<strong>Structure and organization of the human galactocerebrosidase (GALC) gene.</strong>
|
|
Genomics 26: 407-409, 1995.
|
|
|
|
|
|
[PubMed: 7601472]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(95)80230-j]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lyerla, T. A., Konola, J. T., Skiba, M. C., Raghavan, S.
|
|
<strong>Galactocerebrosidase activity in somatic cell hybrids derived from twitcher mouse/control human fibroblasts is associated with human chromosome 17.</strong>
|
|
Am. J. Hum. Genet. 44: 198-207, 1989.
|
|
|
|
|
|
[PubMed: 2912067]
|
|
|
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|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rafi, M. A., Luzi, P., Chen, Y. Q., Wenger, D. A.
|
|
<strong>A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease.</strong>
|
|
Hum. Molec. Genet. 4: 1285-1289, 1995.
|
|
|
|
|
|
[PubMed: 7581365]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.8.1285]
|
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rafi, M. A., Luzi, P., Zlotogora, J., Wenger, D. A.
|
|
<strong>Two different mutations are responsible for Krabbe disease in the Druze and Moslem Arab populations in Israel.</strong>
|
|
Hum. Genet. 97: 304-308, 1996.
|
|
|
|
|
|
[PubMed: 8786069]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF02185759]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rushton, A. R., Dawson, G.
|
|
<strong>Genetic linkage studies of the human glycosphingolipid beta-galactosidases.</strong>
|
|
Biochem. Genet. 15: 1071-1082, 1977.
|
|
|
|
|
|
[PubMed: 414740]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00484498]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sakai, N., Inui, K., Fujii, N., Fukushima, H., Nishimoto, J., Yanagihara, I., Isegawa, Y., Iwamatsu, A., Okada, S.
|
|
<strong>Krabbe disease: isolation and characterization of a full-length cDNA for human galactocerebrosidase.</strong>
|
|
Biochem. Biophys. Res. Commun. 198: 485-491, 1994.
|
|
|
|
|
|
[PubMed: 8297359]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1994.1071]
|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sweet, H.
|
|
<strong>Twitcher (twi) is on chromosome 12.</strong>
|
|
Mouse Newsletter 75: 30, 1986.
|
|
|
|
</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Tappino, B., Biancheri, R., Mort, M., Regis, S., Corsolini, F., Rossi, A., Stroppiano, M., Lualdi, S., Fiumara, A., Bembi, B., Di Rocco, M., Cooper, D. N., Filocamo, M.
|
|
<strong>Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.</strong>
|
|
Hum. Mutat. 31: E1894-1914, 2010. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 20886637]
|
|
|
|
|
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[Full Text: https://doi.org/10.1002/humu.21367]
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Victoria, T., Rafi, M. A., Wenger, D. A.
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<strong>Cloning of the canine GALC cDNA and identification of the mutation causing globoid cell leukodystrophy in West Highland White and Cairn terriers.</strong>
|
|
Genomics 33: 457-462, 1996.
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[PubMed: 8661004]
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[Full Text: https://doi.org/10.1006/geno.1996.0220]
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Xu, C., Sakai, N., Taniike, M., Inui, K., Ozono, K.
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<strong>Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation.</strong>
|
|
J. Hum. Genet. 51: 548-554, 2006.
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[PubMed: 16607461]
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[Full Text: https://doi.org/10.1007/s10038-006-0396-3]
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Zlotogora, J., Chakraborty, S., Knowlton, R. G., Wenger, D. A.
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<strong>Krabbe disease locus mapped to chromosome 14 by genetic linkage.</strong>
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Am. J. Hum. Genet. 47: 37-44, 1990.
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[PubMed: 1971996]
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Zlotogora, J., Regev, R., Zeigler, M., Iancu, T. C., Bach, G.
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<strong>Krabbe disease: increased incidence in a highly inbred community.</strong>
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Am. J. Med. Genet. 21: 765-770, 1985.
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[PubMed: 4025402]
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[Full Text: https://doi.org/10.1002/ajmg.1320210420]
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Paul J. Converse - updated : 02/05/2016<br>Cassandra L. Kniffin - updated : 10/27/2011<br>Marla J. F. O'Neill - updated : 12/12/2006
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