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Entry
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- *613497 - LIPASE A, LYSOSOMAL ACID; LIPA
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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">*613497</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</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="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/613497">Table View</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<div 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=ENSG00000107798;t=ENST00000336233" 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=3988" 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=613497" 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 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=ENSG00000107798;t=ENST00000336233" 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_000235,NM_001127605,NM_001288979,XM_024448023" 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_000235" 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=613497" 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://www.proteinatlas.org/search/LIPA" 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/187152,434306,460143,505053,506431,544575,15126727,34531203,51317399,62897079,68067636,119570525,119570526,119570527,158261505,189054449,189083851,193787174,193788387,194373765,194386064,572876118,1370457145,2462519347" 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/P38571" 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 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=3988" 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=ENSG00000107798;t=ENST00000336233" 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=LIPA" 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=LIPA" 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+3988" 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/LIPA" 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:3988" 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/3988" 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=chr10&hgg_gene=ENST00000336233.10&hgg_start=89213572&hgg_end=89251775&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:6617" 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:6617" 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/lipa" 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=613497[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=613497[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000107798" 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=LIPA" 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=LIPA" 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=LIPA" 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=LIPA&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/PA30391" 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:6617" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0023495.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:96789" 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/LIPA#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:96789" 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/3988/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=3988" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00008510;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00008510 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00009773;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00009773 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00010062;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00010062 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00019376;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00019376 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00020016;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00020016 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00021963;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00021963 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00022642;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00022642 </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 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:3988" 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=LIPA&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> 57218003, 82500001<br />
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<strong>ICD10CM:</strong> E75.5<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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613497
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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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LIPASE A, LYSOSOMAL ACID; LIPA
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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LYSOSOMAL ACID LIPASE; LAL<br />
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CHOLESTEROL ESTER HYDROLASE
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=LIPA" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">LIPA</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/10/379?start=-3&limit=10&highlight=379">10q23.31</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:89213572-89251775&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'})">10:89,213,572-89,251,775</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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|
Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=278000,620151" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
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</th>
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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>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/10/379?start=-3&limit=10&highlight=379">
|
|
10q23.31
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Cholesteryl ester storage 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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<a href="/entry/278000"> 278000 </a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p><a href="#3" class="mim-tip-reference" title="Anderson, R. A., Sando, G. N. <strong>Cloning and expression of cDNA encoding human lysosomal acid lipase/cholesteryl ester hydrolase: similarities to gastric and lingual lipases.</strong> J. Biol. Chem. 266: 22479-22484, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1718995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1718995</a>]" pmid="1718995">Anderson and Sando (1991)</a> reported that the amino acid sequence of lysosomal acid lipase (LAL; cholesteryl ester hydrolase; <a href="https://enzyme.expasy.org/EC/3.1.1.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 3.1.1.13</a>) as deduced from the 2.6-kb cDNA nucleotide sequence is 58% identical to that of human gastric lipase (LIPF; <a href="/entry/601980">601980</a>), which is involved in the preduodenal breakdown of ingested triglycerides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1718995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#1" class="mim-tip-reference" title="Anderson, R. A., Byrum, R. S., Coates, P. M., Sando, G. N. <strong>Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease.</strong> Proc. Nat. Acad. Sci. 91: 2718-2722, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8146180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8146180</a>] [<a href="https://doi.org/10.1073/pnas.91.7.2718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8146180">Anderson et al. (1994)</a> isolated and sequenced the gene for LIPA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8146180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The distinct kinetic and physical properties of lipases A and B (LIPB; <a href="/entry/247980">247980</a>) were defined by <a href="#17" class="mim-tip-reference" title="Warner, T. G., Dambach, L. M., Shin, J. H., O'Brien, J. S. <strong>Separation and characterization of the acid lipase and neutral esterases from human liver.</strong> Am. J. Hum. Genet. 32: 869-879, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7446527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7446527</a>]" pmid="7446527">Warner et al. (1980)</a>. They stated that the natural substrate for LIPB was not known, and that it was not clear that LIPB is a lysosomal hydrolase. LIPA may serve an important role in cellular metabolism by releasing cholesterol. The liberated cholesterol suppresses further cholesterol synthesis and stimulates esterification of cholesterol within the cell. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7446527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#4" class="mim-tip-reference" title="Aslanidis, C., Klima, H., Lackner, K. J., Schmitz, G. <strong>Genomic organization of the human lysosomal acid lipase gene (LIPA).</strong> Genomics 20: 329-331, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8020990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8020990</a>] [<a href="https://doi.org/10.1006/geno.1994.1180" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8020990">Aslanidis et al. (1994)</a> summarized the exon structure of the LIPA gene, which consists of 10 exons, together with the sizes of genomic EcoRI and SacI fragments hybridizing to each exon. The DNA sequence of the putative promoter region was presented. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8020990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#1" class="mim-tip-reference" title="Anderson, R. A., Byrum, R. S., Coates, P. M., Sando, G. N. <strong>Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease.</strong> Proc. Nat. Acad. Sci. 91: 2718-2722, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8146180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8146180</a>] [<a href="https://doi.org/10.1073/pnas.91.7.2718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8146180">Anderson et al. (1994)</a> found that the LIPA gene is spread over 36 kb of genomic DNA. The 5-prime flanking region is GC-rich and has characteristics of a 'housekeeping' gene promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8146180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Koch et al. (<a href="#9" class="mim-tip-reference" title="Koch, G. A., McAvoy, M., Naylor, S. L., Byers, M. G., Haley, L. L., Eddy, R. L., Brown, J. A., Shows, T. B. <strong>Assignment of lipase A (LIPA) to human chromosome 10. (Abstract)</strong> Cytogenet. Cell Genet. 25: 174, 1979."None>1979</a>, <a href="#10" class="mim-tip-reference" title="Koch, G., Lalley, P. A., McAvoy, M., Shows, T. B. <strong>Assignment of LIPA, associated with human acid lipase deficiency to human chromosome 10 and comparative assignment to mouse chromosome 19.</strong> Somat. Cell Genet. 7: 345-358, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7292252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7292252</a>] [<a href="https://doi.org/10.1007/BF01538859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7292252">1981</a>) assigned lysosomal acid lipase A to chromosome 10 by human-Chinese hamster somatic cell hybrids. Judging from the close concordance with soluble glutamate oxaloacetate transaminase (GOT1; <a href="/entry/138180">138180</a>), these loci were thought to be close together on the long arm of 10. Lipase A is encoded by chromosome 19 in mouse (<a href="#10" class="mim-tip-reference" title="Koch, G., Lalley, P. A., McAvoy, M., Shows, T. B. <strong>Assignment of LIPA, associated with human acid lipase deficiency to human chromosome 10 and comparative assignment to mouse chromosome 19.</strong> Somat. Cell Genet. 7: 345-358, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7292252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7292252</a>] [<a href="https://doi.org/10.1007/BF01538859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7292252">Koch et al., 1981</a>). GOT1 is also on chromosome 10q in man and 19 in mouse. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7292252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By fluorescence in situ hybridization, <a href="#2" class="mim-tip-reference" title="Anderson, R. A., Rao, N., Byrum, R. S., Rothschild, C. B., Bowden, D. W., Hayworth, R., Pettenati, M. <strong>In situ localization of the genetic locus encoding the lysosomal acid lipase/cholesteryl esterase (LIPA) deficient in Wolman disease to chromosome 10q23.2-q23.3.</strong> Genomics 15: 245-247, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432549</a>] [<a href="https://doi.org/10.1006/geno.1993.1052" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432549">Anderson et al. (1993)</a> mapped the LIPA locus to 10q23.2-q.23.3. It was clearly distinct from the locus for pancreatic lipase (<a href="/entry/246600">246600</a>) at 10q26.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Cholesteryl ester storage disease (CESD; <a href="/entry/278000">278000</a>) and Wolman disease (WOLD; <a href="/entry/620151">620151</a>) are autosomal recessive allelic disorders associated with reduced activity and genetic defects of lysosomal acid lipase. <a href="#5" class="mim-tip-reference" title="Aslanidis, C., Ries, S., Fehringer, P., Buchler, C., Klima, H., Schmitz, G. <strong>Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.</strong> Genomics 33: 85-93, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8617513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8617513</a>] [<a href="https://doi.org/10.1006/geno.1996.0162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8617513">Aslanidis et al. (1996)</a> provided evidence that the strikingly more severe course of Wolman disease is caused by genetic defects of LAL that leave no residual enzyme activity. In a CESD patient, a G-to-A transition at position -1 of the exon 8 splice donor site (<a href="#0002">613497.0002</a>) resulted in skipping of exon 8 in 97% of the mRNA originating from this allele, while 3% was spliced correctly, resulting in full-length LAL enzyme. Two sibs with Wolman disease were homozygous for a splice site mutation involving the same donor site but permitting no correct splicing or subsequent synthesis of functional enzyme (<a href="#0004">613497.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8617513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Pagani, F., Garcia, R., Pariyarath, R., Stuani, C., Gridelli, B., Paone, G., Baralle, F. E. <strong>Expression of lysosomal acid lipase mutants detected in three patients with cholesteryl ester storage disease.</strong> Hum. Molec. Genet. 5: 1611-1617, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8894696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8894696</a>] [<a href="https://doi.org/10.1093/hmg/5.10.1611" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8894696">Pagani et al. (1996)</a> described the molecular basis of CESD in 3 patients. They identified mutations by sequence analysis of LAL cDNA and genomic DNA. The role of the mutations as the direct cause of the disease was confirmed by measuring the LAL enzymatic activity of extracts from cells transfected with LAL mutants. The 3 CESD patients were found to be compound heterozygotes. <a href="#16" class="mim-tip-reference" title="Pagani, F., Garcia, R., Pariyarath, R., Stuani, C., Gridelli, B., Paone, G., Baralle, F. E. <strong>Expression of lysosomal acid lipase mutants detected in three patients with cholesteryl ester storage disease.</strong> Hum. Molec. Genet. 5: 1611-1617, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8894696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8894696</a>] [<a href="https://doi.org/10.1093/hmg/5.10.1611" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8894696">Pagani et al. (1996)</a> identified 3 different missense mutations, 2 splicing defects, and a null allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8894696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an Azerbaijani girl, born to consanguineous parents, with CESD, <a href="#6" class="mim-tip-reference" title="Bychkov, I. O., Kamenets, E. A., Filatova, A. Y., Skoblov, M. Y., Mikhaylova, S. V., Strokova, T. V., Gundobina, O. S., Zakharova, E. Y. <strong>The novel synonymous variant in LIPA gene affects splicing and causes lysosomal acid lipase deficiency.</strong> Molec. Genet. Metab. 127: 212-215, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31230978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31230978</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.06.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31230978">Bychkov et al. (2019)</a> identified homozygosity for a synonymous mutation in the LIPS gene (<a href="#0008">613497.0008</a>) that was predicted to result in abnormal splicing. Analysis of patient mRNA showed a deletion of 63-bp in exon 6 of the LIPA transcript, corresponding to activation of a cryptic splice site. The parents were found to be heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31230978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="/allelicVariants/613497" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=613497[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 WOLMAN DISEASE</strong>
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CHOLESTERYL ESTER STORAGE DISEASE, INCLUDED
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LIPA, LEU179PRO
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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> rs121965086 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965086;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/rs121965086?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=rs121965086" 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=rs121965086" 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=RCV000000095 OR RCV000000096" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000095, RCV000000096" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000095...</a>
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<p><strong><em>Wolman Disease</em></strong></p><p>
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In a proband with Wolman disease (WOLD; <a href="/entry/620151">620151</a>) from a nonconsanguineous family, <a href="#1" class="mim-tip-reference" title="Anderson, R. A., Byrum, R. S., Coates, P. M., Sando, G. N. <strong>Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease.</strong> Proc. Nat. Acad. Sci. 91: 2718-2722, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8146180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8146180</a>] [<a href="https://doi.org/10.1073/pnas.91.7.2718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8146180">Anderson et al. (1994)</a> detected a T-to-C transition at nucleotide 639 of the LIPA gene that resulted in a nonconservative missense mutation, leu179 to pro (L179P). This mutation was found in compound heterozygosity with a single-base insertion resulting in a null allele (<a href="#0004">613497.0004</a>). The proband had had 2 older sibs with Wolman disease. <a href="#1" class="mim-tip-reference" title="Anderson, R. A., Byrum, R. S., Coates, P. M., Sando, G. N. <strong>Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease.</strong> Proc. Nat. Acad. Sci. 91: 2718-2722, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8146180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8146180</a>] [<a href="https://doi.org/10.1073/pnas.91.7.2718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8146180">Anderson et al. (1994)</a> noted that the L179P mutation is located 26 amino acids from the predicted active site of lysosomal acid lipase and was expected to disrupt the alpha-helical structure in a highly conserved region of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8146180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Cholesteryl Ester Storage Disease</em></strong></p><p>
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<a href="#13" class="mim-tip-reference" title="Maslen, C. L., Illingworth, D. R. <strong>Molecular genetics of cholesterol ester hydrolase deficiency. (Abstract)</strong> Am. J. Hum. Genet. 53 (suppl.): A926, 1993."None>Maslen and Illingworth (1993)</a> and <a href="#12" class="mim-tip-reference" title="Maslen, C. L., Babcock, D., Illingworth, D. R. <strong>Occurrence of a mutation associated with Wolman disease in a family with cholesteryl ester storage disease.</strong> J. Inherit. Metab. Dis. 18: 620-623, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8598644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8598644</a>] [<a href="https://doi.org/10.1007/BF02436008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8598644">Maslen et al. (1995)</a> found the L179P mutation in 2 sibs with cholesteryl ester storage disease (CESD; <a href="/entry/278000">278000</a>). In these sibs the L179P mutation, inherited from the mother, was found in compound heterozygosity with a splice site mutation that resulted in skipping of exon 8 of lysosomal acid lipase (<a href="#0002">613497.0002</a>). <a href="#12" class="mim-tip-reference" title="Maslen, C. L., Babcock, D., Illingworth, D. R. <strong>Occurrence of a mutation associated with Wolman disease in a family with cholesteryl ester storage disease.</strong> J. Inherit. Metab. Dis. 18: 620-623, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8598644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8598644</a>] [<a href="https://doi.org/10.1007/BF02436008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8598644">Maslen et al. (1995)</a> compared the phenotypes of other patients carrying the L179P or the splice site mutation described by them and concluded that the L179P mutant allele apparently does not make a substantial contribution to cholesteryl ester hydrolase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8598644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CHOLESTERYL ESTER STORAGE DISEASE</strong>
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LIPA, 934G-A
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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> rs116928232 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs116928232;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/rs116928232?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=rs116928232" 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=rs116928232" 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=RCV000185528 OR RCV000478829 OR RCV000778291 OR RCV001376623 OR RCV001823874 OR RCV002372140 OR RCV005003537" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000185528, RCV000478829, RCV000778291, RCV001376623, RCV001823874, RCV002372140, RCV005003537" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000185528...</a>
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<p>In a 12-year-old patient with cholesteryl ester storage disease (CESD; <a href="/entry/278000">278000</a>) from a nonconsanguineous Polish-German family, <a href="#8" class="mim-tip-reference" title="Klima, H., Ullrich, K., Aslanidis, C., Fehringer, P., Lackner, K. J., Schmitz, G. <strong>A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.</strong> J. Clin. Invest. 92: 2713-2718, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8254026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8254026</a>] [<a href="https://doi.org/10.1172/JCI116888" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8254026">Klima et al. (1993)</a> detected a 72-bp in-frame deletion resulting in the loss of amino acid codons 254 through 277. Analysis of genomic DNA revealed that the 72 bp represented an exon, indicating that the deletion in the mRNA was caused by defective splicing. Sequence analysis of the patient's genomic DNA revealed a G-to-A substitution in the last nucleotide of the 72-bp exon on 1 allele. No normal-sized mRNA was detectable in the propositus even though he was not homozygous for the splice site mutation. <a href="#8" class="mim-tip-reference" title="Klima, H., Ullrich, K., Aslanidis, C., Fehringer, P., Lackner, K. J., Schmitz, G. <strong>A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.</strong> J. Clin. Invest. 92: 2713-2718, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8254026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8254026</a>] [<a href="https://doi.org/10.1172/JCI116888" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8254026">Klima et al. (1993)</a> concluded that the patient was compound heterozygous for the splice site mutation and a null allele. The patient showed LIPA activity in cultured skin fibroblasts approximately 9% of normal. Hepatosplenomegaly had been present since age 5 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8254026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#5" class="mim-tip-reference" title="Aslanidis, C., Ries, S., Fehringer, P., Buchler, C., Klima, H., Schmitz, G. <strong>Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.</strong> Genomics 33: 85-93, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8617513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8617513</a>] [<a href="https://doi.org/10.1006/geno.1996.0162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8617513">Aslanidis et al. (1996)</a> restudied the patient of <a href="#8" class="mim-tip-reference" title="Klima, H., Ullrich, K., Aslanidis, C., Fehringer, P., Lackner, K. J., Schmitz, G. <strong>A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.</strong> J. Clin. Invest. 92: 2713-2718, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8254026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8254026</a>] [<a href="https://doi.org/10.1172/JCI116888" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8254026">Klima et al. (1993)</a> and defined the splice site mutation as a G-to-A mutation at position -1 of the splice donor site following exon 8, resulting in incorrect splicing and the removal of the 72-bp exon 8 of the LIPA gene. They determined that the other allele of the patient carried a premature termination mutation (<a href="#0003">613497.0003</a>) as well as the L179P mutation (<a href="#0001">613497.0001</a>); the LIPA mRNA was rendered unstable by the premature stop codon. <a href="#5" class="mim-tip-reference" title="Aslanidis, C., Ries, S., Fehringer, P., Buchler, C., Klima, H., Schmitz, G. <strong>Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.</strong> Genomics 33: 85-93, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8617513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8617513</a>] [<a href="https://doi.org/10.1006/geno.1996.0162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8617513">Aslanidis et al. (1996)</a> demonstrated that the splice site mutation allowed the production of approximately 3 to 4% of correctly spliced mRNA relative to wildtype. <a href="#5" class="mim-tip-reference" title="Aslanidis, C., Ries, S., Fehringer, P., Buchler, C., Klima, H., Schmitz, G. <strong>Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.</strong> Genomics 33: 85-93, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8617513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8617513</a>] [<a href="https://doi.org/10.1006/geno.1996.0162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8617513">Aslanidis et al. (1996)</a> also identified a mutation at the same splice donor site, and also resulting in deletion of exon 8, in 2 sibs with Wolman disease; that mutation, at the +1 position, allowed no correct splicing, and patient fibroblasts were devoid of enzymatic activity. See <a href="#0005">613497.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8617513+8254026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 sibs with CESD, <a href="#13" class="mim-tip-reference" title="Maslen, C. L., Illingworth, D. R. <strong>Molecular genetics of cholesterol ester hydrolase deficiency. (Abstract)</strong> Am. J. Hum. Genet. 53 (suppl.): A926, 1993."None>Maslen and Illingworth (1993)</a> and <a href="#12" class="mim-tip-reference" title="Maslen, C. L., Babcock, D., Illingworth, D. R. <strong>Occurrence of a mutation associated with Wolman disease in a family with cholesteryl ester storage disease.</strong> J. Inherit. Metab. Dis. 18: 620-623, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8598644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8598644</a>] [<a href="https://doi.org/10.1007/BF02436008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8598644">Maslen et al. (1995)</a> identified compound heterozygosity for this splice site mutation in the LIPA gene, inherited from their father, and the L179P mutation (<a href="#0001">613497.0001</a>). The affected children were a sister and brother who presented with idiopathic hepatomegaly at ages 6 and 8 years, respectively. Subsequent analyses indicated that they also had hypercholesterolemia and a severe reduction in cholesteryl ester hydrolase activity in cultured fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8598644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Muntoni, S., Wiebusch, H., Funke, H., Ros, E., Seedorf, U., Assmann, G. <strong>Homozygosity for a splice junction mutation in exon 8 of the gene encoding lysosomal acid lipase in a Spanish kindred with cholesterol ester storage disease (CESD).</strong> Hum. Genet. 95: 491-494, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7759067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7759067</a>] [<a href="https://doi.org/10.1007/BF00223858" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7759067">Muntoni et al. (1995)</a> observed homozygosity for the splice site mutation (<a href="#8" class="mim-tip-reference" title="Klima, H., Ullrich, K., Aslanidis, C., Fehringer, P., Lackner, K. J., Schmitz, G. <strong>A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.</strong> J. Clin. Invest. 92: 2713-2718, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8254026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8254026</a>] [<a href="https://doi.org/10.1172/JCI116888" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8254026">Klima et al., 1993</a>) in a Spanish kindred with cholesterol ester storage disease. Exon 8 of the LIPA gene was deleted. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8254026+7759067" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CHOLESTERYL ESTER STORAGE DISEASE</strong>
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LIPA, GLY245TER
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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> rs267607218 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607218;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/rs267607218?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=rs267607218" 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=rs267607218" 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=RCV000000097 OR RCV001376562 OR RCV001562238 OR RCV001804146 OR RCV005041960" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000097, RCV001376562, RCV001562238, RCV001804146, RCV005041960" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000097...</a>
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<p><a href="#5" class="mim-tip-reference" title="Aslanidis, C., Ries, S., Fehringer, P., Buchler, C., Klima, H., Schmitz, G. <strong>Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.</strong> Genomics 33: 85-93, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8617513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8617513</a>] [<a href="https://doi.org/10.1006/geno.1996.0162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8617513">Aslanidis et al. (1996)</a> determined that the patient of <a href="#8" class="mim-tip-reference" title="Klima, H., Ullrich, K., Aslanidis, C., Fehringer, P., Lackner, K. J., Schmitz, G. <strong>A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.</strong> J. Clin. Invest. 92: 2713-2718, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8254026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8254026</a>] [<a href="https://doi.org/10.1172/JCI116888" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8254026">Klima et al. (1993)</a> with cholesteryl ester storage disease (CESD; <a href="/entry/278000">278000</a>) was compound heterozygous for a G-to-T transversion at nucleotide 836 in exon 7 of the LIPA gene, resulting in substitution of gly245 with a termination codon (G245X), and a splice site mutation resulting in skipping of exon 8 (<a href="#0002">613497.0002</a>). The allele carrying the G245X mutation also carried the L179P mutation (<a href="#0001">613497.0001</a>). <a href="#5" class="mim-tip-reference" title="Aslanidis, C., Ries, S., Fehringer, P., Buchler, C., Klima, H., Schmitz, G. <strong>Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.</strong> Genomics 33: 85-93, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8617513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8617513</a>] [<a href="https://doi.org/10.1006/geno.1996.0162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8617513">Aslanidis et al. (1996)</a> concluded that although the L179P mutation is believed to abolish the enzymatic activity of the lysosomal acid lipase, it is the G245X mutation, through its production of an unstable mRNA, that was responsible for the low level of transcript (approximately 6% of wildtype) derived from the paternal allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8617513+8254026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLMAN DISEASE</strong>
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CHOLESTERYL ESTER STORAGE DISEASE, INCLUDED
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LIPA, 1-BP INS, 634T
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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> rs780495201 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs780495201;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/rs780495201?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=rs780495201" 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=rs780495201" 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=RCV000000099 OR RCV000000100 OR RCV000524544 OR RCV001549751 OR RCV004734493" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000099, RCV000000100, RCV000524544, RCV001549751, RCV004734493" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000099...</a>
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<p><strong><em>Wolman Disease</em></strong></p><p>
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In a proband with Wolman disease (WOLD; <a href="/entry/620151">620151</a>), <a href="#1" class="mim-tip-reference" title="Anderson, R. A., Byrum, R. S., Coates, P. M., Sando, G. N. <strong>Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease.</strong> Proc. Nat. Acad. Sci. 91: 2718-2722, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8146180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8146180</a>] [<a href="https://doi.org/10.1073/pnas.91.7.2718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8146180">Anderson et al. (1994)</a> found compound heterozygosity for insertion of a T nucleotide after nucleotide 634 in exon 6 of the LIPA gene, and a substitution of proline at leucine-179 (<a href="#0001">613497.0001</a>). The 634T insertion occurred at the end of a run of 6 Ts and led to premature termination 12 amino acids downstream. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8146180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Cholesteryl Ester Storage Disease</em></strong></p><p>
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<a href="#1" class="mim-tip-reference" title="Anderson, R. A., Byrum, R. S., Coates, P. M., Sando, G. N. <strong>Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease.</strong> Proc. Nat. Acad. Sci. 91: 2718-2722, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8146180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8146180</a>] [<a href="https://doi.org/10.1073/pnas.91.7.2718" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8146180">Anderson et al. (1994)</a> also found this mutation in a proband and parent from 1 of 11 unrelated families with cholesteryl ester storage disease (CESD; <a href="/entry/278000">278000</a>) examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8146180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1564751995 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1564751995;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=rs1564751995" 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=rs1564751995" 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=RCV000000101" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000101" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000101</a>
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<p>In 2 sibs with Wolman disease (WOLD; <a href="/entry/620151">620151</a>) from a consanguineous family, <a href="#5" class="mim-tip-reference" title="Aslanidis, C., Ries, S., Fehringer, P., Buchler, C., Klima, H., Schmitz, G. <strong>Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.</strong> Genomics 33: 85-93, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8617513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8617513</a>] [<a href="https://doi.org/10.1006/geno.1996.0162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8617513">Aslanidis et al. (1996)</a> detected homozygosity for a G-to-A mutation at position +1 of the splice donor site following exon 8 of the LIPA gene. Both children died within the first year of life. The parents, who were heterozygous for the mutation, had reduced enzymatic activity, while no enzymatic activity was detectable in fibroblasts from the affected children. Although the same donor splice site is involved in the mutation reported in CESD (934G-A, <a href="#0002">613497.0002</a>), the nucleotide at position +1 was changed in the Wolman disease mutation whereas the nucleotide at position -1 was changed in the CESD mutation. Both mutations result in deletion of the same 24 amino acids (exon 8), but the effects are dramatically different: the -1 mutation allowed some correct splicing (3% of total LIPA RNA), but the +1 splice site mutation, which affects one of the invariable nucleotides of the splice consensus sequences, permits no correct splicing. <a href="#5" class="mim-tip-reference" title="Aslanidis, C., Ries, S., Fehringer, P., Buchler, C., Klima, H., Schmitz, G. <strong>Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.</strong> Genomics 33: 85-93, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8617513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8617513</a>] [<a href="https://doi.org/10.1006/geno.1996.0162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8617513">Aslanidis et al. (1996)</a> suggested that the residual activity in CESD patients compared to Wolman patients may result either from a partially active enzyme with the internal deletion of 24 amino acids (skipping of exon 8) or from the production of low amounts of the full size of the protein due to inefficient exon exclusion from the mutated allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8617513" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<strong>.0006 WOLMAN DISEASE</strong>
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LIPA, TYR22TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121965087 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965087;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=rs121965087" 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=rs121965087" 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=RCV000000102" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000102" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000102</a>
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<p>In a Japanese patient with Wolman disease (WOLD; <a href="/entry/620151">620151</a>), <a href="#7" class="mim-tip-reference" title="Fujiyama, J., Sakuraba, H., Kuriyama, M., Fujita, T., Nagata, K., Nakagawa, H., Osame, M. <strong>A new mutation (LIPA Tyr22X) of lysosomal acid lipase gene in a Japanese patient with Wolman disease.</strong> Hum. Mutat. 8: 377-380, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8956047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8956047</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)8:4<377::AID-HUMU15>3.0.CO;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8956047">Fujiyama et al. (1996)</a> identified a tyr22-to-ter (Y22X) mutation of the LIPA gene. The female patient had an umbilical cord herniation at birth. At about 30 days after birth, she showed abdominal distention with hepatosplenomegaly and frequent episodes of diarrhea and vomiting. Abdominal computed tomography revealed massive hepatosplenomegaly and enlargement of the adrenal glands with calcification. Anemia and hepatic failure progressed rapidly and she died at age 114 days. The parents were first cousins. An older sister had died with similar symptoms 80 days after birth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8956047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLMAN 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> rs762559980 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs762559980;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/rs762559980?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=rs762559980" 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=rs762559980" 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=RCV000029177 OR RCV000667513" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000029177, RCV000667513" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000029177...</a>
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<p>In an infant, born of unrelated parents, with Wolman disease (WOLD; <a href="/entry/620151">620151</a>), <a href="#11" class="mim-tip-reference" title="Lee, T. M., Welsh, M., Benhamed, S., Chung, W. K. <strong>Intragenic deletion as a novel type of mutation in Wolman disease.</strong> Molec. Genet. Metab. 104: 703-705, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21963785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21963785</a>] [<a href="https://doi.org/10.1016/j.ymgme.2011.09.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21963785">Lee et al. (2011)</a> identified compound heterozygous mutations in the LIPA gene. One allele carried a heterozygous 1-bp deletion (482delA) in exon 5, resulting in a frameshift and premature termination at residue 179. The mutation, which was inherited from the unaffected father, was not found in 200 controls chromosomes. The other allele, inherited from the unaffected mother, carried an intragenic deletion including intron 3 and part of exon 4; both the patient and mother had only 1 copy of exon 4. The patient presented at age 6 weeks with abdominal distention and failure to thrive. He had hepatosplenomegaly and calcified adrenals; LIPA activity was undetectable. He died of multiorgan failure within the following month. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21963785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CHOLESTERYL ESTER STORAGE DISEASE</strong>
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LIPA, c.600G-A
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1172318248 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1172318248;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=rs1172318248" 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=rs1172318248" 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=RCV001075889 OR RCV001449673 OR RCV001862637" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001075889, RCV001449673, RCV001862637" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001075889...</a>
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<p>In an Azerbaijani girl, born to consanguineous parents, with cholesteryl ester storage disease (CESD; <a href="/entry/278000">278000</a>), <a href="#6" class="mim-tip-reference" title="Bychkov, I. O., Kamenets, E. A., Filatova, A. Y., Skoblov, M. Y., Mikhaylova, S. V., Strokova, T. V., Gundobina, O. S., Zakharova, E. Y. <strong>The novel synonymous variant in LIPA gene affects splicing and causes lysosomal acid lipase deficiency.</strong> Molec. Genet. Metab. 127: 212-215, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31230978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31230978</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.06.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31230978">Bychkov et al. (2019)</a> identified homozygosity for a synonymous c.600G-A transition in exon 6 of the LIPA gene that was predicted to result in abnormal splicing. The mutation was identified by direct gene sequencing, and both parents were confirmed to be carriers. The mutation was not present in the ExAC and gnomAD databases or in 100 control chromosomes. Analysis of patient mRNA showed a deletion of 63-bp (c.539_601del) in exon 6 of the LIPA transcript, corresponding to activation of a cryptic splice site, and analysis of her parent's mRNA showed both the expected wildtype transcript and a transcript with the 63-bp deletion in exon 6. Molecular modeling predicted that the deletion was located close to the active site, affecting highly conserved amino acids, and likely had an impact on protein activity. Lysosomal acid lipase activity was low in patient leukocytes and in a dried blood spot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31230978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>See Also:</strong>
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<a href="#Muntoni1996" class="mim-tip-reference" title="Muntoni, S., Wiebusch, H., Funke, H., Seedorf, U., Roskos, M., Schulte, H., Saku, K., Arakawa, K., Balestrieri, A., Assmann, G. <strong>A missense mutation (Thr-6Pro) in the lysosomal acid lipase (LAL) gene is present with a high frequency in three different ethnic populations: impact on serum lipoprotein concentrations.</strong> Hum. Genet. 97: 265-267, 1996.">Muntoni et al. (1996)</a>
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<strong>REFERENCES</strong>
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<a id="Anderson1994" class="mim-anchor"></a>
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Anderson, R. A., Byrum, R. S., Coates, P. M., Sando, G. N.
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<strong>Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8146180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8146180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8146180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.91.7.2718" target="_blank">Full Text</a>]
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Anderson, R. A., Rao, N., Byrum, R. S., Rothschild, C. B., Bowden, D. W., Hayworth, R., Pettenati, M.
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<strong>In situ localization of the genetic locus encoding the lysosomal acid lipase/cholesteryl esterase (LIPA) deficient in Wolman disease to chromosome 10q23.2-q23.3.</strong>
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Genomics 15: 245-247, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432549</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432549" 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.1993.1052" target="_blank">Full Text</a>]
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<a id="Anderson1991" class="mim-anchor"></a>
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Anderson, R. A., Sando, G. N.
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<strong>Cloning and expression of cDNA encoding human lysosomal acid lipase/cholesteryl ester hydrolase: similarities to gastric and lingual lipases.</strong>
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J. Biol. Chem. 266: 22479-22484, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1718995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1718995</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1718995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Aslanidis, C., Klima, H., Lackner, K. J., Schmitz, G.
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<strong>Genomic organization of the human lysosomal acid lipase gene (LIPA).</strong>
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Genomics 20: 329-331, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8020990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8020990</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8020990" 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.1994.1180" target="_blank">Full Text</a>]
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Aslanidis, C., Ries, S., Fehringer, P., Buchler, C., Klima, H., Schmitz, G.
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<strong>Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity.</strong>
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Genomics 33: 85-93, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8617513/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8617513</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8617513" 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.1996.0162" target="_blank">Full Text</a>]
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Bychkov, I. O., Kamenets, E. A., Filatova, A. Y., Skoblov, M. Y., Mikhaylova, S. V., Strokova, T. V., Gundobina, O. S., Zakharova, E. Y.
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<strong>The novel synonymous variant in LIPA gene affects splicing and causes lysosomal acid lipase deficiency.</strong>
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Molec. Genet. Metab. 127: 212-215, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31230978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31230978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31230978" 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.ymgme.2019.06.005" target="_blank">Full Text</a>]
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Fujiyama, J., Sakuraba, H., Kuriyama, M., Fujita, T., Nagata, K., Nakagawa, H., Osame, M.
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<strong>A new mutation (LIPA Tyr22X) of lysosomal acid lipase gene in a Japanese patient with Wolman disease.</strong>
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Hum. Mutat. 8: 377-380, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8956047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8956047</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8956047" 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/(SICI)1098-1004(1996)8:4<377::AID-HUMU15>3.0.CO;2-#" target="_blank">Full Text</a>]
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Klima, H., Ullrich, K., Aslanidis, C., Fehringer, P., Lackner, K. J., Schmitz, G.
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<strong>A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.</strong>
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J. Clin. Invest. 92: 2713-2718, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8254026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8254026</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8254026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI116888" target="_blank">Full Text</a>]
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<a id="Koch1979" class="mim-anchor"></a>
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Koch, G. A., McAvoy, M., Naylor, S. L., Byers, M. G., Haley, L. L., Eddy, R. L., Brown, J. A., Shows, T. B.
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<strong>Assignment of lipase A (LIPA) to human chromosome 10. (Abstract)</strong>
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Koch, G., Lalley, P. A., McAvoy, M., Shows, T. B.
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<strong>Assignment of LIPA, associated with human acid lipase deficiency to human chromosome 10 and comparative assignment to mouse chromosome 19.</strong>
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Somat. Cell Genet. 7: 345-358, 1981.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7292252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7292252</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7292252" 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/BF01538859" target="_blank">Full Text</a>]
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<a id="Lee2011" class="mim-anchor"></a>
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Lee, T. M., Welsh, M., Benhamed, S., Chung, W. K.
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<strong>Intragenic deletion as a novel type of mutation in Wolman disease.</strong>
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Molec. Genet. Metab. 104: 703-705, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21963785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21963785</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21963785" 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.ymgme.2011.09.006" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Maslen1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Maslen, C. L., Babcock, D., Illingworth, D. R.
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|
<strong>Occurrence of a mutation associated with Wolman disease in a family with cholesteryl ester storage disease.</strong>
|
|
J. Inherit. Metab. Dis. 18: 620-623, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8598644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8598644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8598644" 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/BF02436008" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Maslen1993" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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|
Maslen, C. L., Illingworth, D. R.
|
|
<strong>Molecular genetics of cholesterol ester hydrolase deficiency. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 53 (suppl.): A926, 1993.
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Muntoni1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Muntoni, S., Wiebusch, H., Funke, H., Ros, E., Seedorf, U., Assmann, G.
|
|
<strong>Homozygosity for a splice junction mutation in exon 8 of the gene encoding lysosomal acid lipase in a Spanish kindred with cholesterol ester storage disease (CESD).</strong>
|
|
Hum. Genet. 95: 491-494, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7759067/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7759067</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7759067" 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/BF00223858" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Muntoni1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Muntoni, S., Wiebusch, H., Funke, H., Seedorf, U., Roskos, M., Schulte, H., Saku, K., Arakawa, K., Balestrieri, A., Assmann, G.
|
|
<strong>A missense mutation (Thr-6Pro) in the lysosomal acid lipase (LAL) gene is present with a high frequency in three different ethnic populations: impact on serum lipoprotein concentrations.</strong>
|
|
Hum. Genet. 97: 265-267, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8566968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8566968</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8566968" 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/BF02265280" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Pagani1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Pagani, F., Garcia, R., Pariyarath, R., Stuani, C., Gridelli, B., Paone, G., Baralle, F. E.
|
|
<strong>Expression of lysosomal acid lipase mutants detected in three patients with cholesteryl ester storage disease.</strong>
|
|
Hum. Molec. Genet. 5: 1611-1617, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8894696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8894696</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8894696" 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/5.10.1611" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Warner1980" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Warner, T. G., Dambach, L. M., Shin, J. H., O'Brien, J. S.
|
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<strong>Separation and characterization of the acid lipase and neutral esterases from human liver.</strong>
|
|
Am. J. Hum. Genet. 32: 869-879, 1980.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7446527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7446527</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7446527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 06/02/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 05/26/2021
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Anne M. Stumpf : 7/21/2010
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/02/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 12/06/2022<br>carol : 05/26/2021<br>carol : 12/22/2017<br>alopez : 12/22/2014<br>alopez : 7/18/2012<br>ckniffin : 7/12/2012<br>terry : 12/9/2010<br>alopez : 7/28/2010<br>alopez : 7/28/2010
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 613497
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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LIPASE A, LYSOSOMAL ACID; LIPA
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
LYSOSOMAL ACID LIPASE; LAL<br />
|
|
CHOLESTEROL ESTER HYDROLASE
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: LIPA</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> 57218003, 82500001;
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<strong>ICD10CM:</strong> E75.5;
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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: 10q23.31
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 10:89,213,572-89,251,775 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</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">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
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<th>
|
|
Phenotype
|
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</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
|
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<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
10q23.31
|
|
</span>
|
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</td>
|
|
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|
|
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<td>
|
|
<span class="mim-font">
|
|
Cholesteryl ester storage disease
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
278000
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Wolman disease
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
620151
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</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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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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<span class="mim-text-font">
|
|
<p>Anderson and Sando (1991) reported that the amino acid sequence of lysosomal acid lipase (LAL; cholesteryl ester hydrolase; EC 3.1.1.13) as deduced from the 2.6-kb cDNA nucleotide sequence is 58% identical to that of human gastric lipase (LIPF; 601980), which is involved in the preduodenal breakdown of ingested triglycerides. </p><p>Anderson et al. (1994) isolated and sequenced the gene for LIPA. </p>
|
|
</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>Gene Function</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>The distinct kinetic and physical properties of lipases A and B (LIPB; 247980) were defined by Warner et al. (1980). They stated that the natural substrate for LIPB was not known, and that it was not clear that LIPB is a lysosomal hydrolase. LIPA may serve an important role in cellular metabolism by releasing cholesterol. The liberated cholesterol suppresses further cholesterol synthesis and stimulates esterification of cholesterol within the cell. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
|
|
|
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|
|
<span class="mim-text-font">
|
|
<p>Aslanidis et al. (1994) summarized the exon structure of the LIPA gene, which consists of 10 exons, together with the sizes of genomic EcoRI and SacI fragments hybridizing to each exon. The DNA sequence of the putative promoter region was presented. </p><p>Anderson et al. (1994) found that the LIPA gene is spread over 36 kb of genomic DNA. The 5-prime flanking region is GC-rich and has characteristics of a 'housekeeping' gene promoter. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
|
<span class="mim-text-font">
|
|
<p>Koch et al. (1979, 1981) assigned lysosomal acid lipase A to chromosome 10 by human-Chinese hamster somatic cell hybrids. Judging from the close concordance with soluble glutamate oxaloacetate transaminase (GOT1; 138180), these loci were thought to be close together on the long arm of 10. Lipase A is encoded by chromosome 19 in mouse (Koch et al., 1981). GOT1 is also on chromosome 10q in man and 19 in mouse. </p><p>By fluorescence in situ hybridization, Anderson et al. (1993) mapped the LIPA locus to 10q23.2-q.23.3. It was clearly distinct from the locus for pancreatic lipase (246600) at 10q26.1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
|
<span class="mim-text-font">
|
|
<p>Cholesteryl ester storage disease (CESD; 278000) and Wolman disease (WOLD; 620151) are autosomal recessive allelic disorders associated with reduced activity and genetic defects of lysosomal acid lipase. Aslanidis et al. (1996) provided evidence that the strikingly more severe course of Wolman disease is caused by genetic defects of LAL that leave no residual enzyme activity. In a CESD patient, a G-to-A transition at position -1 of the exon 8 splice donor site (613497.0002) resulted in skipping of exon 8 in 97% of the mRNA originating from this allele, while 3% was spliced correctly, resulting in full-length LAL enzyme. Two sibs with Wolman disease were homozygous for a splice site mutation involving the same donor site but permitting no correct splicing or subsequent synthesis of functional enzyme (613497.0004). </p><p>Pagani et al. (1996) described the molecular basis of CESD in 3 patients. They identified mutations by sequence analysis of LAL cDNA and genomic DNA. The role of the mutations as the direct cause of the disease was confirmed by measuring the LAL enzymatic activity of extracts from cells transfected with LAL mutants. The 3 CESD patients were found to be compound heterozygotes. Pagani et al. (1996) identified 3 different missense mutations, 2 splicing defects, and a null allele. </p><p>In an Azerbaijani girl, born to consanguineous parents, with CESD, Bychkov et al. (2019) identified homozygosity for a synonymous mutation in the LIPS gene (613497.0008) that was predicted to result in abnormal splicing. Analysis of patient mRNA showed a deletion of 63-bp in exon 6 of the LIPA transcript, corresponding to activation of a cryptic splice site. The parents were found to be heterozygous for the mutation. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>8 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 WOLMAN 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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CHOLESTERYL ESTER STORAGE DISEASE, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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LIPA, LEU179PRO
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<br />
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SNP: rs121965086,
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gnomAD: rs121965086,
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ClinVar: RCV000000095, RCV000000096
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p />
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<p><strong><em>Wolman Disease</em></strong></p><p>
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In a proband with Wolman disease (WOLD; 620151) from a nonconsanguineous family, Anderson et al. (1994) detected a T-to-C transition at nucleotide 639 of the LIPA gene that resulted in a nonconservative missense mutation, leu179 to pro (L179P). This mutation was found in compound heterozygosity with a single-base insertion resulting in a null allele (613497.0004). The proband had had 2 older sibs with Wolman disease. Anderson et al. (1994) noted that the L179P mutation is located 26 amino acids from the predicted active site of lysosomal acid lipase and was expected to disrupt the alpha-helical structure in a highly conserved region of the protein. </p><p><strong><em>Cholesteryl Ester Storage Disease</em></strong></p><p>
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Maslen and Illingworth (1993) and Maslen et al. (1995) found the L179P mutation in 2 sibs with cholesteryl ester storage disease (CESD; 278000). In these sibs the L179P mutation, inherited from the mother, was found in compound heterozygosity with a splice site mutation that resulted in skipping of exon 8 of lysosomal acid lipase (613497.0002). Maslen et al. (1995) compared the phenotypes of other patients carrying the L179P or the splice site mutation described by them and concluded that the L179P mutant allele apparently does not make a substantial contribution to cholesteryl ester hydrolase activity. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CHOLESTERYL ESTER STORAGE 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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LIPA, 934G-A
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<br />
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SNP: rs116928232,
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gnomAD: rs116928232,
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ClinVar: RCV000185528, RCV000478829, RCV000778291, RCV001376623, RCV001823874, RCV002372140, RCV005003537
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 12-year-old patient with cholesteryl ester storage disease (CESD; 278000) from a nonconsanguineous Polish-German family, Klima et al. (1993) detected a 72-bp in-frame deletion resulting in the loss of amino acid codons 254 through 277. Analysis of genomic DNA revealed that the 72 bp represented an exon, indicating that the deletion in the mRNA was caused by defective splicing. Sequence analysis of the patient's genomic DNA revealed a G-to-A substitution in the last nucleotide of the 72-bp exon on 1 allele. No normal-sized mRNA was detectable in the propositus even though he was not homozygous for the splice site mutation. Klima et al. (1993) concluded that the patient was compound heterozygous for the splice site mutation and a null allele. The patient showed LIPA activity in cultured skin fibroblasts approximately 9% of normal. Hepatosplenomegaly had been present since age 5 years. </p><p>Aslanidis et al. (1996) restudied the patient of Klima et al. (1993) and defined the splice site mutation as a G-to-A mutation at position -1 of the splice donor site following exon 8, resulting in incorrect splicing and the removal of the 72-bp exon 8 of the LIPA gene. They determined that the other allele of the patient carried a premature termination mutation (613497.0003) as well as the L179P mutation (613497.0001); the LIPA mRNA was rendered unstable by the premature stop codon. Aslanidis et al. (1996) demonstrated that the splice site mutation allowed the production of approximately 3 to 4% of correctly spliced mRNA relative to wildtype. Aslanidis et al. (1996) also identified a mutation at the same splice donor site, and also resulting in deletion of exon 8, in 2 sibs with Wolman disease; that mutation, at the +1 position, allowed no correct splicing, and patient fibroblasts were devoid of enzymatic activity. See 613497.0005. </p><p>In 2 sibs with CESD, Maslen and Illingworth (1993) and Maslen et al. (1995) identified compound heterozygosity for this splice site mutation in the LIPA gene, inherited from their father, and the L179P mutation (613497.0001). The affected children were a sister and brother who presented with idiopathic hepatomegaly at ages 6 and 8 years, respectively. Subsequent analyses indicated that they also had hypercholesterolemia and a severe reduction in cholesteryl ester hydrolase activity in cultured fibroblasts. </p><p>Muntoni et al. (1995) observed homozygosity for the splice site mutation (Klima et al., 1993) in a Spanish kindred with cholesterol ester storage disease. Exon 8 of the LIPA gene was deleted. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 CHOLESTERYL ESTER STORAGE 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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LIPA, GLY245TER
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<br />
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SNP: rs267607218,
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gnomAD: rs267607218,
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ClinVar: RCV000000097, RCV001376562, RCV001562238, RCV001804146, RCV005041960
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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>Aslanidis et al. (1996) determined that the patient of Klima et al. (1993) with cholesteryl ester storage disease (CESD; 278000) was compound heterozygous for a G-to-T transversion at nucleotide 836 in exon 7 of the LIPA gene, resulting in substitution of gly245 with a termination codon (G245X), and a splice site mutation resulting in skipping of exon 8 (613497.0002). The allele carrying the G245X mutation also carried the L179P mutation (613497.0001). Aslanidis et al. (1996) concluded that although the L179P mutation is believed to abolish the enzymatic activity of the lysosomal acid lipase, it is the G245X mutation, through its production of an unstable mRNA, that was responsible for the low level of transcript (approximately 6% of wildtype) derived from the paternal allele. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 WOLMAN DISEASE</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
CHOLESTERYL ESTER STORAGE DISEASE, INCLUDED
|
|
</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
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LIPA, 1-BP INS, 634T
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<br />
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|
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SNP: rs780495201,
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|
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gnomAD: rs780495201,
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|
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ClinVar: RCV000000099, RCV000000100, RCV000524544, RCV001549751, RCV004734493
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|
|
|
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</span>
|
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</div>
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Wolman Disease</em></strong></p><p>
|
|
In a proband with Wolman disease (WOLD; 620151), Anderson et al. (1994) found compound heterozygosity for insertion of a T nucleotide after nucleotide 634 in exon 6 of the LIPA gene, and a substitution of proline at leucine-179 (613497.0001). The 634T insertion occurred at the end of a run of 6 Ts and led to premature termination 12 amino acids downstream. </p><p><strong><em>Cholesteryl Ester Storage Disease</em></strong></p><p>
|
|
Anderson et al. (1994) also found this mutation in a proband and parent from 1 of 11 unrelated families with cholesteryl ester storage disease (CESD; 278000) examined. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 WOLMAN DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
LIPA, IVS8, G-A, +1
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs1564751995,
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|
|
|
|
|
|
|
ClinVar: RCV000000101
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with Wolman disease (WOLD; 620151) from a consanguineous family, Aslanidis et al. (1996) detected homozygosity for a G-to-A mutation at position +1 of the splice donor site following exon 8 of the LIPA gene. Both children died within the first year of life. The parents, who were heterozygous for the mutation, had reduced enzymatic activity, while no enzymatic activity was detectable in fibroblasts from the affected children. Although the same donor splice site is involved in the mutation reported in CESD (934G-A, 613497.0002), the nucleotide at position +1 was changed in the Wolman disease mutation whereas the nucleotide at position -1 was changed in the CESD mutation. Both mutations result in deletion of the same 24 amino acids (exon 8), but the effects are dramatically different: the -1 mutation allowed some correct splicing (3% of total LIPA RNA), but the +1 splice site mutation, which affects one of the invariable nucleotides of the splice consensus sequences, permits no correct splicing. Aslanidis et al. (1996) suggested that the residual activity in CESD patients compared to Wolman patients may result either from a partially active enzyme with the internal deletion of 24 amino acids (skipping of exon 8) or from the production of low amounts of the full size of the protein due to inefficient exon exclusion from the mutated allele. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 WOLMAN DISEASE</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
LIPA, TYR22TER
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<br />
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|
|
SNP: rs121965087,
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|
|
ClinVar: RCV000000102
|
|
|
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|
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</span>
|
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</div>
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with Wolman disease (WOLD; 620151), Fujiyama et al. (1996) identified a tyr22-to-ter (Y22X) mutation of the LIPA gene. The female patient had an umbilical cord herniation at birth. At about 30 days after birth, she showed abdominal distention with hepatosplenomegaly and frequent episodes of diarrhea and vomiting. Abdominal computed tomography revealed massive hepatosplenomegaly and enlargement of the adrenal glands with calcification. Anemia and hepatic failure progressed rapidly and she died at age 114 days. The parents were first cousins. An older sister had died with similar symptoms 80 days after birth. </p>
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|
</span>
|
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</div>
|
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<div>
|
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<br />
|
|
</div>
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|
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</div>
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 WOLMAN DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
LIPA, 1-BP DEL, 482A
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|
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<br />
|
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|
|
SNP: rs762559980,
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|
|
|
gnomAD: rs762559980,
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|
|
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ClinVar: RCV000029177, RCV000667513
|
|
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|
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</span>
|
|
</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant, born of unrelated parents, with Wolman disease (WOLD; 620151), Lee et al. (2011) identified compound heterozygous mutations in the LIPA gene. One allele carried a heterozygous 1-bp deletion (482delA) in exon 5, resulting in a frameshift and premature termination at residue 179. The mutation, which was inherited from the unaffected father, was not found in 200 controls chromosomes. The other allele, inherited from the unaffected mother, carried an intragenic deletion including intron 3 and part of exon 4; both the patient and mother had only 1 copy of exon 4. The patient presented at age 6 weeks with abdominal distention and failure to thrive. He had hepatosplenomegaly and calcified adrenals; LIPA activity was undetectable. He died of multiorgan failure within the following month. </p>
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</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CHOLESTERYL ESTER STORAGE DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
LIPA, c.600G-A
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|
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|
|
<br />
|
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|
|
SNP: rs1172318248,
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|
|
|
|
ClinVar: RCV001075889, RCV001449673, RCV001862637
|
|
|
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|
|
</span>
|
|
</div>
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|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Azerbaijani girl, born to consanguineous parents, with cholesteryl ester storage disease (CESD; 278000), Bychkov et al. (2019) identified homozygosity for a synonymous c.600G-A transition in exon 6 of the LIPA gene that was predicted to result in abnormal splicing. The mutation was identified by direct gene sequencing, and both parents were confirmed to be carriers. The mutation was not present in the ExAC and gnomAD databases or in 100 control chromosomes. Analysis of patient mRNA showed a deletion of 63-bp (c.539_601del) in exon 6 of the LIPA transcript, corresponding to activation of a cryptic splice site, and analysis of her parent's mRNA showed both the expected wildtype transcript and a transcript with the 63-bp deletion in exon 6. Molecular modeling predicted that the deletion was located close to the active site, affecting highly conserved amino acids, and likely had an impact on protein activity. Lysosomal acid lipase activity was low in patient leukocytes and in a dried blood spot. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Muntoni et al. (1996)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
|
<ol>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Anderson, R. A., Byrum, R. S., Coates, P. M., Sando, G. N.
|
|
<strong>Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 2718-2722, 1994.
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|
[PubMed: 8146180]
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[Full Text: https://doi.org/10.1073/pnas.91.7.2718]
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</p>
|
|
</li>
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<li>
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<p class="mim-text-font">
|
|
Anderson, R. A., Rao, N., Byrum, R. S., Rothschild, C. B., Bowden, D. W., Hayworth, R., Pettenati, M.
|
|
<strong>In situ localization of the genetic locus encoding the lysosomal acid lipase/cholesteryl esterase (LIPA) deficient in Wolman disease to chromosome 10q23.2-q23.3.</strong>
|
|
Genomics 15: 245-247, 1993.
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|
|
[PubMed: 8432549]
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[Full Text: https://doi.org/10.1006/geno.1993.1052]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Anderson, R. A., Sando, G. N.
|
|
<strong>Cloning and expression of cDNA encoding human lysosomal acid lipase/cholesteryl ester hydrolase: similarities to gastric and lingual lipases.</strong>
|
|
J. Biol. Chem. 266: 22479-22484, 1991.
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|
[PubMed: 1718995]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Aslanidis, C., Klima, H., Lackner, K. J., Schmitz, G.
|
|
<strong>Genomic organization of the human lysosomal acid lipase gene (LIPA).</strong>
|
|
Genomics 20: 329-331, 1994.
|
|
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