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Entry
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- *613468 - N-ACYLSPHINGOSINE AMIDOHYDROLASE 1; ASAH1
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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">*613468</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/613468">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000104763;t=ENST00000637790" 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=427" 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=613468" 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 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=ENSG00000104763;t=ENST00000637790" 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_001127505,NM_001363743,NM_004315,NM_177924,XM_005273504" 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_177924" 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=613468" 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/ASAH1" 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/1743867,3860240,9651702,10437678,16741292,16877108,34559851,62897119,119584195,119584196,119584197,119584198,119584199,158259985,169403820,169403821,169403823,169403824,169403826,169403828,169403829,169403831,169403833,169403834,169403836,169403837,169403839,169403841,169403843,169403844,169403846,169403847,169403849,169403850,169403852,169403853,169403855,169403856,169403858,169403860,169403862,169403863,169403865,169403866,169403868,169403869,169403871,169403873,169403875,169403876,169403878,169403879,169403881,169403883,169403884,169403886,169403887,169403889,169403891,169403893,169403895,169403897,169403899,169403900,169403902,169403903,169403905,169403906,169403908,169403909,169403911,169403912,169403914,189011546,189011548,189011550,193783697,239938949,530387776,1393169623,2462619413" 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/Q13510" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=427" 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=ENSG00000104763;t=ENST00000637790" 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=ASAH1" 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=ASAH1" 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+427" 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/ASAH1" 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:427" 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/427" 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=chr8&hgg_gene=ENST00000637790.2&hgg_start=18055992&hgg_end=18084961&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:735" 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:735" 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/asah1" 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=613468[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=613468[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/ENSG00000104763" 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=ASAH1" 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=ASAH1" 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=ASAH1" 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=ASAH1&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/PA35025" 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:735" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1277124" 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/ASAH1#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:1277124" 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/427/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=427" 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=WBGene00009192;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00009192 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00010769;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00010769 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1512" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:427" 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=ASAH1&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> 703524005, 79935000<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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613468
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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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N-ACYLSPHINGOSINE AMIDOHYDROLASE 1; ASAH1
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ASAH<br />
|
|
N-ACYLSPHINGOSINE DEACYLASE<br />
|
|
ACID CERAMIDASE; AC<br />
|
|
ACID CDase<br />
|
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ACDase
|
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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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ASAH1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ASAH1</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/8/83?start=-3&limit=10&highlight=83">8p22</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr8:18055992-18084961&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'})">8:18,055,992-18,084,961</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=228000,159950" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/8/83?start=-3&limit=10&highlight=83">
|
|
8p22
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Farber lipogranulomatosis
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/228000"> 228000 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
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<p>N-acylsphingosine amidohydrolase (ASAH1; <a href="https://enzyme.expasy.org/EC/3.5.1.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 3.5.1.23</a>), or acid ceramidase (AC), is responsible for the degradation of ceramide into sphingosine and free fatty acids within lysosomes. ASAH1 also has 'reverse' enzymatic activity, in that it can synthesize ceramide from sphingosine and free fatty acids. The ASAH1 synthesis reaction occurs at a pH distinct from that of the hydrolysis reaction (6.0 vs 4.5, respectively), suggesting that ASAH1 may have diverse functions within cells depending on its subcellular location and the local pH (review by <a href="#13" class="mim-tip-reference" title="Park, J. H., Schuchman, E. H. <strong>Acid ceramidase and human disease.</strong> Biochim. Biophys. Acta 1758: 2133-2138, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17064658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17064658</a>] [<a href="https://doi.org/10.1016/j.bbamem.2006.08.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17064658">Park and Schuchman, 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17064658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#10" class="mim-tip-reference" title="Koch, J., Gartner, S., Li, C.-M., Quintern, L. E., Bernardo, K., Levran, O., Schnabel, D., Desnick, R. J., Schuchman, E. H., Sandhoff, K. <strong>Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase: identification of the first molecular lesion causing Farber disease.</strong> J. Biol. Chem. 271: 33110-33115, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955159/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955159</a>] [<a href="https://doi.org/10.1074/jbc.271.51.33110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955159">Koch et al. (1996)</a> purified acid ceramidase from urine and determined the 117 amino acid residues by microsequencing. Degenerative oligonucleotide probes were then constructed and used to screen human fibroblast and pituitary cDNA libraries. Several partial cDNA clones were obtained, and 2 of these combined to construct a full-length cDNA containing a 17-bp 5-prime untranslated sequence, a 1,185-bp open reading frame encoding 395 amino acids, a 110-bp 3-prime untranslated sequence, and an 18-bp poly(A) tail. Lysosomal acid ceramidase is a heterodimeric protein consisting of a nonglycosylated alpha subunit and a glycosylated beta subunit. The cDNA was found to encode both subunits, suggesting that the primary translation product of 395 amino acids is cleaved to the mature enzyme posttranslationally. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8955159" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using quantitative RT-PCR, <a href="#7" class="mim-tip-reference" title="Houben, E., Holleran, W. M., Yaginuma, T., Mao, C., Obeid, L. M., Rogiers, V., Takagi, Y., Elias, P. M., Uchida, Y. <strong>Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis.</strong> J. Lipid Res. 47: 1063-1070, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16477081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16477081</a>] [<a href="https://doi.org/10.1194/jlr.M600001-JLR200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16477081">Houben et al. (2006)</a> found that ACDase was expressed in all human tissues examined, with highest expression in heart and kidney. It was also expressed in all mouse tissues examined, with highest expression in kidney, followed by lung, heart, and brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16477081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#11" class="mim-tip-reference" title="Li, C.-M., Park, J.-H., He, X., Levy, B., Chen, F., Arai, K., Adler, D. A., Disteche, C. M., Koch, J., Sandhoff, K., Schuchman, E. H. <strong>The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis and expression.</strong> Genomics 62: 223-231, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610716</a>] [<a href="https://doi.org/10.1006/geno.1999.5940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610716">Li et al. (1999)</a> determined that the ASAH gene spans about 30 kb and contains 14 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10610716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By in situ hybridization and FISH analyses, <a href="#11" class="mim-tip-reference" title="Li, C.-M., Park, J.-H., He, X., Levy, B., Chen, F., Arai, K., Adler, D. A., Disteche, C. M., Koch, J., Sandhoff, K., Schuchman, E. H. <strong>The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis and expression.</strong> Genomics 62: 223-231, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610716</a>] [<a href="https://doi.org/10.1006/geno.1999.5940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610716">Li et al. (1999)</a> mapped the ASAH gene to chromosome 8p22-p21.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10610716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#13" class="mim-tip-reference" title="Park, J. H., Schuchman, E. H. <strong>Acid ceramidase and human disease.</strong> Biochim. Biophys. Acta 1758: 2133-2138, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17064658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17064658</a>] [<a href="https://doi.org/10.1016/j.bbamem.2006.08.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17064658">Park and Schuchman (2006)</a> reviewed acid ceramidase and its role in disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17064658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By combining genetic perturbation of sphingolipid metabolism with quantification of TLR (see <a href="/entry/601194">601194</a>) signaling steps and mass spectrometry-based lipidomics in mouse cells, <a href="#9" class="mim-tip-reference" title="Koberlin, M. S., Snijder, B., Heinz, L. X., Baumann, C. L., Fauster, A., Vladimer, G. I., Gavin, A.-C., Superti-Furga, G. <strong>A conserved circular network of coregulated lipids modulates innate immune responses.</strong> Cell 162: 170-183, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26095250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26095250</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26095250[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2015.05.051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26095250">Koberlin et al. (2015)</a> uncovered a circular network of coregulated sphingolipids and glycerophospholipids. Quantitative lipidomics on fibroblasts from patients with mutations in GBA (<a href="/entry/606463">606463</a>), GALC (<a href="/entry/606890">606890</a>), ASAH1, or LYST (<a href="/entry/606897">606897</a>) revealed conservation of the circular organization of lipid coregulation across species, cell types, and genetic perturbations. The functional annotation accurately predicted TLR-mediated inflammatory responses, in terms of changes in lipid abundance and lipid species, in patient cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26095250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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In a patient with Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>), <a href="#10" class="mim-tip-reference" title="Koch, J., Gartner, S., Li, C.-M., Quintern, L. E., Bernardo, K., Levran, O., Schnabel, D., Desnick, R. J., Schuchman, E. H., Sandhoff, K. <strong>Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase: identification of the first molecular lesion causing Farber disease.</strong> J. Biol. Chem. 271: 33110-33115, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955159/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955159</a>] [<a href="https://doi.org/10.1074/jbc.271.51.33110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955159">Koch et al. (1996)</a> identified a homoallelic thr222-to-lys (T222K; <a href="#0001">613468.0001</a>) mutation in the ASAH gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8955159" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bar, J., Linke, T., Ferlinz, K., Neumann, U., Schuchman, E. H., Sandhoff, K. <strong>Molecular analysis of acid ceramidase deficiency in patients with Farber disease.</strong> Hum. Mutat. 17: 199-209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11241842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11241842</a>] [<a href="https://doi.org/10.1002/humu.5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11241842">Bar et al. (2001)</a> identified 6 novel mutations in the ASAH gene causing Farber disease: 3 point mutations resulting in single amino acid substitutions, 1 intronic splice site mutation resulting in exon skipping, and 2 point mutations leading to occasional or complete exon skipping. The latter 2 mutations occurred in adjacent nucleotides and led to abnormal splicing of the same exon. Metabolic labeling studies in fibroblasts of 4 patients showed that even though acid ceramidase precursor protein was synthesized in these individuals, rapid proteolysis of the mutated, mature acid ceramidase occurred within the lysosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11241842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Muramatsu, T., Sakai, N., Yanagihara, I., Yamada, M., Nishigaki, T., Kokubu, C., Tsukamoto, H., Ito, M., Inui, K. <strong>Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease.</strong> J. Inherit. Metab. Dis. 25: 585-592, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12638942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12638942</a>] [<a href="https://doi.org/10.1023/a:1022047408477" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12638942">Muramatsu et al. (2002)</a> identified 3 novel mutations in the ASAH gene from 2 Japanese patients with Farber disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12638942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Indian sibs with Farber disease, who were born of consanguineous parents, <a href="#5" class="mim-tip-reference" title="Devi, A. R. R., Gopikrishna, M., Ratheesh, R., Savithri, G., Swarnalata, G., Bashyam, M. <strong>Farber lipogranulomatosis: clinical and molecular genetic analysis reveals a novel mutation in an Indian family.</strong> J. Hum. Genet. 51: 811-814, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16951918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16951918</a>] [<a href="https://doi.org/10.1007/s10038-006-0019-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16951918">Devi et al. (2006)</a> identified homozygosity for a missense mutation in the ASAH gene (<a href="#0005">613468.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16951918" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 Iranian sibs, aged 40, 58 and 60 years, with Farber disease, <a href="#4" class="mim-tip-reference" title="Bonafe, L., Kariminejad, A., Li, J., Royer-Bertrand, B., Garcia, V., Mahdavi, S., Bozorgmehr, B., Lachman, R. L., Mittaz-Crettol, L., Compos-Xavier, B., Nampoothiri, S., Unger, S., Rivolta, C., Levade, T., Superti-Furga, A. <strong>Peripheral osteolysis in adults linked to ASAH1 (acid ceramidase) mutations: a new presentation of Farber's disease.</strong> Arthritis Rheum. 68: 2323-2327, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26945816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26945816</a>] [<a href="https://doi.org/10.1002/art.39659" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26945816">Bonafe et al. (2016)</a> identified compound heterozygous mutations in the ASAH1 gene (<a href="#0012">613468.0012</a>-<a href="#0013">613468.0013</a>). The mutations were identified by whole-exome sequencing and segregated with disease in the family. Acid ceramidase enzyme activity in fibroblasts from 2 of the sibs were reduced to 7 to 8% of control levels. The patients had severe adult-onset peripheral osteolysis and a history of episodic fever and pain in childhood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26945816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 25-year-old woman with Farber disease, <a href="#2" class="mim-tip-reference" title="Bao, X., Ma, M., Zhang, Z., Xu, Y., Qui, Z. <strong>Farber disease in a patient from China.</strong> Am. J. Med. Genet. 182A: 2184-2186, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32706452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32706452</a>] [<a href="https://doi.org/10.1002/ajmg.a.61752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32706452">Bao et al. (2020)</a> identified compound heterozygous mutations in the ASAH1 gene. The mutations were identified by sequencing of the ASAH1 gene. The patient had osteolytic changes of the hands and toes and a history of nodules since infancy, hoarseness, joint swelling, and bone pain. She had a similarly affected brother who did not undergo genetic testing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32706452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review of acid ceramidase deficiency, <a href="#16" class="mim-tip-reference" title="Yu, F. B. S., Amintas, S., Levade, T., Medin, J. A. <strong>Acid ceramidase deficiency: Farber disease and SMA-PME.</strong> Orphanet J. Rare Dis. 13: 121, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30029679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30029679</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30029679[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1186/s13023-018-0845-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30029679">Yu et al. (2018)</a> noted that most of the mutations in the ASAH1 gene were missense mutations. A majority of the mutations associated with FRBRL were located within the beta subunit; 18 patients had mutations in exon 8, and 9 patients had mutations in exon 13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30029679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Spinal Muscular Atrophy With Progressive Myoclonic Epilepsy</em></strong></p><p>
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In 5 children from 2 families with spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME; <a href="/entry/159950">159950</a>), <a href="#17" class="mim-tip-reference" title="Zhou, J., Tawk, M., Tiziano, F. D., Veillet, J., Bayes, M., Nolent, F., Garcia, V., Servidei, S., Bertini, E., Castro-Giner, F., Renda, Y., Carpentier, S., Andrieu-Abadie, N., Gut, I., Levade, T., Topaloglu, H., Melki, J. <strong>Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1.</strong> Am. J. Hum. Genet. 91: 5-14, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22703880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22703880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22703880[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.05.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22703880">Zhou et al. (2012)</a> identified a homozygous mutation in the ASAH1 gene (T42M; <a href="#0006">613468.0006</a>). The mutation was identified by genomewide linkage analysis followed by exome sequencing. Another patient from a third family was found to be compound heterozygous for the T42M mutation and a deletion of the ASAH1 gene (<a href="#0007">613468.0007</a>). The T42M mutant protein was expressed in various patient tissues and showed decreased enzymatic activity (32% of controls) in in vitro functional studies, although the mutant enzyme still showed activity toward ceramide. The phenotype was characterized by childhood onset of proximal muscle weakness and muscular atrophy due to degeneration of spinal motor neurons, followed by the onset of myoclonic seizures. The disorder was progressive, and all patients died in the teenage years. Despite the severe phenotype, the disease course was less severe than that observed in Farber disease and symptoms appeared to be restricted to the central nervous system. <a href="#17" class="mim-tip-reference" title="Zhou, J., Tawk, M., Tiziano, F. D., Veillet, J., Bayes, M., Nolent, F., Garcia, V., Servidei, S., Bertini, E., Castro-Giner, F., Renda, Y., Carpentier, S., Andrieu-Abadie, N., Gut, I., Levade, T., Topaloglu, H., Melki, J. <strong>Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1.</strong> Am. J. Hum. Genet. 91: 5-14, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22703880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22703880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22703880[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.05.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22703880">Zhou et al. (2012)</a> postulated that the different phenotype in the SMAPME patients was related to residual levels of ASAH1 activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22703880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a girl with onset of SMAPME manifest as seizures at age 10 years, <a href="#6" class="mim-tip-reference" title="Dyment, D. A., Sell, E., Vanstone, M. R., Smith, A. C., Garandeau, D., Garcia, V., Carpentier, S., Le Trionnaire, E., Sabourdy, F., Beaulieu, C. L., Schwartzentruber, J. A., McMillan, H. J., FORGE Canada Consortium, Majewski, J., Bulman, D. E., Levade, T., Boycott, K. M. <strong>Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy.</strong> Clin. Genet. 86: 558-563, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24164096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24164096</a>] [<a href="https://doi.org/10.1111/cge.12307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24164096">Dyment et al. (2014)</a> identified compound heterozygous mutations in the ASAH1 gene (<a href="#0010">613468.0010</a> and <a href="#0011">613468.0011</a>). The mutations, which were found by whole-exome sequencing, segregated with the disorder in the family. Patient fibroblasts showed about 5.5% residual acid ceramidase activity and barely detectable levels of the beta subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24164096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between keloid formation (KLDF; <a href="/entry/148100">148100</a>) and variation in the ASAH1 gene, see <a href="#0016">613468.0016</a>.</p>
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<p><a href="#17" class="mim-tip-reference" title="Zhou, J., Tawk, M., Tiziano, F. D., Veillet, J., Bayes, M., Nolent, F., Garcia, V., Servidei, S., Bertini, E., Castro-Giner, F., Renda, Y., Carpentier, S., Andrieu-Abadie, N., Gut, I., Levade, T., Topaloglu, H., Melki, J. <strong>Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1.</strong> Am. J. Hum. Genet. 91: 5-14, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22703880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22703880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22703880[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.05.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22703880">Zhou et al. (2012)</a> observed that morpholino knockdown of the zebrafish ASAH1 ortholog Asah1b caused a significant increase of apoptosis specifically in the spinal cord, resulting in a curved body. In addition, morphant zebrafish showed decreased numbers of collateral branches in motor axons compared to controls. The morphant zebrafish had a decrease in, but not abrogation of, acid-ceramidase activity (about 26% of controls). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22703880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=613468[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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<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> rs137853593 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853593;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/rs137853593?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=rs137853593" 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=rs137853593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>), <a href="#10" class="mim-tip-reference" title="Koch, J., Gartner, S., Li, C.-M., Quintern, L. E., Bernardo, K., Levran, O., Schnabel, D., Desnick, R. J., Schuchman, E. H., Sandhoff, K. <strong>Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase: identification of the first molecular lesion causing Farber disease.</strong> J. Biol. Chem. 271: 33110-33115, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8955159/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8955159</a>] [<a href="https://doi.org/10.1074/jbc.271.51.33110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8955159">Koch et al. (1996)</a> identified a homozygous 665C-A transversion in the ASAH1 gene, resulting in a thr222-to-lys (T222K) substitution. The parents were consanguineous and heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8955159" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853594 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853594;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/rs137853594?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=rs137853594" 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=rs137853594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>), <a href="#11" class="mim-tip-reference" title="Li, C.-M., Park, J.-H., He, X., Levy, B., Chen, F., Arai, K., Adler, D. A., Disteche, C. M., Koch, J., Sandhoff, K., Schuchman, E. H. <strong>The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis and expression.</strong> Genomics 62: 223-231, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10610716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10610716</a>] [<a href="https://doi.org/10.1006/geno.1999.5940" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10610716">Li et al. (1999)</a> identified a glu138-to-val (E138V) mutation in the ASAH1 gene as a result of a 413A-T transversion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10610716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs137853595 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853595;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=rs137853595" 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=rs137853595" 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=RCV000000113" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000113" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000113</a>
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<p>In a male offspring of consanguineous Tunisian parents with the severe (classic) subtype of Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>) (<a href="#15" class="mim-tip-reference" title="Souillet, G., Guibaud, P., Fensom, A. H., Maire, I., Zabot, M. T. <strong>Outcome of displacement bone marrow transplantation in Farber's disease: a report of a case. In: Hobbs, J. R. (ed.): Correction of Certain Genetic Diseases by Transplantation.</strong> London: COGENT 1989. Pp. 137-141."None>Souillet et al., 1989</a>), <a href="#3" class="mim-tip-reference" title="Bar, J., Linke, T., Ferlinz, K., Neumann, U., Schuchman, E. H., Sandhoff, K. <strong>Molecular analysis of acid ceramidase deficiency in patients with Farber disease.</strong> Hum. Mutat. 17: 199-209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11241842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11241842</a>] [<a href="https://doi.org/10.1002/humu.5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11241842">Bar et al. (2001)</a> found a tyr36-to-cys (Y36C) mutation of the ASAH1 gene due to a 107A-G transition. The amino acid substitution was located in the alpha subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11241842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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ASAH1, ASN320ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853596 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853596;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=rs137853596" 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=rs137853596" 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=RCV000000114" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000114" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000114</a>
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<p>In a patient with Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>), <a href="#3" class="mim-tip-reference" title="Bar, J., Linke, T., Ferlinz, K., Neumann, U., Schuchman, E. H., Sandhoff, K. <strong>Molecular analysis of acid ceramidase deficiency in patients with Farber disease.</strong> Hum. Mutat. 17: 199-209, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11241842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11241842</a>] [<a href="https://doi.org/10.1002/humu.5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11241842">Bar et al. (2001)</a> described homozygosity for a 958A-G transition in the ASAH1 gene, resulting in an asn320-to-asp (N320D) substitution in the beta subunit of acid ceramidase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11241842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 FARBER LIPOGRANULOMATOSIS</strong>
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ASAH1, LEU182VAL
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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> rs137853597 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853597;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/rs137853597?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=rs137853597" 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=rs137853597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000000115" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000115" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000115</a>
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<p>In 2 Indian sibs with Farber disease (FRBRL; <a href="/entry/228000">228000</a>), who were born of consanguineous parents, <a href="#5" class="mim-tip-reference" title="Devi, A. R. R., Gopikrishna, M., Ratheesh, R., Savithri, G., Swarnalata, G., Bashyam, M. <strong>Farber lipogranulomatosis: clinical and molecular genetic analysis reveals a novel mutation in an Indian family.</strong> J. Hum. Genet. 51: 811-814, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16951918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16951918</a>] [<a href="https://doi.org/10.1007/s10038-006-0019-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16951918">Devi et al. (2006)</a> identified homozygosity for a C-to-G transversion in exon 8 of the ASAH1 gene, resulting in a leu182-to-val (L182V) substitution. The parents were heterozygous for the mutation, which was not found in 101 ethnically matched controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16951918" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY</strong>
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ASAH1, THR42MET
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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> rs145873635 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs145873635;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/rs145873635?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=rs145873635" 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=rs145873635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000029199 OR RCV000724837 OR RCV001270895" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000029199, RCV000724837, RCV001270895" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000029199...</a>
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<p>In 5 children from 2 families with spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME; <a href="/entry/159950">159950</a>), <a href="#17" class="mim-tip-reference" title="Zhou, J., Tawk, M., Tiziano, F. D., Veillet, J., Bayes, M., Nolent, F., Garcia, V., Servidei, S., Bertini, E., Castro-Giner, F., Renda, Y., Carpentier, S., Andrieu-Abadie, N., Gut, I., Levade, T., Topaloglu, H., Melki, J. <strong>Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1.</strong> Am. J. Hum. Genet. 91: 5-14, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22703880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22703880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22703880[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.05.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22703880">Zhou et al. (2012)</a> identified a homozygous 125C-T transition in the last nucleotide of exon 2 of the ASAH1 gene, resulting in a thr42-to-met (T42M) substitution at a highly conserved residue in the alpha-subunit. The mutation was not found in 95 controls, and was found at a very low frequency (2 of 10,756 alleles) in the Exome Variant Server database. Haplotype analysis suggested a founder effect. The mutation was identified by genomewide linkage analysis followed by exome sequencing. Another patient from a third family was found to be compound heterozygous for the T42M mutation and a deletion of the ASAH1 gene (<a href="#0007">613468.0007</a>). The T42M mutant protein was expressed in various patient tissues and showed decreased enzymatic activity (32% of controls) in in vitro functional studies, although the mutant enzyme still showed activity toward ceramide. Immunoblot experiments showed that the amount of the alpha-subunit was mildly lower than the beta subunit, suggesting that the mutation may affect the stability of the alpha-subunit and thus contribute to decreased enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22703880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY</strong>
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ASAH1, DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000029200" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000029200" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000029200</a>
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<p>For discussion of deletion of the ASAH1 gene that was found in compound heterozygous state in a patient with spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME; <a href="/entry/159950">159950</a>) by <a href="#17" class="mim-tip-reference" title="Zhou, J., Tawk, M., Tiziano, F. D., Veillet, J., Bayes, M., Nolent, F., Garcia, V., Servidei, S., Bertini, E., Castro-Giner, F., Renda, Y., Carpentier, S., Andrieu-Abadie, N., Gut, I., Levade, T., Topaloglu, H., Melki, J. <strong>Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1.</strong> Am. J. Hum. Genet. 91: 5-14, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22703880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22703880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22703880[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.05.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22703880">Zhou et al. (2012)</a>, see <a href="#0006">613468.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22703880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 FARBER LIPOGRANULOMATOSIS</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">rs397509415 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397509415;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=rs397509415" 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=rs397509415" 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=RCV000049322" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049322" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049322</a>
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<p>In a patient with a severe form of Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>) resulting in hydrops fetalis and death at age 3 days (<a href="#8" class="mim-tip-reference" title="Kattner, E., Schafer, A., Harzer, K. <strong>Hydrops fetalis: manifestation in lysosomal storage diseases including Farber disease.</strong> Europ. J. Pediat. 156: 292-295, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9128814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9128814</a>] [<a href="https://doi.org/10.1007/s004310050603" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9128814">Kattner et al., 1997</a>), <a href="#1" class="mim-tip-reference" title="Alves, M. Q., Le Trionnaire, E., Ribeiro, I., Carpentier, S., Harzer, K., Levade, T., Ribeiro, M. G. <strong>Molecular basis of acid ceramidase deficiency in a neonatal form of Farber disease: identification of the first large deletion in ASAH1 gene.</strong> Molec. Genet. Metab. 109: 276-281, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707712</a>] [<a href="https://doi.org/10.1016/j.ymgme.2013.04.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23707712">Alves et al. (2013)</a> identified compound heterozygous mutations in the ASAH1 gene: an A-to-G transition in intron 11 (c.917+4A-G), predicted to interfere with normal splicing, and a 9.4-kb deletion encompassing exons 3 to 5 (<a href="#0009">613468.0009</a>). Each unaffected parent was heterozygous for 1 of the mutations. Analysis of patient cells showed about 50% ASAH1 transcript compared to controls, but no detectable full-length transcript and no ASAH1 protein. The major abnormal transcript resulted from the deletion of exons 3 to 5, resulting in premature termination (Tyr42_Leu127delinsArgfsTer10). The patient's severe phenotype correlated with the 2 null ASAH1 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23707712+9128814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<strong>.0009 FARBER LIPOGRANULOMATOSIS</strong>
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ASAH1, 9.4-KB DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000656522" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000656522" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000656522</a>
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<p>For discussion of the 9.4-kb deletion in the ASAH1 gene that was found in compound heterozygous state in a patient with a severe form of Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>) by <a href="#1" class="mim-tip-reference" title="Alves, M. Q., Le Trionnaire, E., Ribeiro, I., Carpentier, S., Harzer, K., Levade, T., Ribeiro, M. G. <strong>Molecular basis of acid ceramidase deficiency in a neonatal form of Farber disease: identification of the first large deletion in ASAH1 gene.</strong> Molec. Genet. Metab. 109: 276-281, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707712</a>] [<a href="https://doi.org/10.1016/j.ymgme.2013.04.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23707712">Alves et al. (2013)</a>, see <a href="#0008">613468.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0010" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0010 SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY</strong>
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ASAH1, GLY284TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs794729663 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs794729663;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=rs794729663" 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=rs794729663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000157604" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000157604" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000157604</a>
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<span class="mim-text-font">
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<p>In a girl with onset of spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME; <a href="/entry/159950">159950</a>) at age 10 years, <a href="#6" class="mim-tip-reference" title="Dyment, D. A., Sell, E., Vanstone, M. R., Smith, A. C., Garandeau, D., Garcia, V., Carpentier, S., Le Trionnaire, E., Sabourdy, F., Beaulieu, C. L., Schwartzentruber, J. A., McMillan, H. J., FORGE Canada Consortium, Majewski, J., Bulman, D. E., Levade, T., Boycott, K. M. <strong>Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy.</strong> Clin. Genet. 86: 558-563, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24164096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24164096</a>] [<a href="https://doi.org/10.1111/cge.12307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24164096">Dyment et al. (2014)</a> identified compound heterozygous mutations in the ASAH1 gene: a c.850G-T transversion in exon 11, resulting in a gly284-to-ter (G284X) substitution, and a c.456A-C transversion (<a href="#0011">613468.0011</a>) in exon 6, predicted to result in a lys152-to-asn (K152N) substitution; however, cDNA from patient fibroblasts showed that the latter mutation caused aberrant splicing with the skipping of exon 6. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and were filtered against the 1000 Genomes Project (2012/04 release) and Exome Variant Server (ESP6500) databases, as well as 800 in-house control exomes. Patient fibroblasts showed about 5.5% residual acid ceramidase activity and barely detectable levels of the beta subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24164096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0011" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0011 SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY</strong>
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ASAH1, 456A-C
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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> rs200455852 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200455852;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/rs200455852?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=rs200455852" 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=rs200455852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000157605 OR RCV000853058 OR RCV004551355" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000157605, RCV000853058, RCV004551355" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000157605...</a>
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<span class="mim-text-font">
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<p>For discussion of the c.456A-C mutation in the ASAH1 gene that was found in compound heterozygous state in a patient with SMAPME (<a href="/entry/159950">159950</a>) by <a href="#6" class="mim-tip-reference" title="Dyment, D. A., Sell, E., Vanstone, M. R., Smith, A. C., Garandeau, D., Garcia, V., Carpentier, S., Le Trionnaire, E., Sabourdy, F., Beaulieu, C. L., Schwartzentruber, J. A., McMillan, H. J., FORGE Canada Consortium, Majewski, J., Bulman, D. E., Levade, T., Boycott, K. M. <strong>Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy.</strong> Clin. Genet. 86: 558-563, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24164096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24164096</a>] [<a href="https://doi.org/10.1111/cge.12307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24164096">Dyment et al. (2014)</a>, see <a href="#0010">613468.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24164096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0012" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0012 FARBER LIPOGRANULOMATOSIS</strong>
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ASAH1, TRP169ARG
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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> rs756455049 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs756455049;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/rs756455049?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=rs756455049" 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=rs756455049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000171533 OR RCV001728167" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000171533, RCV001728167" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000171533...</a>
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<p>In 3 Iranian sibs, aged 40, 58 and 60 years, with Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>), <a href="#4" class="mim-tip-reference" title="Bonafe, L., Kariminejad, A., Li, J., Royer-Bertrand, B., Garcia, V., Mahdavi, S., Bozorgmehr, B., Lachman, R. L., Mittaz-Crettol, L., Compos-Xavier, B., Nampoothiri, S., Unger, S., Rivolta, C., Levade, T., Superti-Furga, A. <strong>Peripheral osteolysis in adults linked to ASAH1 (acid ceramidase) mutations: a new presentation of Farber's disease.</strong> Arthritis Rheum. 68: 2323-2327, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26945816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26945816</a>] [<a href="https://doi.org/10.1002/art.39659" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26945816">Bonafe et al. (2016)</a> identified compound heterozygous mutations in the ASAH1 gene: a c.505T-C transition, resulting in a trp169-to-arg (W169R) substitution, and a c.760A-G transition, resulting in an arg254-to-gly (R254G; <a href="#0013">613468.0013</a>) substitution. The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with disease in the family. Acid ceramidase enzyme activity in fibroblasts from 2 of the sibs was reduced to 7 to 8% of control levels. The patients had severe adult-onset peripheral osteolysis and a history of episodic fever and pain in childhood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26945816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0013" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0013 FARBER LIPOGRANULOMATOSIS</strong>
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ASAH1, ARG254GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2117037405 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2117037405;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=rs2117037405" 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=rs2117037405" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the c.760A-G transition in the ASAH1 gene, resulting in an arg254-to-gly (R254G) substitution, that was identified in compound heterozygous state in 3 Iranian sibs with lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>) by <a href="#4" class="mim-tip-reference" title="Bonafe, L., Kariminejad, A., Li, J., Royer-Bertrand, B., Garcia, V., Mahdavi, S., Bozorgmehr, B., Lachman, R. L., Mittaz-Crettol, L., Compos-Xavier, B., Nampoothiri, S., Unger, S., Rivolta, C., Levade, T., Superti-Furga, A. <strong>Peripheral osteolysis in adults linked to ASAH1 (acid ceramidase) mutations: a new presentation of Farber's disease.</strong> Arthritis Rheum. 68: 2323-2327, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26945816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26945816</a>] [<a href="https://doi.org/10.1002/art.39659" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26945816">Bonafe et al. (2016)</a>, see <a href="#0012">613468.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26945816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 25-year-old woman with Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>), <a href="#2" class="mim-tip-reference" title="Bao, X., Ma, M., Zhang, Z., Xu, Y., Qui, Z. <strong>Farber disease in a patient from China.</strong> Am. J. Med. Genet. 182A: 2184-2186, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32706452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32706452</a>] [<a href="https://doi.org/10.1002/ajmg.a.61752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32706452">Bao et al. (2020)</a> identified compound heterozygous mutations in the ASAH1 gene: a c.427T-G transversion (c.427T-G, NM_177924.3), resulting in a cys143-to-gly (C143G) substitution, and a c.358G-C transversion, resulting in an ala120-to-pro (A120P; <a href="#0015">613468.0015</a>) substitution. The mutations were identified by sequencing of the ASAH1 gene, and the parents were shown to be mutation carriers. The patient had osteolytic changes of the hands and toes and a history of nodules since infancy, hoarseness, joint swelling, and bone pain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32706452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs2117047219 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2117047219;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=rs2117047219" 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=rs2117047219" 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=RCV001728067" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001728067" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001728067</a>
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<p>For discussion of the c.358G-C transversion (c.358G-C, NM_177924.3) in the ASAH1 gene, resulting in an ala120-to-pro (A120P) substitution, that was identified in compound heterozygous state in a patient with Farber lipogranulomatosis (FRBRL; <a href="/entry/228000">228000</a>) by <a href="#2" class="mim-tip-reference" title="Bao, X., Ma, M., Zhang, Z., Xu, Y., Qui, Z. <strong>Farber disease in a patient from China.</strong> Am. J. Med. Genet. 182A: 2184-2186, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32706452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32706452</a>] [<a href="https://doi.org/10.1002/ajmg.a.61752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32706452">Bao et al. (2020)</a>, see <a href="#0014">613468.0014</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32706452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0016 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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ASAH1, LEU401PRO (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs368345612;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs368345612</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> rs368345612 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs368345612;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/rs368345612?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=rs368345612" 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=rs368345612" 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=RCV000515786 OR RCV001851128 OR RCV002280815" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000515786, RCV001851128, RCV002280815" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000515786...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to keloid formation (KLDF; see <a href="/entry/148100">148100</a>) has not been confirmed.</p><p>In a large 3-generation Nigerian Yoruba family (family A) segregating autosomal dominant keloid formation mapping to chromosome 8p23-p21, <a href="#14" class="mim-tip-reference" title="Santos-Cortez, R. L. P., Hu, Y., Sun, F., Benahmed-Miniuk, F., Tao, J., Kanaujiya, J. K., Ademola, S., Fadiora, S., Odesina, V., University of Washington Center for Mendelian Genomics, Nickerson, D. A., Bamshad, M. J., Olaitan, P. B., Oluwatosin, O. M., Leal, S. M., Reichenberger, E. J. <strong>Identification of ASAH1 as a susceptibility gene for familial keloids.</strong> Europ. J. Hum. Genet. 25: 1155-1161, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28905881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28905881</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28905881[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2017.121" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28905881">Santos-Cortez et al. (2017)</a> identified heterozygosity for a c.1202T-C transition (c.1202T-C, NM_004315.5) in the ASAH1 gene resulting in a leu401-to-pro substitution (L401P) that was present in all 9 affected individuals as well as in 3 unaffected family members (III-10, III-12, and III-19). There were also 2 family members of unknown status, with hypertrophic or raised scars, 1 of whom (III-11) did not carry the mutation and 1 of whom (III-7) carried the haplotype but whose mutation status was not reported. Screening for the L401P variant in 318 patients with keloids identified 2 unrelated Nigerian probands with the variant. Analysis of exome variants surrounding the ASAH1 variant defined a 210.4-kb haplotype that was shared by members of family A and the 2 Nigerian probands. The L401P variant was not found in 192 unaffected Yoruba controls with no family history of keloids, but was present in 2 heterozygous African alleles (minor allele frequency, 0.00019) in the ExAC database. The authors noted that in family A, onset of keloid formation ranged from the first to the seventh decade of life; thus the 3 unaffected mutation carriers, who were under 33 years of age, might yet develop keloids. Because 2 family members developed a keloid and a normal scar at around the same age, and some family members developed keloids only at a late age, the authors hypothesized that additional factors that change over time must play a role, including environmental and/or genetic modifiers. The authors also noted that individuals heterozygous for ASAH1 variants causing Farber lipogranulomatosis (<a href="/entry/228000">228000</a>) or spinal muscular atrophy with progressive myoclonic epilepsy (<a href="/entry/159950">159950</a>) were not known to have increased risk for keloids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28905881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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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Alves, M. Q., Le Trionnaire, E., Ribeiro, I., Carpentier, S., Harzer, K., Levade, T., Ribeiro, M. G.
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<strong>Molecular basis of acid ceramidase deficiency in a neonatal form of Farber disease: identification of the first large deletion in ASAH1 gene.</strong>
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Molec. Genet. Metab. 109: 276-281, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707712" 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.2013.04.019" target="_blank">Full Text</a>]
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Bao, X., Ma, M., Zhang, Z., Xu, Y., Qui, Z.
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<strong>Farber disease in a patient from China.</strong>
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Am. J. Med. Genet. 182A: 2184-2186, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32706452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32706452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32706452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.61752" target="_blank">Full Text</a>]
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Bar, J., Linke, T., Ferlinz, K., Neumann, U., Schuchman, E. H., Sandhoff, K.
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<strong>Molecular analysis of acid ceramidase deficiency in patients with Farber disease.</strong>
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Hum. Mutat. 17: 199-209, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11241842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11241842</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11241842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.5" target="_blank">Full Text</a>]
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Bonafe, L., Kariminejad, A., Li, J., Royer-Bertrand, B., Garcia, V., Mahdavi, S., Bozorgmehr, B., Lachman, R. L., Mittaz-Crettol, L., Compos-Xavier, B., Nampoothiri, S., Unger, S., Rivolta, C., Levade, T., Superti-Furga, A.
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<strong>Peripheral osteolysis in adults linked to ASAH1 (acid ceramidase) mutations: a new presentation of Farber's disease.</strong>
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Arthritis Rheum. 68: 2323-2327, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26945816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26945816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26945816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10038-006-0019-z" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s004310050603" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.cell.2015.05.051" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.271.51.33110" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/geno.1999.5940" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1023/a:1022047408477" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ejhg.2017.121" target="_blank">Full Text</a>]
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Zhou, J., Tawk, M., Tiziano, F. D., Veillet, J., Bayes, M., Nolent, F., Garcia, V., Servidei, S., Bertini, E., Castro-Giner, F., Renda, Y., Carpentier, S., Andrieu-Abadie, N., Gut, I., Levade, T., Topaloglu, H., Melki, J.
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Marla J. F. O'Neill - updated : 09/02/2022
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Hilary J. Vernon - updated : 10/04/2021<br>Paul J. Converse - updated : 02/05/2016<br>Cassandra L. Kniffin - updated : 1/29/2015<br>Cassandra L. Kniffin - updated : 7/16/2013<br>Cassandra L. Kniffin - updated : 7/18/2012<br>Patricia A. Hartz - updated : 7/20/2010
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carol : 08/31/2023<br>alopez : 09/02/2022<br>carol : 10/04/2021<br>mgross : 02/05/2016<br>carol : 7/13/2015<br>mcolton : 7/10/2015<br>carol : 2/5/2015<br>mcolton : 2/2/2015<br>ckniffin : 1/29/2015<br>carol : 9/6/2013<br>carol : 7/17/2013<br>ckniffin : 7/16/2013<br>carol : 7/19/2012<br>ckniffin : 7/18/2012<br>terry : 12/8/2010<br>mgross : 7/20/2010<br>mgross : 7/2/2010
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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> 613468
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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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N-ACYLSPHINGOSINE AMIDOHYDROLASE 1; ASAH1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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ASAH<br />
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N-ACYLSPHINGOSINE DEACYLASE<br />
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ACID CERAMIDASE; AC<br />
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ACID CDase<br />
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ACDase
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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: ASAH1</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> 703524005, 79935000;
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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: 8p22
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Genomic coordinates <span class="small">(GRCh38)</span> : 8:18,055,992-18,084,961 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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8p22
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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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Farber lipogranulomatosis
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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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228000
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Spinal muscular atrophy with progressive myoclonic epilepsy
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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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159950
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>N-acylsphingosine amidohydrolase (ASAH1; EC 3.5.1.23), or acid ceramidase (AC), is responsible for the degradation of ceramide into sphingosine and free fatty acids within lysosomes. ASAH1 also has 'reverse' enzymatic activity, in that it can synthesize ceramide from sphingosine and free fatty acids. The ASAH1 synthesis reaction occurs at a pH distinct from that of the hydrolysis reaction (6.0 vs 4.5, respectively), suggesting that ASAH1 may have diverse functions within cells depending on its subcellular location and the local pH (review by Park and Schuchman, 2006). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Koch et al. (1996) purified acid ceramidase from urine and determined the 117 amino acid residues by microsequencing. Degenerative oligonucleotide probes were then constructed and used to screen human fibroblast and pituitary cDNA libraries. Several partial cDNA clones were obtained, and 2 of these combined to construct a full-length cDNA containing a 17-bp 5-prime untranslated sequence, a 1,185-bp open reading frame encoding 395 amino acids, a 110-bp 3-prime untranslated sequence, and an 18-bp poly(A) tail. Lysosomal acid ceramidase is a heterodimeric protein consisting of a nonglycosylated alpha subunit and a glycosylated beta subunit. The cDNA was found to encode both subunits, suggesting that the primary translation product of 395 amino acids is cleaved to the mature enzyme posttranslationally. </p><p>Using quantitative RT-PCR, Houben et al. (2006) found that ACDase was expressed in all human tissues examined, with highest expression in heart and kidney. It was also expressed in all mouse tissues examined, with highest expression in kidney, followed by lung, heart, and brain. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Li et al. (1999) determined that the ASAH gene spans about 30 kb and contains 14 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By in situ hybridization and FISH analyses, Li et al. (1999) mapped the ASAH gene to chromosome 8p22-p21.3. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Park and Schuchman (2006) reviewed acid ceramidase and its role in disease. </p><p>By combining genetic perturbation of sphingolipid metabolism with quantification of TLR (see 601194) signaling steps and mass spectrometry-based lipidomics in mouse cells, Koberlin et al. (2015) uncovered a circular network of coregulated sphingolipids and glycerophospholipids. Quantitative lipidomics on fibroblasts from patients with mutations in GBA (606463), GALC (606890), ASAH1, or LYST (606897) revealed conservation of the circular organization of lipid coregulation across species, cell types, and genetic perturbations. The functional annotation accurately predicted TLR-mediated inflammatory responses, in terms of changes in lipid abundance and lipid species, in patient cells. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Farber Lipogranulomatosis</em></strong></p><p>
|
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In a patient with Farber lipogranulomatosis (FRBRL; 228000), Koch et al. (1996) identified a homoallelic thr222-to-lys (T222K; 613468.0001) mutation in the ASAH gene. </p><p>Bar et al. (2001) identified 6 novel mutations in the ASAH gene causing Farber disease: 3 point mutations resulting in single amino acid substitutions, 1 intronic splice site mutation resulting in exon skipping, and 2 point mutations leading to occasional or complete exon skipping. The latter 2 mutations occurred in adjacent nucleotides and led to abnormal splicing of the same exon. Metabolic labeling studies in fibroblasts of 4 patients showed that even though acid ceramidase precursor protein was synthesized in these individuals, rapid proteolysis of the mutated, mature acid ceramidase occurred within the lysosome. </p><p>Muramatsu et al. (2002) identified 3 novel mutations in the ASAH gene from 2 Japanese patients with Farber disease. </p><p>In 2 Indian sibs with Farber disease, who were born of consanguineous parents, Devi et al. (2006) identified homozygosity for a missense mutation in the ASAH gene (613468.0005). </p><p>In 3 Iranian sibs, aged 40, 58 and 60 years, with Farber disease, Bonafe et al. (2016) identified compound heterozygous mutations in the ASAH1 gene (613468.0012-613468.0013). The mutations were identified by whole-exome sequencing and segregated with disease in the family. Acid ceramidase enzyme activity in fibroblasts from 2 of the sibs were reduced to 7 to 8% of control levels. The patients had severe adult-onset peripheral osteolysis and a history of episodic fever and pain in childhood. </p><p>In a 25-year-old woman with Farber disease, Bao et al. (2020) identified compound heterozygous mutations in the ASAH1 gene. The mutations were identified by sequencing of the ASAH1 gene. The patient had osteolytic changes of the hands and toes and a history of nodules since infancy, hoarseness, joint swelling, and bone pain. She had a similarly affected brother who did not undergo genetic testing. </p><p>In a review of acid ceramidase deficiency, Yu et al. (2018) noted that most of the mutations in the ASAH1 gene were missense mutations. A majority of the mutations associated with FRBRL were located within the beta subunit; 18 patients had mutations in exon 8, and 9 patients had mutations in exon 13. </p><p><strong><em>Spinal Muscular Atrophy With Progressive Myoclonic Epilepsy</em></strong></p><p>
|
|
In 5 children from 2 families with spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME; 159950), Zhou et al. (2012) identified a homozygous mutation in the ASAH1 gene (T42M; 613468.0006). The mutation was identified by genomewide linkage analysis followed by exome sequencing. Another patient from a third family was found to be compound heterozygous for the T42M mutation and a deletion of the ASAH1 gene (613468.0007). The T42M mutant protein was expressed in various patient tissues and showed decreased enzymatic activity (32% of controls) in in vitro functional studies, although the mutant enzyme still showed activity toward ceramide. The phenotype was characterized by childhood onset of proximal muscle weakness and muscular atrophy due to degeneration of spinal motor neurons, followed by the onset of myoclonic seizures. The disorder was progressive, and all patients died in the teenage years. Despite the severe phenotype, the disease course was less severe than that observed in Farber disease and symptoms appeared to be restricted to the central nervous system. Zhou et al. (2012) postulated that the different phenotype in the SMAPME patients was related to residual levels of ASAH1 activity. </p><p>In a girl with onset of SMAPME manifest as seizures at age 10 years, Dyment et al. (2014) identified compound heterozygous mutations in the ASAH1 gene (613468.0010 and 613468.0011). The mutations, which were found by whole-exome sequencing, segregated with the disorder in the family. Patient fibroblasts showed about 5.5% residual acid ceramidase activity and barely detectable levels of the beta subunit. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between keloid formation (KLDF; 148100) and variation in the ASAH1 gene, see 613468.0016.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Animal Model</strong>
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
|
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<p>Zhou et al. (2012) observed that morpholino knockdown of the zebrafish ASAH1 ortholog Asah1b caused a significant increase of apoptosis specifically in the spinal cord, resulting in a curved body. In addition, morphant zebrafish showed decreased numbers of collateral branches in motor axons compared to controls. The morphant zebrafish had a decrease in, but not abrogation of, acid-ceramidase activity (about 26% of controls). </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>16 Selected Examples):</strong>
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</span>
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</h4>
|
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<div>
|
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<p />
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0001 FARBER LIPOGRANULOMATOSIS</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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ASAH1, THR222LYS
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<br />
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SNP: rs137853593,
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gnomAD: rs137853593,
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ClinVar: RCV000000111
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
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<p>In a patient with Farber lipogranulomatosis (FRBRL; 228000), Koch et al. (1996) identified a homozygous 665C-A transversion in the ASAH1 gene, resulting in a thr222-to-lys (T222K) substitution. The parents were consanguineous and heterozygous for the mutation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0002 FARBER LIPOGRANULOMATOSIS</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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ASAH1, GLU138VAL
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<br />
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SNP: rs137853594,
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gnomAD: rs137853594,
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ClinVar: RCV000000112, RCV000853547
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with Farber lipogranulomatosis (FRBRL; 228000), Li et al. (1999) identified a glu138-to-val (E138V) mutation in the ASAH1 gene as a result of a 413A-T transversion. </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 FARBER LIPOGRANULOMATOSIS</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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ASAH1, TYR36CYS
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<br />
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SNP: rs137853595,
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ClinVar: RCV000000113
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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 male offspring of consanguineous Tunisian parents with the severe (classic) subtype of Farber lipogranulomatosis (FRBRL; 228000) (Souillet et al., 1989), Bar et al. (2001) found a tyr36-to-cys (Y36C) mutation of the ASAH1 gene due to a 107A-G transition. The amino acid substitution was located in the alpha subunit. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0004 FARBER LIPOGRANULOMATOSIS</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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ASAH1, ASN320ASP
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<br />
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SNP: rs137853596,
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ClinVar: RCV000000114
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with Farber lipogranulomatosis (FRBRL; 228000), Bar et al. (2001) described homozygosity for a 958A-G transition in the ASAH1 gene, resulting in an asn320-to-asp (N320D) substitution in the beta subunit of acid ceramidase. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 FARBER LIPOGRANULOMATOSIS</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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ASAH1, LEU182VAL
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<br />
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SNP: rs137853597,
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gnomAD: rs137853597,
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ClinVar: RCV000000115
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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 2 Indian sibs with Farber disease (FRBRL; 228000), who were born of consanguineous parents, Devi et al. (2006) identified homozygosity for a C-to-G transversion in exon 8 of the ASAH1 gene, resulting in a leu182-to-val (L182V) substitution. The parents were heterozygous for the mutation, which was not found in 101 ethnically matched controls. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY</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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ASAH1, THR42MET
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<br />
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SNP: rs145873635,
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gnomAD: rs145873635,
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ClinVar: RCV000029199, RCV000724837, RCV001270895
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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 5 children from 2 families with spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME; 159950), Zhou et al. (2012) identified a homozygous 125C-T transition in the last nucleotide of exon 2 of the ASAH1 gene, resulting in a thr42-to-met (T42M) substitution at a highly conserved residue in the alpha-subunit. The mutation was not found in 95 controls, and was found at a very low frequency (2 of 10,756 alleles) in the Exome Variant Server database. Haplotype analysis suggested a founder effect. The mutation was identified by genomewide linkage analysis followed by exome sequencing. Another patient from a third family was found to be compound heterozygous for the T42M mutation and a deletion of the ASAH1 gene (613468.0007). The T42M mutant protein was expressed in various patient tissues and showed decreased enzymatic activity (32% of controls) in in vitro functional studies, although the mutant enzyme still showed activity toward ceramide. Immunoblot experiments showed that the amount of the alpha-subunit was mildly lower than the beta subunit, suggesting that the mutation may affect the stability of the alpha-subunit and thus contribute to decreased enzyme 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">
|
|
<strong>.0007 SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ASAH1, DEL
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<br />
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ClinVar: RCV000029200
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of deletion of the ASAH1 gene that was found in compound heterozygous state in a patient with spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME; 159950) by Zhou et al. (2012), see 613468.0006. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 FARBER LIPOGRANULOMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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ASAH1, IVS11DS, A-G, +4
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<br />
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SNP: rs397509415,
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|
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ClinVar: RCV000049322
|
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with a severe form of Farber lipogranulomatosis (FRBRL; 228000) resulting in hydrops fetalis and death at age 3 days (Kattner et al., 1997), Alves et al. (2013) identified compound heterozygous mutations in the ASAH1 gene: an A-to-G transition in intron 11 (c.917+4A-G), predicted to interfere with normal splicing, and a 9.4-kb deletion encompassing exons 3 to 5 (613468.0009). Each unaffected parent was heterozygous for 1 of the mutations. Analysis of patient cells showed about 50% ASAH1 transcript compared to controls, but no detectable full-length transcript and no ASAH1 protein. The major abnormal transcript resulted from the deletion of exons 3 to 5, resulting in premature termination (Tyr42_Leu127delinsArgfsTer10). The patient's severe phenotype correlated with the 2 null ASAH1 mutations. </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>.0009 FARBER LIPOGRANULOMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
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<span class="mim-text-font">
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|
|
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ASAH1, 9.4-KB DEL
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|
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<br />
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ClinVar: RCV000656522
|
|
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|
|
|
</span>
|
|
</div>
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|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 9.4-kb deletion in the ASAH1 gene that was found in compound heterozygous state in a patient with a severe form of Farber lipogranulomatosis (FRBRL; 228000) by Alves et al. (2013), see 613468.0008. </p>
|
|
</span>
|
|
</div>
|
|
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|
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|
<div>
|
|
<br />
|
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</div>
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|
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</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ASAH1, GLY284TER
|
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|
|
<br />
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|
|
SNP: rs794729663,
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|
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|
|
ClinVar: RCV000157604
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with onset of spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME; 159950) at age 10 years, Dyment et al. (2014) identified compound heterozygous mutations in the ASAH1 gene: a c.850G-T transversion in exon 11, resulting in a gly284-to-ter (G284X) substitution, and a c.456A-C transversion (613468.0011) in exon 6, predicted to result in a lys152-to-asn (K152N) substitution; however, cDNA from patient fibroblasts showed that the latter mutation caused aberrant splicing with the skipping of exon 6. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and were filtered against the 1000 Genomes Project (2012/04 release) and Exome Variant Server (ESP6500) databases, as well as 800 in-house control exomes. Patient fibroblasts showed about 5.5% residual acid ceramidase activity and barely detectable levels of the beta subunit. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 SPINAL MUSCULAR ATROPHY WITH PROGRESSIVE MYOCLONIC EPILEPSY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ASAH1, 456A-C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs200455852,
|
|
|
|
|
|
gnomAD: rs200455852,
|
|
|
|
|
|
ClinVar: RCV000157605, RCV000853058, RCV004551355
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.456A-C mutation in the ASAH1 gene that was found in compound heterozygous state in a patient with SMAPME (159950) by Dyment et al. (2014), see 613468.0010. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 FARBER LIPOGRANULOMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ASAH1, TRP169ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs756455049,
|
|
|
|
|
|
gnomAD: rs756455049,
|
|
|
|
|
|
ClinVar: RCV000171533, RCV001728167
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Iranian sibs, aged 40, 58 and 60 years, with Farber lipogranulomatosis (FRBRL; 228000), Bonafe et al. (2016) identified compound heterozygous mutations in the ASAH1 gene: a c.505T-C transition, resulting in a trp169-to-arg (W169R) substitution, and a c.760A-G transition, resulting in an arg254-to-gly (R254G; 613468.0013) substitution. The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with disease in the family. Acid ceramidase enzyme activity in fibroblasts from 2 of the sibs was reduced to 7 to 8% of control levels. The patients had severe adult-onset peripheral osteolysis and a history of episodic fever and pain in childhood. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 FARBER LIPOGRANULOMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ASAH1, ARG254GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2117037405,
|
|
|
|
|
|
|
|
ClinVar: RCV001728066
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.760A-G transition in the ASAH1 gene, resulting in an arg254-to-gly (R254G) substitution, that was identified in compound heterozygous state in 3 Iranian sibs with lipogranulomatosis (FRBRL; 228000) by Bonafe et al. (2016), see 613468.0012. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 FARBER LIPOGRANULOMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ASAH1, CYS143GLY
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV001728066
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 25-year-old woman with Farber lipogranulomatosis (FRBRL; 228000), Bao et al. (2020) identified compound heterozygous mutations in the ASAH1 gene: a c.427T-G transversion (c.427T-G, NM_177924.3), resulting in a cys143-to-gly (C143G) substitution, and a c.358G-C transversion, resulting in an ala120-to-pro (A120P; 613468.0015) substitution. The mutations were identified by sequencing of the ASAH1 gene, and the parents were shown to be mutation carriers. The patient had osteolytic changes of the hands and toes and a history of nodules since infancy, hoarseness, joint swelling, and bone pain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 FARBER LIPOGRANULOMATOSIS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
ASAH1, ALA120PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2117047219,
|
|
|
|
|
|
|
|
ClinVar: RCV001728067
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.358G-C transversion (c.358G-C, NM_177924.3) in the ASAH1 gene, resulting in an ala120-to-pro (A120P) substitution, that was identified in compound heterozygous state in a patient with Farber lipogranulomatosis (FRBRL; 228000) by Bao et al. (2020), see 613468.0014. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ASAH1, LEU401PRO ({dbSNP rs368345612})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs368345612,
|
|
|
|
|
|
gnomAD: rs368345612,
|
|
|
|
|
|
ClinVar: RCV000515786, RCV001851128, RCV002280815
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant is classified as a variant of unknown significance because its contribution to keloid formation (KLDF; see 148100) has not been confirmed.</p><p>In a large 3-generation Nigerian Yoruba family (family A) segregating autosomal dominant keloid formation mapping to chromosome 8p23-p21, Santos-Cortez et al. (2017) identified heterozygosity for a c.1202T-C transition (c.1202T-C, NM_004315.5) in the ASAH1 gene resulting in a leu401-to-pro substitution (L401P) that was present in all 9 affected individuals as well as in 3 unaffected family members (III-10, III-12, and III-19). There were also 2 family members of unknown status, with hypertrophic or raised scars, 1 of whom (III-11) did not carry the mutation and 1 of whom (III-7) carried the haplotype but whose mutation status was not reported. Screening for the L401P variant in 318 patients with keloids identified 2 unrelated Nigerian probands with the variant. Analysis of exome variants surrounding the ASAH1 variant defined a 210.4-kb haplotype that was shared by members of family A and the 2 Nigerian probands. The L401P variant was not found in 192 unaffected Yoruba controls with no family history of keloids, but was present in 2 heterozygous African alleles (minor allele frequency, 0.00019) in the ExAC database. The authors noted that in family A, onset of keloid formation ranged from the first to the seventh decade of life; thus the 3 unaffected mutation carriers, who were under 33 years of age, might yet develop keloids. Because 2 family members developed a keloid and a normal scar at around the same age, and some family members developed keloids only at a late age, the authors hypothesized that additional factors that change over time must play a role, including environmental and/or genetic modifiers. The authors also noted that individuals heterozygous for ASAH1 variants causing Farber lipogranulomatosis (228000) or spinal muscular atrophy with progressive myoclonic epilepsy (159950) were not known to have increased risk for keloids. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
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