6091 lines
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Entry
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- *606873 - HEXOSAMINIDASE B; HEXB
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- OMIM
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<p>
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<span class="h4">*606873</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="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606873">Table View</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</h4>
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000049860;t=ENST00000261416" 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=3074" 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=606873" 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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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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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=ENSG00000049860;t=ENST00000261416" 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_000521,NM_001292004" 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_000521" 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=606873" 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="small">
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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 id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=06043&isoform_id=06043_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/HEXB" 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/179462,386770,517053,867691,16924217,21309953,32880181,55274010,119616147,119616148,209402810,258676401,308219726,635172849,1519242620,2203400814" 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/P07686" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=3074" 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=ENSG00000049860;t=ENST00000261416" 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=HEXB" 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=HEXB" 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+3074" 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/HEXB" 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:3074" 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/3074" 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=chr5&hgg_gene=ENST00000261416.12&hgg_start=74640023&hgg_end=74721288&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 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:4879" 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:4879" 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/hexb" 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=606873[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=606873[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/ENSG00000049860" 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=HEXB" 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=HEXB" 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=HEXB" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.hexdb.mcgill.ca" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=HEXB&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/PA29257" 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:4879" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0041629.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:96074" 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/HEXB#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:96074" 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/3074/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA001462/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=3074" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00020509;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-2333" 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:3074" 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=HEXB&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> 23849003<br />
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<strong>ICD10CM:</strong> E75.01<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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606873
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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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HEXOSAMINIDASE B; HEXB
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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="includedTitles" 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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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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ENC1, ANTISENSE, INCLUDED; ENC1AS, INCLUDED
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HEXB" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HEXB</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/5/253?start=-3&limit=10&highlight=253">5q13.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:74640023-74721288&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'})">5:74,640,023-74,721,288</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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</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>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/253?start=-3&limit=10&highlight=253">
|
|
5q13.3
|
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</a>
|
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</span>
|
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</td>
|
|
|
|
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<td>
|
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<span class="mim-font">
|
|
Sandhoff disease, infantile, juvenile, and adult forms
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<a href="/entry/268800"> 268800 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/606873" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<p>The HEXB gene encodes the beta subunit of the enzyme hexosaminidase (<a href="https://enzyme.expasy.org/EC/3.2.1.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 3.2.1.52</a>), which is involved in the breakdown of gangliosides. There are 2 isoenzymes of hexosaminidase: Hex-A, which is encoded by the HEXA gene (<a href="/entry/606869">606869</a>), and Hex-B. <a href="#4" class="mim-tip-reference" title="Beutler, E., Kuhl, W., Comings, D. <strong>Hexosaminidase isozyme in type O Gm2 gangliosidosis (Sandhoff-Jatzkewitz disease).</strong> Am. J. Hum. Genet. 27: 628-638, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/808963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">808963</a>]" pmid="808963">Beutler et al. (1975)</a> concluded that Hex-A has the structure alpha-beta, whereas Hex-B has the structure beta-beta. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=808963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#42" class="mim-tip-reference" title="O'Dowd, B. F., Quan, F., Willard, H. F., Lamhonwah, A.-M., Korneluk, R. G., Lowden, J. A., Gravel, R. A., Mahuran, D. J. <strong>Isolation of cDNA clones coding for the beta subunit of human beta-hexosaminidase.</strong> Proc. Nat. Acad. Sci. 82: 1184-1188, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2579389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2579389</a>] [<a href="https://doi.org/10.1073/pnas.82.4.1184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2579389">O'Dowd et al. (1985)</a> cloned a human HEXB cDNA from an SV40-transformed fibroblast cDNA library. The cDNA encodes a deduced 556-amino acid protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2579389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Bapat, B., Ethier, M., Neote, K., Mahuran D., Gravel, R. A. <strong>Cloning and sequence analysis of a cDNA encoding the beta-subunit of mouse beta-hexosaminidase.</strong> FEBS Lett. 237: 191-195, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2971567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2971567</a>] [<a href="https://doi.org/10.1016/0014-5793(88)80199-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2971567">Bapat et al. (1988)</a> cloned the murine beta subunit of hexosaminidase. The cDNA corresponded to a polypeptide of 536 amino acids, which shows 75% homology with the human peptide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2971567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#45" class="mim-tip-reference" title="Proia, R. L. <strong>Gene encoding the human beta-hexosaminidase beta chain: extensive homology of intron placement in the alpha- and beta-chain genes.</strong> Proc. Nat. Acad. Sci. 85: 1883-1887, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2964638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2964638</a>] [<a href="https://doi.org/10.1073/pnas.85.6.1883" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2964638">Proia (1988)</a> showed that the beta-chain coding region is divided into 14 exons distributed over about 40 kb of DNA. Comparison with the alpha-chain gene showed that 12 of the 13 introns interrupt the coding regions at homologous positions. This extensive sharing of intron placement demonstrates that the alpha and beta chains evolved by way of duplication of a common ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2964638" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#38" class="mim-tip-reference" title="Neote, K., Bapat, B., Dumbrille-Ross, A., Troxel, C., Schuster, S. M., Mahuran, D. J., Gravel, R. A. <strong>Characterization of the human HEXB gene encoding lysosomal beta-hexosaminidase.</strong> Genomics 3: 279-286, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2977375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2977375</a>] [<a href="https://doi.org/10.1016/0888-7543(88)90116-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2977375">Neote et al. (1988)</a> determined that the promoter region of the HEXB gene is GC-rich, with several GC boxes and a CAAT box. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2977375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#24" class="mim-tip-reference" title="Hechtman, P., Rowlands, A. <strong>Apparent hexosaminidase B deficiency in two healthy members of a pedigree.</strong> Am. J. Hum. Genet. 31: 428-438, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/484551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">484551</a>]" pmid="484551">Hechtman and Rowlands (1979)</a> studied a temperature-sensitive mutant of hexosaminidase B. <a href="#29" class="mim-tip-reference" title="Mahuran, D. J., Tsui, F., Gravel, R. A., Lowden, J. A. <strong>Evidence for two dissimilar polypeptide chains in the beta(2) subunit of hexosaminidase.</strong> Proc. Nat. Acad. Sci. 79: 1602-1605, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6951199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6951199</a>] [<a href="https://doi.org/10.1073/pnas.79.5.1602" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6951199">Mahuran et al. (1982)</a> provided biochemical evidence that the beta(2) subunit may consist of 2 dissimilar polypeptide chains: beta(a)beta(b). Genetic data suggest that these are the product of a single locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=484551+6951199" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#44" class="mim-tip-reference" title="Pennybacker, M., Liessem, B., Moczall, H., Tifft, C. J., Sandhoff, K., Proia, R. L. <strong>Identification of domains in human beta-hexosaminidase that determine substrate specificity.</strong> J. Biol. Chem. 271: 17377-17382, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663217</a>] [<a href="https://doi.org/10.1074/jbc.271.29.17377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8663217">Pennybacker et al. (1996)</a> identified domains in human hexosaminidase that confer distinctive substrate specificity to Hex-A (composed of alpha-beta chains), Hex-B (beta-beta), and Hex-S (alpha-alpha) isozymes. The active site on the beta subunit primarily degrades neutral substrates while the alpha-subunit site is active against sulfated substrates. Only Hex-A, together with the GM2 activator protein, can degrade GM2 ganglioside. <a href="#44" class="mim-tip-reference" title="Pennybacker, M., Liessem, B., Moczall, H., Tifft, C. J., Sandhoff, K., Proia, R. L. <strong>Identification of domains in human beta-hexosaminidase that determine substrate specificity.</strong> J. Biol. Chem. 271: 17377-17382, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663217</a>] [<a href="https://doi.org/10.1074/jbc.271.29.17377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8663217">Pennybacker et al. (1996)</a> generated chimeric hexosaminidase subunits by interchanging analogous regions of the alpha and beta subunits. Chimeric constructs were expressed in HeLa cells and selected constructs were produced in the baculovirus expression system to determine their ability to degrade GM2 ganglioside in the presence of GM2 activator protein. Their results allowed them to define 2 noncontiguous sequences in the alpha subunit (amino acids 1-191 and 403-529) which, when substituted into analogous positions in the beta subunit, conferred activity against the sulfated substrate. <a href="#44" class="mim-tip-reference" title="Pennybacker, M., Liessem, B., Moczall, H., Tifft, C. J., Sandhoff, K., Proia, R. L. <strong>Identification of domains in human beta-hexosaminidase that determine substrate specificity.</strong> J. Biol. Chem. 271: 17377-17382, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8663217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8663217</a>] [<a href="https://doi.org/10.1074/jbc.271.29.17377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8663217">Pennybacker et al. (1996)</a> also found that amino acids 225-556 in the beta subunit are required for activator-dependent GM2 ganglioside degradation by HEXA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8663217" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Alterations in chromosome 5q13 are a frequent finding in hairy cell leukemia (HCL). <a href="#22" class="mim-tip-reference" title="Hammarsund, M., Lerner, M., Zhu, C., Merup, M., Jansson, M., Gahrton, G., Kluin-Nelemans, H., Einhorn, S., Grander, D., Sangfelt, O., Corcoran, M. <strong>Disruption of a novel ectodermal neural cortex 1 antisense gene, ENC-1AS and identification of ENC-1 overexpression in hairy cell leukemia.</strong> Hum. Molec. Genet. 13: 2925-2936, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15459180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15459180</a>] [<a href="https://doi.org/10.1093/hmg/ddh315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15459180">Hammarsund et al. (2004)</a> reported that a 5q13.3 breakpoint discovered in an HCL patient disrupted a conserved alternative isoform of HEXB. This isoform directly overlapped, in a cis-antisense fashion, exon 1 of ENC1 (<a href="/entry/605173">605173</a>), and was thus named ENC1AS. Purified HCL tumor cells from 26 HCL patients showed striking upregulation of ENC1 in all 26 samples analyzed. <a href="#22" class="mim-tip-reference" title="Hammarsund, M., Lerner, M., Zhu, C., Merup, M., Jansson, M., Gahrton, G., Kluin-Nelemans, H., Einhorn, S., Grander, D., Sangfelt, O., Corcoran, M. <strong>Disruption of a novel ectodermal neural cortex 1 antisense gene, ENC-1AS and identification of ENC-1 overexpression in hairy cell leukemia.</strong> Hum. Molec. Genet. 13: 2925-2936, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15459180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15459180</a>] [<a href="https://doi.org/10.1093/hmg/ddh315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15459180">Hammarsund et al. (2004)</a> identified a complex 5-prime regulatory mechanism involving an inverse expression of the ENC1 and the ENC1AS transcripts in several tissues, suggesting that expression of ENC1AS may regulate ENC1 levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15459180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 RNA interference to deplete host genes in Mycobacterium marinum (Mm)-infected Drosophila S2 cells, which share properties with mammalian macrophages, <a href="#28" class="mim-tip-reference" title="Koo, I. C., Ohol, Y. M., Wu, P., Morisaki, J. H., Cox, J. S., Brown, E. J. <strong>Role of lysosomal enzyme beta-hexosaminidase in the control of mycobacteria infection.</strong> Proc. Nat. Acad. Sci. 105: 710-715, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18180457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18180457</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18180457[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0708110105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18180457">Koo et al. (2008)</a> identified a mycobactericidal role for Hexb. They confirmed the importance of mammalian Hexb in controlling Mm growth using macrophages from Hexb -/- mice. Treatment of Hexb -/- mouse cells with Ifng (<a href="/entry/147570">147570</a>) abolished their susceptibility to Mm. Exposure of mouse macrophages to Mm, with or without phagocytosis, induced Hexb secretion, suggesting that Mm comes into contact with Hexb at the plasma membrane. Incubation of Mm with Hexb, at neutral or acidic pH, killed Mm. <a href="#28" class="mim-tip-reference" title="Koo, I. C., Ohol, Y. M., Wu, P., Morisaki, J. H., Cox, J. S., Brown, E. J. <strong>Role of lysosomal enzyme beta-hexosaminidase in the control of mycobacteria infection.</strong> Proc. Nat. Acad. Sci. 105: 710-715, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18180457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18180457</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18180457[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0708110105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18180457">Koo et al. (2008)</a> concluded that HEXB is a peptidoglycan hydrolase and proposed that it is involved in restricting mycobacteria growth even before the onset of adaptive immunity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18180457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The HEXB locus has been assigned to chromosome 5 (<a href="#20" class="mim-tip-reference" title="Gilbert, F., Kucherlapati, R. S., Creagan, R. P., Murnane, M. J., Darlington, G. J., Ruddle, F. H. <strong>Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes.</strong> Proc. Nat. Acad. Sci. 72: 263-267, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1054503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1054503</a>] [<a href="https://doi.org/10.1073/pnas.72.1.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1054503">Gilbert et al., 1975</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1054503" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Various Sandhoff strains, even cells from the infantile and the rare juvenile forms, fail to complement in heterokaryons, suggesting that these are the result of allelic mutations in the beta subunit of HEXB. <a href="#12" class="mim-tip-reference" title="Dana, S., Wasmuth, J. J. <strong>Selective linkage disruption in human-Chinese hamster cell hybrids: deletion mapping of the leuS, hexB, emtB, and chr genes on human chromosome 5.</strong> Molec. Cell. Biol. 2: 1220-1228, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7177110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7177110</a>] [<a href="https://doi.org/10.1128/mcb.2.10.1220-1228.1982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7177110">Dana and Wasmuth (1982)</a> did cytogenetic and biochemical analyses of spontaneous segregants from Chinese hamster-human interspecific hybrid cells (which contained human chromosome 5 and expressed the 4 syntenic genes LEUS, HEXB, EMTB, and CHR), the hybrid cell being subjected to selective conditions requiring them to retain the LEUS gene. From these analyses, <a href="#12" class="mim-tip-reference" title="Dana, S., Wasmuth, J. J. <strong>Selective linkage disruption in human-Chinese hamster cell hybrids: deletion mapping of the leuS, hexB, emtB, and chr genes on human chromosome 5.</strong> Molec. Cell. Biol. 2: 1220-1228, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7177110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7177110</a>] [<a href="https://doi.org/10.1128/mcb.2.10.1220-1228.1982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7177110">Dana and Wasmuth (1982)</a> concluded that the order is as listed above and that the specific locations are: LEUS, 5pter-q1; HEXB, 5q13; EMTB, 5q23-q35; CHR, 5q35. In a child with a de novo balanced translocation t(5;13)(q11;p11), <a href="#32" class="mim-tip-reference" title="Mattei, J. F., Balestrazzi, P., Baeteman, M. A., Mattei, M. G. <strong>De novo balanced translocation (5;13)(q11;p11) in a child with Franceschetti syndrome and significant decrease of hexosaminidase B. (Abstract)</strong> Cytogenet. Cell Genet. 37: 532, 1984."None>Mattei et al. (1984)</a> found decreased levels of Hex-B, suggesting to these workers that the HEXB gene assignment can be narrowed to 5q11. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7177110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Killary, A. M., Leach, R. J., Moran, R. G., Fournier, R. E. K. <strong>Assignment of the genes encoding dihydrofolate reductase and hexosaminidase B to mouse chromosome 13. (Abstract)</strong> Am. J. Hum. Genet. 39: A159, 1986."None>Killary et al. (1986)</a> assigned the HEXB locus to mouse chromosome 13 by study of mouse-hamster hybrids.</p>
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<p><a href="#41" class="mim-tip-reference" title="O'Brien, J. S. <strong>Suggestions for a nomenclature for the GM2 gangliosidoses making certain (possibly unwarranted) assumptions. (Comments)</strong> Am. J. Hum. Genet. 30: 672-675, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/747190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">747190</a>]" pmid="747190">O'Brien (1978)</a> made suggestions for the nomenclature of alleles at the HEX alpha and beta loci. The alleles at the beta locus in his system are numbered as follows: 1--wildtype; 2--Sandhoff; 3--normal with deficient Hex-A and Hex-B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=747190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Bikker, H., van den Berg, F. M., Wolterman, R. A., de Vijlder, J. J. M., Bolhuis, P. A. <strong>Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis.</strong> Hum. Genet. 81: 287-288, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2921040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2921040</a>] [<a href="https://doi.org/10.1007/BF00279006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2921040">Bikker et al. (1989)</a> demonstrated a 16-kb deletion in 1 allele of the HEXB gene (<a href="#0001">606873.0001</a>) in 2 apparently unrelated patients with Sandhoff disease (<a href="/entry/268800">268800</a>) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2921040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Oonk, J. G. W., Van der Helm, H. J., Martin, J. J. <strong>Spinocerebellar degeneration: hexosaminidase A and B deficiency in two adult sisters.</strong> Neurology 29: 380-384, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/571983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">571983</a>] [<a href="https://doi.org/10.1212/wnl.29.3.380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="571983">Oonk et al. (1979)</a> reported the cases of 2 adult sisters with spinocerebellar degeneration and very low activities of both Hex-A and Hex-B. <a href="#8" class="mim-tip-reference" title="Bolhuis, P. A., Oonk, J. G. W., Kamp, P. E., Ris, A. J., Michalski, J. C., Overdijk, B., Reuser, A. J. J. <strong>Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease.</strong> Neurology 37: 75-81, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2948136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2948136</a>] [<a href="https://doi.org/10.1212/wnl.37.1.75" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2948136">Bolhuis et al. (1987)</a> concluded that the disorder was the result of a 'destabilizing mutation' in the HEXB locus. <a href="#9" class="mim-tip-reference" title="Bolhuis, P. A., Ponne, N. J., Bikker, H., Baas, F., de Jong, J. M. B. V. <strong>Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.</strong> Biochim. Biophys. Acta 1182: 142-146, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8357844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8357844</a>] [<a href="https://doi.org/10.1016/0925-4439(93)90134-m" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8357844">Bolhuis et al. (1993)</a> demonstrated that these 2 sisters were compound heterozygotes for an mRNA-negative allele on 1 chromosome 5 and an R505Q mutation (<a href="#0009">606873.0009</a>) on the homologous chromosome. Transfection of COS cells with a cDNA construct containing the R505Q mutation resulted in the expression of a labile form of beta-hexosaminidase, thus confirming their earlier conclusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=571983+8357844+2948136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#40" class="mim-tip-reference" title="Neufeld, E. F. <strong>Natural history and inherited disorders of a lysosomal enzyme, beta-hexosaminidase.</strong> J. Biol. Chem. 264: 10927-10930, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2525553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2525553</a>]" pmid="2525553">Neufeld (1989)</a> provided a review of the disorders related to mutations in the HEXA and HEXB genes. <a href="#31" class="mim-tip-reference" title="Mahuran, D. <strong>Personal Communication.</strong> Toronto, Canada 9/17/1998."None>Mahuran (1998)</a> stated that he maintains a database of published hexosaminidase and GM2A (<a href="/entry/613109">613109</a>) mutations and that the database contains 23 HEXB mutations, 86 HEXA (<a href="/entry/606869">606869</a>) mutations, and 4 GM2A mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2525553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 12 unrelated Italian patients with Sandhoff disease, 11 of whom had the infantile type, <a href="#52" class="mim-tip-reference" title="Zampieri, S., Filocamo, M., Buratti, E., Stroppiano, M., Vlahovicek, K., Rosso, N., Bignulin, E., Regis, S., Carnevale, F., Bembi, B., Dardis, A. <strong>Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles.</strong> Neurogenetics 10: 49-58, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18758829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18758829</a>] [<a href="https://doi.org/10.1007/s10048-008-0145-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18758829">Zampieri et al. (2009)</a> identified 11 different mutations in the HEXB gene, including 6 novel mutations (see, e.g., <a href="#0017">606873.0017</a> and <a href="#0018">606873.0018</a>). The common 16-kb deletion (<a href="#0001">606873.0001</a>) was not identified in this patient cohort. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18758829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs with adult-type Sandhoff disease, <a href="#48" class="mim-tip-reference" title="Santoro, M., Modoni, A., Sabatelli, M., Madia, F., Piemonte, F., Tozzi, G., Ricci, E., Tonali, P. A., Silvestri, G. <strong>Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect.</strong> Molec. Genet. Metab. 91: 111-114, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17251047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17251047</a>] [<a href="https://doi.org/10.1016/j.ymgme.2006.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17251047">Santoro et al. (2007)</a> identified homozygosity for a missense mutation in the HEXB gene (D494G; <a href="#0019">606873.0019</a>). Leukocyte enzyme analysis showed reduced total Hex activity, absent Hex-B activity, and normal Hex-A activity. The mutation segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17251047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>19 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606873[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<p>By field inversion gel electrophoresis (FIGE) of SfiI-digested chromosomal DNA, <a href="#5" class="mim-tip-reference" title="Bikker, H., van den Berg, F. M., Wolterman, R. A., de Vijlder, J. J. M., Bolhuis, P. A. <strong>Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis.</strong> Hum. Genet. 81: 287-288, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2921040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2921040</a>] [<a href="https://doi.org/10.1007/BF00279006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2921040">Bikker et al. (1989)</a> demonstrated a 16-kb deletion in 1 allele of the HEXB gene in 2 apparently unrelated patients with Sandhoff disease (<a href="/entry/268800">268800</a>). <a href="#30" class="mim-tip-reference" title="Mahuran, D. J. <strong>Personal Communication.</strong> Toronto, Ontario, Canada 12/1/1994."None>Mahuran (1994)</a> pointed out that the 50-kb deletion (50-KB DEL) originally reported by <a href="#5" class="mim-tip-reference" title="Bikker, H., van den Berg, F. M., Wolterman, R. A., de Vijlder, J. J. M., Bolhuis, P. A. <strong>Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis.</strong> Hum. Genet. 81: 287-288, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2921040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2921040</a>] [<a href="https://doi.org/10.1007/BF00279006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2921040">Bikker et al. (1989)</a> is the same as the 16-kb deletion described by <a href="#39" class="mim-tip-reference" title="Neote, K., McInnes, B., Mahuran, D. J., Gravel, R. A. <strong>Structure and distribution of an Alu-type deletion mutation in Sandhoff disease.</strong> J. Clin. Invest. 86: 1524-1531, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2147027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2147027</a>] [<a href="https://doi.org/10.1172/JCI114871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2147027">Neote et al. (1990)</a>. The size was incorrectly estimated by <a href="#5" class="mim-tip-reference" title="Bikker, H., van den Berg, F. M., Wolterman, R. A., de Vijlder, J. J. M., Bolhuis, P. A. <strong>Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis.</strong> Hum. Genet. 81: 287-288, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2921040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2921040</a>] [<a href="https://doi.org/10.1007/BF00279006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2921040">Bikker et al. (1989)</a>; see <a href="#7" class="mim-tip-reference" title="Bolhuis, P. A., Bikker, H. <strong>Deletion of the 5-prime-region in one or two alleles of HEXB in 15 out of 30 patients with Sandhoff disease (Letter)</strong> Hum. Genet. 90: 328-329, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1487253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1487253</a>] [<a href="https://doi.org/10.1007/BF00220096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1487253">Bolhuis and Bikker (1992)</a>. In conventional Southern blot analysis, this deletion was masked by hybridization of bands from the other allele. Among 14 patients with Sandhoff disease from different parts of Europe, <a href="#6" class="mim-tip-reference" title="Bikker, H., van den Berg, F. M., Wolterman, R. A., Kleijer, W. J., de Vijlder, J. J. M., Bolhuis, P. A. <strong>Distribution and characterization of a Sandhoff disease-associated 50-kb deletion in the gene encoding the human beta-hexosaminidase beta-chain.</strong> Hum. Genet. 85: 327-329, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1975561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1975561</a>] [<a href="https://doi.org/10.1007/BF00206756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1975561">Bikker et al. (1990)</a> found homozygosity for the deletion in 2 and heterozygosity in 7. It appeared that the deletion started in intron 5, extending in the 5-prime direction and causing the loss of exons 1 to 5 and the promoter area of the HEXB gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1975561+1487253+2147027+2921040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DNA from fibroblasts of a patient with the infantile form of Sandhoff disease, <a href="#39" class="mim-tip-reference" title="Neote, K., McInnes, B., Mahuran, D. J., Gravel, R. A. <strong>Structure and distribution of an Alu-type deletion mutation in Sandhoff disease.</strong> J. Clin. Invest. 86: 1524-1531, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2147027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2147027</a>] [<a href="https://doi.org/10.1172/JCI114871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2147027">Neote et al. (1990)</a> identified a deletion of approximately 16 kb, including the HEXB promoter, exons 1 through 5, and part of intron 5. The deletion probably arose from recombination between 2 Alu sequences, with the breakpoints occurring at the midpoint between the left and right arms in each case and regenerating an intact Alu element in the deletion sequence. The deletion allele accounted for 8 of 30 Sandhoff mutant alleles analyzed. It was present in homozygous state in 2 cell lines from patients with the infantile form, in heterozygous form together with an intron 12 deletion in a juvenile case, and in heterozygous form in 2 adult Sandhoff cases. The last 3 cases plus 1 infantile case had the Alu-type deletion in compound heterozygous (i.e., heteroallelic) state (see <a href="#0014">606873.0014</a>). <a href="#33" class="mim-tip-reference" title="McInnes, B., Potier, M., Wakamatsu, N., Melancon, S. B., Klavins, M. H., Tsuji, S., Mahuran, D. J. <strong>An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds.</strong> J. Clin. Invest. 90: 306-314, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1386607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1386607</a>] [<a href="https://doi.org/10.1172/JCI115863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1386607">McInnes et al. (1992)</a> reported that this 16-kb deletion accounted for 27% of the Sandhoff alleles they analyzed. This null allele was associated with the juvenile pro417-to-leu mutation (<a href="#0007">606873.0007</a>) which interfered with the normal acceptor splice site. This combination in a French Canadian family was accompanied by a very mild phenotype which <a href="#33" class="mim-tip-reference" title="McInnes, B., Potier, M., Wakamatsu, N., Melancon, S. B., Klavins, M. H., Tsuji, S., Mahuran, D. J. <strong>An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds.</strong> J. Clin. Invest. 90: 306-314, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1386607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1386607</a>] [<a href="https://doi.org/10.1172/JCI115863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1386607">McInnes et al. (1992)</a> attributed to differences in racial background. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1386607+2147027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 SANDHOFF DISEASE, JUVENILE TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs201580118 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201580118;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/rs201580118?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=rs201580118" 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=rs201580118" 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=RCV000633008 OR RCV002286417 OR RCV002529814 OR RCV003153772" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000633008, RCV002286417, RCV002529814, RCV003153772" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000633008...</a>
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<p>In a case of the juvenile form of Sandhoff disease (<a href="/entry/268800">268800</a>) reported by <a href="#51" class="mim-tip-reference" title="Wood, S., MacDougall, B. G. <strong>Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts.</strong> Am. J. Hum. Genet. 28: 489-495, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10724</a>]" pmid="10724">Wood and MacDougall (1976)</a>, <a href="#34" class="mim-tip-reference" title="Nakano, T., Suzuki, K. <strong>Genetic cause of a juvenile form of Sandhoff disease: abnormal splicing of beta-hexosaminidase beta chain gene transcript due to a point mutation within intron 12.</strong> J. Biol. Chem. 264: 5155-5158, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2522450/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2522450</a>]" pmid="2522450">Nakano and Suzuki (1989)</a> showed that a cDNA clone isolated from fibroblasts contained an extra 24-base segment between exons 12 and 13. This segment was identified as the 3-prime terminus of intron 12. The remainder of the coding sequence was completely normal. The insertion was 'in frame' and added 8 amino acids between amino acids 491 and 492 of the enzyme protein. It was located only 5 amino acids away from a possible glycosylation site. Gene amplification by the PCR and subsequent sequencing of genomic DNA showed that the patient was a compound heterozygote. In 1 allele there was a single nucleotide transition from normal G to A at 26 bases from the 3-prime terminus of intron 12. This mutation generated a consensus sequence for the 3-prime splice site for an intron and thus explained the abnormal mRNAs that retain 24 bases of the 3-prime terminus of intron 12. The intron 12 and flanking exons 12 and 13 sequences were normal in the other allele. The other mutant allele was thought to be of an mRNA-negative type. The same mutation was found in a 35-year-old Japanese man with manifestations of juvenile Sandhoff disease: progressive neurogenic muscular atrophy, cerebellar ataxia, and mental deterioration beginning at age 10. <a href="#13" class="mim-tip-reference" title="Dlott, B., d'Azzo, A., Quon, D. V. K., Neufeld, E. F. <strong>Two mutations produce intron insertion in mRNA and elongated beta-subunit of human beta-hexosaminidase.</strong> J. Biol. Chem. 265: 17921-17927, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2170400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2170400</a>]" pmid="2170400">Dlott et al. (1990)</a> found the same mutation in cells from 2 juvenile Sandhoff disease patients and a third, asymptomatic individual. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10724+2170400+2522450" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 HEXOSAMINIDASE B (PARIS)</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">rs1554037309 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554037309;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=rs1554037309" 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=rs1554037309" 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=RCV000596163 OR RCV000674261 OR RCV002286414" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000596163, RCV000674261, RCV002286414" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000596163...</a>
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<p><a href="#14" class="mim-tip-reference" title="Dreyfus, J. C., Poenaru, L., Vibert, M., Ravise, N., Boue, J. <strong>Characterization of a variant of beta-hexosaminidase: 'hexosaminidase Paris.'.</strong> Am. J. Hum. Genet. 29: 287-293, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/868875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">868875</a>]" pmid="868875">Dreyfus et al. (1977)</a> characterized a hexosaminidase variant that may represent unstable beta subunits. <a href="#13" class="mim-tip-reference" title="Dlott, B., d'Azzo, A., Quon, D. V. K., Neufeld, E. F. <strong>Two mutations produce intron insertion in mRNA and elongated beta-subunit of human beta-hexosaminidase.</strong> J. Biol. Chem. 265: 17921-17927, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2170400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2170400</a>]" pmid="2170400">Dlott et al. (1990)</a> demonstrated that this so-called 'hexosaminidase Paris' had an abnormally elongated beta subunit due to duplication of a region straddling the junction of intron 13 and exon 14, which generated an alternate splice site and caused an in-frame insertion of 18 nucleotides into the mRNA. The normal splice site seemed to be used to some extent, accounting for the residual Hex-A isoenzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2170400+868875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MOVED TO <a href="/entry/606873#0001">606873.0001</a></strong>
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<strong>.0005 HEXB POLYMORPHISM</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs10805890 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10805890;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/rs10805890?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=rs10805890" 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=rs10805890" 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=RCV000079065 OR RCV000235014 OR RCV000403428 OR RCV000675619" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000079065, RCV000235014, RCV000403428, RCV000675619" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000079065...</a>
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<p>The ile207-to-val substitution was found to be a common polymorphism by <a href="#53" class="mim-tip-reference" title="Zhang, Z.-X., Wakamatsu, N., Akerman, B. R., Mules, E. H., Thomas, G. H., Gravel, R. A. <strong>A second, large deletion in the HEXB gene in a patient with infantile Sandhoff disease.</strong> Hum. Molec. Genet. 4: 777-780, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7633435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7633435</a>] [<a href="https://doi.org/10.1093/hmg/4.4.777" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7633435">Zhang et al. (1995)</a> and <a href="#46" class="mim-tip-reference" title="Redonnet-Vernhet, I., Mahuran, D. J., Salvayre, R., Dubas, F., Levade, T. <strong>Significance of two point mutations present in each HEXB allele of patients with adult G-M2 gangliosidosis (Sandhoff disease): homozygosity for the ile207-to-val substitution is not associated with a clinical or biochemical phenotype.</strong> Biochim. Biophys. Acta 1317: 127-133, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8950198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8950198</a>] [<a href="https://doi.org/10.1016/s0925-4439(96)00044-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8950198">Redonnet-Vernhet et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8950198+7633435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 SANDHOFF DISEASE, JUVENILE TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121907982 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907982;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/rs121907982?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=rs121907982" 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=rs121907982" 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=RCV000004081 OR RCV000675054 OR RCV001553740 OR RCV004719618" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004081, RCV000675054, RCV001553740, RCV004719618" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004081...</a>
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<p>In a female patient with juvenile onset of Sandhoff disease (<a href="/entry/268800">268800</a>) manifest as a motor neuron disease (<a href="#10" class="mim-tip-reference" title="Cashman, N. R., Antel, J. P., Hancock, L. W., Dawson, G., Horwitz, A. L., Johnson, W. G., Huttenlocher, P. R., Wollmann, R. L. <strong>N-acetyl-beta-hexosaminidase beta locus defect and juvenile motor neuron disease: a case study.</strong> Ann. Neurol. 19: 568-572, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3014997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3014997</a>] [<a href="https://doi.org/10.1002/ana.410190608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3014997">Cashman et al., 1986</a>), <a href="#2" class="mim-tip-reference" title="Banerjee, P., Siciliano, L., Oliveri, D., McCabe, N. R., Boyers, M. J., Horwitz, A. L., Li, S.-C., Dawson, G. <strong>Molecular basis of an adult form of beta-hexosaminidase B deficiency with motor neuron disease.</strong> Biochem. Biophys. Res. Commun. 181: 108-115, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1720305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1720305</a>] [<a href="https://doi.org/10.1016/s0006-291x(05)81388-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1720305">Banerjee et al. (1991)</a> found a heterozygous 1367A-C transversion in the HEXB gene, resulting in a tyr456-to-ser (Y456S) substitution derived from the maternal allele. The patient was also heterozygous for 2 polymorphisms: a 619A-G transition resulting in an ile207-to-val (I207V) substitution from the paternal allele, and K121R (<a href="#0008">606873.0008</a>). The patient had progressive motor neuron disease that began at age 7 and was characterized by dysarthria, muscle wasting, fasciculations, and pyramidal tract dysfunction. Rectal biopsy at age 24 showed membranous cytoplasmic bodies in submucosal ganglion cells. Biochemical studies showed partial HexA (30-50% of controls) with absence of HexB. The unaffected mother also had partial HexA and partial HexB deficiency. In vitro functional expression studies by <a href="#1" class="mim-tip-reference" title="Banerjee, P., Boyers, M. J., Berry-Kravis, E., Dawson, G. <strong>Preferential beta-hexosaminidase (Hex) A (alpha-beta) formation in the absence of beta-Hex B (beta-beta) due to heterozygous point mutations present in beta-Hex beta-chain alleles of a motor neuron disease patient.</strong> J. Biol. Chem. 269: 4819-4826, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8106452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8106452</a>]" pmid="8106452">Banerjee et al. (1994)</a> showed that the Y456S variant was completely nonfunctional and was predicted to interfere with formation of a functional dimer. <a href="#1" class="mim-tip-reference" title="Banerjee, P., Boyers, M. J., Berry-Kravis, E., Dawson, G. <strong>Preferential beta-hexosaminidase (Hex) A (alpha-beta) formation in the absence of beta-Hex B (beta-beta) due to heterozygous point mutations present in beta-Hex beta-chain alleles of a motor neuron disease patient.</strong> J. Biol. Chem. 269: 4819-4826, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8106452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8106452</a>]" pmid="8106452">Banerjee et al. (1994)</a> proposed that the variant I207V beta-chain inherited from the father must undergo preferential association with the normal alpha-chains in the patient, thus producing only HexA. Further studies indicated that the I207V beta-chain does not self-associate at low concentrations. Thus, in a patient with a nonfunctional HEXB allele, the effective concentration of beta-chains is reduced to 50% of normal, and the remaining I207V chains fail to self-associate to form HexB, but can still dimerize with the abundant normal alpha-chains, thus producing partial beta-Hex A and no beta-Hex B. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3014997+1720305+8106452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 SANDHOFF DISEASE, JUVENILE TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28942073 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28942073;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/rs28942073?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=rs28942073" 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=rs28942073" 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=RCV000004082 OR RCV000004084 OR RCV000079058 OR RCV000174009 OR RCV002251870 OR RCV003407272 OR RCV004018549" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004082, RCV000004084, RCV000079058, RCV000174009, RCV002251870, RCV003407272, RCV004018549" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004082...</a>
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<p><a href="#50" class="mim-tip-reference" title="Wakamatsu, N., Kobayashi, H., Miyatake, T., Tsuji, S. <strong>A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3-prime splice site selection.</strong> J. Biol. Chem. 267: 2406-2413, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1531140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1531140</a>]" pmid="1531140">Wakamatsu et al. (1992)</a> studied a 39-year-old Japanese male with a mild clinical presentation of mental retardation and 'local panatrophy.' The parents were first cousins. HEXB activity was undetectable in the patient's leukocytes and fibroblasts and HEXA activity was decreased to 6 and 8% of control values, respectively. Rectal biopsy demonstrated membranous cytoplasmic bodies in neurons of Meissner plexus. The urine contained large amounts of neutral oligosaccharides. <a href="#50" class="mim-tip-reference" title="Wakamatsu, N., Kobayashi, H., Miyatake, T., Tsuji, S. <strong>A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3-prime splice site selection.</strong> J. Biol. Chem. 267: 2406-2413, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1531140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1531140</a>]" pmid="1531140">Wakamatsu et al. (1992)</a> discovered a novel exon mutation affecting 3-prime splice site selection. Nucleotide sequence analysis of the HEXB gene showed 2 single base substitutions, one in exon 2 (A to G, a known polymorphism) and the other in exon 11 (C to T). Analysis of the beta-subunit mRNA demonstrated activation of a cryptic splice site in exon 11 as well as skipping of the exon. A transfection assay using a chimeric gene containing intron 10 flanked by cDNA sequences carrying the mutation confirmed that the single base substitution located at position 8 of exon 11 inhibited the selection of the normal 3-prime splice site. The CCG-to-CTG mutation resulted in substitution of leucine for proline-417 in exon 11. The mutation was present in homozygous state in the patient and in heterozygous state in the parents and a sister. Its effect was to abolish an MspI site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1531140" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#33" class="mim-tip-reference" title="McInnes, B., Potier, M., Wakamatsu, N., Melancon, S. B., Klavins, M. H., Tsuji, S., Mahuran, D. J. <strong>An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds.</strong> J. Clin. Invest. 90: 306-314, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1386607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1386607</a>] [<a href="https://doi.org/10.1172/JCI115863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1386607">McInnes et al. (1992)</a> described a 57-year-old man with very mild manifestations of Sandhoff disease (<a href="/entry/268800">268800</a>) although his genotype and low residual enzyme activity were considered predictive of the much more severe juvenile Sandhoff disease. They demonstrated that the patient was a genetic compound of the infantile 5-prime deletion mutation described by <a href="#39" class="mim-tip-reference" title="Neote, K., McInnes, B., Mahuran, D. J., Gravel, R. A. <strong>Structure and distribution of an Alu-type deletion mutation in Sandhoff disease.</strong> J. Clin. Invest. 86: 1524-1531, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2147027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2147027</a>] [<a href="https://doi.org/10.1172/JCI114871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2147027">Neote et al. (1990)</a>, a null mutation (<a href="#0001">606873.0001</a>), and the juvenile intron 10/exon 11 C-to-T mutation. Of his 6 clinically unaffected sibs, 4 of them, ranging in age from 51 to 62 years, were also genetic compounds for the same 2 Sandhoff alleles. The variable phenotype associated with the intron 10/exon 11 C-to-T transition indicates that other unidentified factors determine the pathologic outcome of the mutation. Genetic variations in the RNA splicing machinery may be the explanation. The patient, a French Canadian, had had severe watery diarrhea over a 9-year period with intermittent moderate and diffuse abdominal pain, a 17-kg weight loss over a 7-year period, and increasing weakness. Physical examination showed lower limb hyperreflexia and impaired thermal sensitivity of legs and arms. Intolerance to warm weather due to impaired sweating, impaired sexual function progressing to complete impotence, mild urinary incontinence, and orthostatic hypotension were noted. One of the sisters, aged 58, had complained of diarrhea for 10 years and postural dizziness for 5 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1386607+2147027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 HEXB POLYMORPHISM</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs11556045 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11556045;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/rs11556045?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=rs11556045" 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=rs11556045" 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=RCV000004078 OR RCV000079063 OR RCV000336190 OR RCV000675618" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004078, RCV000079063, RCV000336190, RCV000675618" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004078...</a>
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<p>In the course of studying a case of juvenile Sandhoff disease (<a href="/entry/268800">268800</a>), <a href="#50" class="mim-tip-reference" title="Wakamatsu, N., Kobayashi, H., Miyatake, T., Tsuji, S. <strong>A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3-prime splice site selection.</strong> J. Biol. Chem. 267: 2406-2413, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1531140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1531140</a>]" pmid="1531140">Wakamatsu et al. (1992)</a> found the AAA-to-AGA polymorphism in exon 2, which results in alternative substitution of arginine for lysine-121. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1531140" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs121907983 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907983;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/rs121907983?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=rs121907983" 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=rs121907983" 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=RCV000004083 OR RCV000669552" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004083, RCV000669552" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004083...</a>
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<p>In 2 sisters with adult Sandhoff disease (<a href="/entry/268800">268800</a>) presenting as spinocerebellar degeneration, reported by <a href="#43" class="mim-tip-reference" title="Oonk, J. G. W., Van der Helm, H. J., Martin, J. J. <strong>Spinocerebellar degeneration: hexosaminidase A and B deficiency in two adult sisters.</strong> Neurology 29: 380-384, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/571983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">571983</a>] [<a href="https://doi.org/10.1212/wnl.29.3.380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="571983">Oonk et al. (1979)</a> and previously studied by <a href="#8" class="mim-tip-reference" title="Bolhuis, P. A., Oonk, J. G. W., Kamp, P. E., Ris, A. J., Michalski, J. C., Overdijk, B., Reuser, A. J. J. <strong>Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease.</strong> Neurology 37: 75-81, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2948136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2948136</a>] [<a href="https://doi.org/10.1212/wnl.37.1.75" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2948136">Bolhuis et al. (1987)</a>, <a href="#9" class="mim-tip-reference" title="Bolhuis, P. A., Ponne, N. J., Bikker, H., Baas, F., de Jong, J. M. B. V. <strong>Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.</strong> Biochim. Biophys. Acta 1182: 142-146, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8357844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8357844</a>] [<a href="https://doi.org/10.1016/0925-4439(93)90134-m" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8357844">Bolhuis et al. (1993)</a> found that the HEXB gene contained a G-to-A transition at nucleotide position 1514, resulting in a change in the electric charge at amino acid position 505 by substitution of glutamine for arginine in a highly conserved part of the beta chain. The nucleotide transition generated a new restriction site for DdeI, which was present in only 1 of the alleles. <a href="#9" class="mim-tip-reference" title="Bolhuis, P. A., Ponne, N. J., Bikker, H., Baas, F., de Jong, J. M. B. V. <strong>Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.</strong> Biochim. Biophys. Acta 1182: 142-146, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8357844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8357844</a>] [<a href="https://doi.org/10.1016/0925-4439(93)90134-m" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8357844">Bolhuis et al. (1993)</a> demonstrated that the second allele was of mRNA-negative type. Thus, the patient was a genetic compound. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=571983+8357844+2948136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 SANDHOFF DISEASE, ADULT TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28942073 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28942073;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/rs28942073?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=rs28942073" 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=rs28942073" 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=RCV000004082 OR RCV000004084 OR RCV000079058 OR RCV000174009 OR RCV002251870 OR RCV003407272 OR RCV004018549" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004082, RCV000004084, RCV000079058, RCV000174009, RCV002251870, RCV003407272, RCV004018549" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004082...</a>
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<p>In a 35-year-old man who was evaluated at age 30 years because of slowly progressive lower limb weakness and diffuse fasciculations, <a href="#21" class="mim-tip-reference" title="Gomez-Lira, M., Sangalli, A., Mottes, M., Perusi, C., Pignatti, P. F., Rizzuto, N., Salviati, A. <strong>A common beta hexosaminidase gene mutation in adult Sandhoff disease patients.</strong> Hum. Genet. 96: 417-422, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7557963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7557963</a>] [<a href="https://doi.org/10.1007/BF00191799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7557963">Gomez-Lira et al. (1995)</a> found compound heterozygosity with a common deletion at the 5-prime end of the HEXB gene and a C-to-T transition at nucleotide 1214, resulting in a pro405-to-leu amino acid substitution in the gene product. The patient was an executive secretary and had been a rock climber until age 29 years, when lower limb weakness began. On neurologic examination, moderate reduction in strength, widespread spontaneous fasciculations, and hyperactive deep tendon reflexes were observed. Intelligence was normal. The 5-prime deletion, which accounts for about 30% of the alleles causing Sandhoff disease, results in the infantile form of the disorder when present in homozygous state. The pro405-to-leu mutation was observed in homozygous state in a juvenile onset form of Sandhoff disease in a Japanese patient by <a href="#50" class="mim-tip-reference" title="Wakamatsu, N., Kobayashi, H., Miyatake, T., Tsuji, S. <strong>A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3-prime splice site selection.</strong> J. Biol. Chem. 267: 2406-2413, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1531140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1531140</a>]" pmid="1531140">Wakamatsu et al. (1992)</a>. The same mutation in compound heterozygosity with the 5-prime deletion was observed in an adult French Canadian patient by <a href="#33" class="mim-tip-reference" title="McInnes, B., Potier, M., Wakamatsu, N., Melancon, S. B., Klavins, M. H., Tsuji, S., Mahuran, D. J. <strong>An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds.</strong> J. Clin. Invest. 90: 306-314, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1386607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1386607</a>] [<a href="https://doi.org/10.1172/JCI115863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1386607">McInnes et al. (1992)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1386607+7557963+1531140" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>.0011 HEXOSAMINIDASE B, HEAT-LABILE POLYMORPHISM</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121907984 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907984;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/rs121907984?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=rs121907984" 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=rs121907984" 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=RCV000004085 OR RCV000079061 OR RCV000987527" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004085, RCV000079061, RCV000987527" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004085...</a>
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<p>Genotyping individuals for Tay-Sachs disease (TSD) (<a href="/entry/272800">272800</a>) is based mainly on the heat lability of beta-hexosaminidase (Hex) A (<a href="/entry/606869">606869</a>) and the heat stability of Hex B. Mutations in the HEXB gene encoding the beta subunits of Hex that result in heat-labile hexosaminidase B thus may lead to erroneous enzymatic genotyping regarding TSD. Using single strand conformation polymorphism (SSCP) analysis for all 14 exons of HEXB followed by direct sequencing of aberrant fragments, <a href="#35" class="mim-tip-reference" title="Narkis, G., Adam, A., Jaber, L., Pennybacker, M., Proia, R. L., Navon, R. <strong>Molecular basis of heat labile hexosaminidase B among Jews and Arabs.</strong> Hum. Mutat. 10: 424-429, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9401004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9401004</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:6<424::AID-HUMU2>3.0.CO;2-D" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9401004">Narkis et al. (1997)</a> screened individuals whose Hex B was heat labile. These were Jewish and Arab individuals that had been identified by <a href="#36" class="mim-tip-reference" title="Navon, R., Adam, A. <strong>Thermolabile hexosaminidase (Hex) B: diverse frequencies among Jewish communities and implication for screening of sera for Hex A deficiencies.</strong> Hum. Hered. 40: 99-104, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2139865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2139865</a>] [<a href="https://doi.org/10.1159/000153913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2139865">Navon and Adam (1990)</a> and by <a href="#37" class="mim-tip-reference" title="Navon, R., Kopel, R., Nutman, J., Frisch, A., Conzelmann, E., Sandhoff, K., Adam, A. <strong>Hereditary heat-labile hexosaminidase B: a variant whose homozygotes synthesize a functional HEX A.</strong> Am. J. Hum. Genet. 37: 138-146, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3156493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3156493</a>]" pmid="3156493">Navon et al. (1985)</a>. The heat-labile mutation in these instances was identified as 1627 G-A. This caused an ala543-to-thr substitution in the beta-subunit protein. One individual with heat-labile Hex B was negative for the 1627 G-A mutation, as well as for the heat-labile mutation 1514 G-A (<a href="#0009">606873.0009</a>), proving that there exists at least one other heat-labile Hex B mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2139865+9401004+3156493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0012 SANDHOFF DISEASE, INFANTILE TYPE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs820878 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs820878;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/rs820878?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=rs820878" 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=rs820878" 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=RCV000004086 OR RCV000869482" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004086, RCV000869482" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004086...</a>
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<p><a href="#53" class="mim-tip-reference" title="Zhang, Z.-X., Wakamatsu, N., Akerman, B. R., Mules, E. H., Thomas, G. H., Gravel, R. A. <strong>A second, large deletion in the HEXB gene in a patient with infantile Sandhoff disease.</strong> Hum. Molec. Genet. 4: 777-780, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7633435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7633435</a>] [<a href="https://doi.org/10.1093/hmg/4.4.777" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7633435">Zhang et al. (1995)</a> found homozygosity for the ile207-to-val variant (<a href="#0005">606873.0005</a>) in the unaffected mother of a child with the infantile form of Sandhoff disease (<a href="/entry/268800">268800</a>). The child was compound heterozygous for a large, partial deletion of the HEXB gene and for an allele with a C-to-T substitution at nucleotide 185, which replaced ser62 with leu. The deletion originated in intron 6, approximately 2.5 kb from the beginning of exon 7, and appeared to extend approximately 25 kb beyond the 5-prime end of the gene. <a href="#53" class="mim-tip-reference" title="Zhang, Z.-X., Wakamatsu, N., Akerman, B. R., Mules, E. H., Thomas, G. H., Gravel, R. A. <strong>A second, large deletion in the HEXB gene in a patient with infantile Sandhoff disease.</strong> Hum. Molec. Genet. 4: 777-780, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7633435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7633435</a>] [<a href="https://doi.org/10.1093/hmg/4.4.777" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7633435">Zhang et al. (1995)</a> stated that this was the second largest deletion, after the very common 16-kb deletion (<a href="#0001">606873.0001</a>), to be reported. The 16-kb deletion, spanning the promoter, exons 1-5, and part of intron 5 of the HEXB gene, is the most common defect, accounting for 27% of Sandhoff alleles examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7633435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0013 SANDHOFF DISEASE, INFANTILE TYPE</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004087" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004087" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004087</a>
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<p>See <a href="#0012">606873.0012</a> and <a href="#53" class="mim-tip-reference" title="Zhang, Z.-X., Wakamatsu, N., Akerman, B. R., Mules, E. H., Thomas, G. H., Gravel, R. A. <strong>A second, large deletion in the HEXB gene in a patient with infantile Sandhoff disease.</strong> Hum. Molec. Genet. 4: 777-780, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7633435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7633435</a>] [<a href="https://doi.org/10.1093/hmg/4.4.777" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7633435">Zhang et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7633435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0014 SANDHOFF DISEASE, CHRONIC</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121907985 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907985;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/rs121907985?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=rs121907985" 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=rs121907985" 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=RCV000004088 OR RCV001238377" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004088, RCV001238377" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004088...</a>
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<p><a href="#47" class="mim-tip-reference" title="Rubin, M., Karpati, G., Wolfe, L. S., Carpenter, S., Klavins, M. H., Mahuran, D. J. <strong>Adult onset motor neuronopathy in the juvenile type of hexosaminidase A and B deficiency.</strong> J. Neurol. Sci. 87: 103-119, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2973515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2973515</a>] [<a href="https://doi.org/10.1016/0022-510x(88)90058-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2973515">Rubin et al. (1988)</a> described 2 sisters of French Canadian ancestry with a chronic Sandhoff phenotype (<a href="/entry/268800">268800</a>). <a href="#39" class="mim-tip-reference" title="Neote, K., McInnes, B., Mahuran, D. J., Gravel, R. A. <strong>Structure and distribution of an Alu-type deletion mutation in Sandhoff disease.</strong> J. Clin. Invest. 86: 1524-1531, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2147027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2147027</a>] [<a href="https://doi.org/10.1172/JCI114871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2147027">Neote et al. (1990)</a> demonstrated that these patients were heterozygous for the common 16-kb deletion of the 5-prime portion of the HEXB gene, (<a href="#0001">606873.0001</a>). Such alleles do not transcribe HEXB mRNA. <a href="#25" class="mim-tip-reference" title="Hou, Y., McInnes, B., Hinek, A., Karpati, G., Mahuran, D. <strong>A pro504-ser substitution in the beta-subunit of beta-hexosaminidase A inhibits alpha-subunit hydrolysis of G(M2) ganglioside, resulting in chronic Sandhoff disease.</strong> J. Biol. Chem. 273: 21386-21392, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9694901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9694901</a>] [<a href="https://doi.org/10.1074/jbc.273.33.21386" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9694901">Hou et al. (1998)</a> characterized the second mutant allele in these patients, a missense mutation in exon 13 of the HEXB gene that resulted in a pro504-to-ser amino acid substitution. This mutation produced a novel biochemical phenotype that impacted directly on the ability of HEXA to hydrolyze GM2. This was the first report of a mutation in the beta-subunit that affected the ability of HEXA to hydrolyze its natural, but not its artificial, substrates and that localized essential elements of the beta-chain from natural substrate hydrolysis to its C terminus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9694901+2973515+2147027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs5030731 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs5030731;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/rs5030731?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=rs5030731" 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=rs5030731" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#17" class="mim-tip-reference" title="Furihata, K., Drousiotou, A., Hara, Y., Christopoulos, G., Stylianidou, G., Anastasiadou, V., Ueno, I., Ioannou, P. <strong>Novel splice site mutation at IVS8 nt 5 of HEXB responsible for a Greek-Cypriot case of Sandhoff disease.</strong> Hum. Mutat. 13: 38-43, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9888387/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9888387</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)13:1<38::AID-HUMU4>3.0.CO;2-S" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9888387">Furihata et al. (1999)</a> determined the molecular basis of infantile Sandhoff disease (<a href="/entry/268800">268800</a>) in a Greek Cypriot patient. The proband had died at the age of 3 years and his parents were not available for study; the molecular analysis was performed on the mother's first cousin who was a carrier. A G-to-C transversion was identified in 1 allele of her HEXB gene at position 5 of the 5-prime splice site of intron 8. A cDNA clone derived from lymphocyte HEXB mRNA lacked the last 4 nucleotides, GTTG, of exon 8, which created a premature termination 11 codons downstream. In vivo transcription of the mutant HEXB gene in CHO cells showed deletion of the GTTG. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9888387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs1580377105 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1580377105;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=rs1580377105" 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=rs1580377105" 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=RCV000004090 OR RCV002512733" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004090, RCV002512733" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004090...</a>
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<p><a href="#23" class="mim-tip-reference" title="Hara, Y., Ioannou, P., Drousiotou, A., Stylianidou, G., Anastasiadou, V., Suzuki, K. <strong>Mutation analysis of a Sandhoff disease patient in the Maronite community in Cyprus.</strong> Hum. Genet. 94: 136-140, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8045559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8045559</a>] [<a href="https://doi.org/10.1007/BF00202858" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8045559">Hara et al. (1994)</a> found a 1-bp deletion, 76delA, in the HEXB gene in a patient from the Maronite community in Cyprus. <a href="#15" class="mim-tip-reference" title="Drousiotou, A., Stylianidou, G., Anastasiadou, V., Christopoulos, G., Mavrikiou, E., Georgiou, T., Kalakoutis, G., Oladimeja, A., Hara, Y., Suzuki, K., Furihata, K., Ueno, I., Ioannou, P. A., Fensom, A. H. <strong>Sandhoff disease in Cyprus: population screening by biochemical and DNA analysis indicates a high frequency of carriers in the Maronite community.</strong> Hum. Genet. 107: 12-17, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982028</a>] [<a href="https://doi.org/10.1007/s004390000324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982028">Drousiotou et al. (2000)</a> measured beta-hexosaminidases A and B in both leukocytes and serum in individuals from Cyprus and identified 35 carriers of Sandhoff disease (<a href="/entry/268800">268800</a>) among 244 random Maronite samples and 15 among 28 Maronites with a family history of Sandhoff disease, but only 1 carrier out of 115 random samples from the Greek community. Of the 50 Maronite carriers examined, 42 were found to have deletion of 76A. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10982028+8045559" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs121907986 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907986;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/rs121907986?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=rs121907986" 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=rs121907986" 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=RCV000004091 OR RCV000184012 OR RCV000579011" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004091, RCV000184012, RCV000579011" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004091...</a>
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<p>In 2 unrelated Italian patients with infantile Sandhoff disease (<a href="/entry/268800">268800</a>), <a href="#52" class="mim-tip-reference" title="Zampieri, S., Filocamo, M., Buratti, E., Stroppiano, M., Vlahovicek, K., Rosso, N., Bignulin, E., Regis, S., Carnevale, F., Bembi, B., Dardis, A. <strong>Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles.</strong> Neurogenetics 10: 49-58, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18758829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18758829</a>] [<a href="https://doi.org/10.1007/s10048-008-0145-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18758829">Zampieri et al. (2009)</a> identified a homozygous 850C-T transition in the HEXB gene, resulting in an arg284-to-ter (R284X) substitution. Although the mutation was present in 29% of the alleles from 12 unrelated Italian patients with infantile Sandhoff disease, haplotype analysis did not indicate a founder effect. The mutation occurred in a CpG dinucleotide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18758829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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> rs768438206 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs768438206;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/rs768438206?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=rs768438206" 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=rs768438206" 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=RCV000004092 OR RCV000673580" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004092, RCV000673580" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004092...</a>
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<p>In 2 Italian sibs with infantile Sandhoff disease (<a href="/entry/268800">268800</a>), <a href="#52" class="mim-tip-reference" title="Zampieri, S., Filocamo, M., Buratti, E., Stroppiano, M., Vlahovicek, K., Rosso, N., Bignulin, E., Regis, S., Carnevale, F., Bembi, B., Dardis, A. <strong>Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles.</strong> Neurogenetics 10: 49-58, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18758829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18758829</a>] [<a href="https://doi.org/10.1007/s10048-008-0145-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18758829">Zampieri et al. (2009)</a> identified a homozygous 1-bp deletion (965delT) in the HEXB gene, predicted to result in a frameshift and premature termination. In vitro functional expression studies showed that the deletion resulted in nonsense-mediated mRNA decay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18758829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">rs1554037088 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554037088;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=rs1554037088" 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=rs1554037088" 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=RCV001804177" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001804177" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001804177</a>
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<p>In 2 sibs with adult-onset Sandhoff disease (<a href="/entry/268800">268800</a>), <a href="#48" class="mim-tip-reference" title="Santoro, M., Modoni, A., Sabatelli, M., Madia, F., Piemonte, F., Tozzi, G., Ricci, E., Tonali, P. A., Silvestri, G. <strong>Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect.</strong> Molec. Genet. Metab. 91: 111-114, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17251047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17251047</a>] [<a href="https://doi.org/10.1016/j.ymgme.2006.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17251047">Santoro et al. (2007)</a> identified a homozygous c.1556A-G transition (c.1556A-G, NM_00521) in the HEXB gene, resulting in an asp494-to-gly (D494G) substitution at a conserved residue. The substitution led to reduced Hex and absent Hex-B enzymatic activity, possibly via disruption of beta-beta homodimer assembly. The c.1556A-G transition also disrupted an exon splicing enhancer motif in exon 12; RT-PCR studies revealed partial aberrant splicing of exon 12, resulting in a frameshift and premature termination downstream of exon 11 and leading to partial haploinsufficiency in addition to the homodimer assembly defect. The mutation segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17251047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#Chern1976" class="mim-tip-reference" title="Chern, C. J., Beutler, E., Kuhl, W., Gilbert, F., Mellman, W. J., Croce, C. M. <strong>Characterization of heteropolymeric hexosaminidase A in human X mouse hybrid cells.</strong> Proc. Nat. Acad. Sci. 73: 3637-3640, 1976.">Chern et al. (1976)</a>; <a href="#Fox1984" class="mim-tip-reference" title="Fox, M. F., DuToit, D. L., Warnich, L., Retief, A. E. <strong>Regional localization of alpha-galactosidase (GLA) to Xpter-q22, hexosaminidase B (HEXB) to 5q13-qter, and arylsulfatase B (ARSB) to 5pter-q13.</strong> Cytogenet. Cell Genet. 38: 45-49, 1984.">Fox et al. (1984)</a>; <a href="#George1977" class="mim-tip-reference" title="George, D. L., Francke, U. <strong>Regional mapping of human genes for hexosaminidase B and diphtheria toxin sensitivity on chromosome 5 using mouse X human hybrid cells.</strong> Somat. Cell Genet. 3: 629-638, 1977.">George and Francke (1977)</a>; <a href="#George1978" class="mim-tip-reference" title="George, D. L., Francke, U. <strong>Evidence for localization of the gene for hexosaminidase B to the cen-q13 region of human chromosome 5 using mouse-human hybrid cells.</strong> Cytogenet. Cell Genet. 22: 408-411, 1978.">George and Francke (1978)</a>; <a href="#Kleiman1994" class="mim-tip-reference" title="Kleiman, F. E., Dodelson de Kremer, R., Oller de Ramirez, A., Gravel, R. A., Argarana, C. E. <strong>Sandhoff disease in Argentina: high frequency of a splice site mutation in the HEXB gene and correlation between enzyme and DNA-based tests for heterozygote detection.</strong> Hum. Genet. 94: 279-282, 1994.">Kleiman et al. (1994)</a>; <a href="#Swallow1974" class="mim-tip-reference" title="Swallow, D. M., Stokes, D. C., Corney, G., Harris, H. <strong>Differences between the N-acetyl hexosaminidase isozymes in serum and tissues.</strong> Ann. Hum. Genet. 37: 287-302, 1974.">Swallow et al.
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(1974)</a>
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<a id="Banerjee1994" class="mim-anchor"></a>
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Banerjee, P., Boyers, M. J., Berry-Kravis, E., Dawson, G.
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<strong>Preferential beta-hexosaminidase (Hex) A (alpha-beta) formation in the absence of beta-Hex B (beta-beta) due to heterozygous point mutations present in beta-Hex beta-chain alleles of a motor neuron disease patient.</strong>
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J. Biol. Chem. 269: 4819-4826, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8106452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8106452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8106452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Banerjee, P., Siciliano, L., Oliveri, D., McCabe, N. R., Boyers, M. J., Horwitz, A. L., Li, S.-C., Dawson, G.
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<strong>Molecular basis of an adult form of beta-hexosaminidase B deficiency with motor neuron disease.</strong>
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Biochem. Biophys. Res. Commun. 181: 108-115, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1720305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1720305</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1720305" 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/s0006-291x(05)81388-9" target="_blank">Full Text</a>]
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Bapat, B., Ethier, M., Neote, K., Mahuran D., Gravel, R. A.
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<strong>Cloning and sequence analysis of a cDNA encoding the beta-subunit of mouse beta-hexosaminidase.</strong>
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FEBS Lett. 237: 191-195, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2971567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2971567</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2971567" 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/10.1016/0014-5793(88)80199-6" target="_blank">Full Text</a>]
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Beutler, E., Kuhl, W., Comings, D.
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<strong>Hexosaminidase isozyme in type O Gm2 gangliosidosis (Sandhoff-Jatzkewitz disease).</strong>
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Am. J. Hum. Genet. 27: 628-638, 1975.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/808963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">808963</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=808963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Bikker, H., van den Berg, F. M., Wolterman, R. A., de Vijlder, J. J. M., Bolhuis, P. A.
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<strong>Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis.</strong>
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Hum. Genet. 81: 287-288, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2921040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2921040</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2921040" 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/BF00279006" target="_blank">Full Text</a>]
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Bikker, H., van den Berg, F. M., Wolterman, R. A., Kleijer, W. J., de Vijlder, J. J. M., Bolhuis, P. A.
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<strong>Distribution and characterization of a Sandhoff disease-associated 50-kb deletion in the gene encoding the human beta-hexosaminidase beta-chain.</strong>
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Hum. Genet. 85: 327-329, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1975561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1975561</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1975561" 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/BF00206756" target="_blank">Full Text</a>]
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Bolhuis, P. A., Bikker, H.
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<strong>Deletion of the 5-prime-region in one or two alleles of HEXB in 15 out of 30 patients with Sandhoff disease (Letter)</strong>
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Hum. Genet. 90: 328-329, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1487253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1487253</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1487253" 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/BF00220096" target="_blank">Full Text</a>]
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Bolhuis, P. A., Oonk, J. G. W., Kamp, P. E., Ris, A. J., Michalski, J. C., Overdijk, B., Reuser, A. J. J.
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<strong>Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease.</strong>
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Neurology 37: 75-81, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2948136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2948136</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2948136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.37.1.75" target="_blank">Full Text</a>]
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Bolhuis, P. A., Ponne, N. J., Bikker, H., Baas, F., de Jong, J. M. B. V.
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<strong>Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.</strong>
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Biochim. Biophys. Acta 1182: 142-146, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8357844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8357844</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8357844" 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/10.1016/0925-4439(93)90134-m" target="_blank">Full Text</a>]
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Cashman, N. R., Antel, J. P., Hancock, L. W., Dawson, G., Horwitz, A. L., Johnson, W. G., Huttenlocher, P. R., Wollmann, R. L.
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<strong>N-acetyl-beta-hexosaminidase beta locus defect and juvenile motor neuron disease: a case study.</strong>
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Ann. Neurol. 19: 568-572, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3014997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3014997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3014997" 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/ana.410190608" target="_blank">Full Text</a>]
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Chern, C. J., Beutler, E., Kuhl, W., Gilbert, F., Mellman, W. J., Croce, C. M.
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<strong>Characterization of heteropolymeric hexosaminidase A in human X mouse hybrid cells.</strong>
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Proc. Nat. Acad. Sci. 73: 3637-3640, 1976.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/62363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">62363</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=62363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.73.10.3637" target="_blank">Full Text</a>]
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Dana, S., Wasmuth, J. J.
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<strong>Selective linkage disruption in human-Chinese hamster cell hybrids: deletion mapping of the leuS, hexB, emtB, and chr genes on human chromosome 5.</strong>
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Molec. Cell. Biol. 2: 1220-1228, 1982.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7177110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7177110</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7177110" 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/10.1128/mcb.2.10.1220-1228.1982" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s004390000324" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000132028" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)13:1<38::AID-HUMU4>3.0.CO;2-S" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF01539070" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000130984" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.72.1.263" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4812950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4812950</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4812950" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1469-1809.1974.tb01836.x" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="50" class="mim-anchor"></a>
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<a id="Wakamatsu1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wakamatsu, N., Kobayashi, H., Miyatake, T., Tsuji, S.
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<strong>A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3-prime splice site selection.</strong>
|
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J. Biol. Chem. 267: 2406-2413, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1531140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1531140</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1531140" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</li>
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<li>
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<a id="51" class="mim-anchor"></a>
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<a id="Wood1976" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wood, S., MacDougall, B. G.
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<strong>Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts.</strong>
|
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Am. J. Hum. Genet. 28: 489-495, 1976.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</li>
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<li>
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<a id="52" class="mim-anchor"></a>
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<a id="Zampieri2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zampieri, S., Filocamo, M., Buratti, E., Stroppiano, M., Vlahovicek, K., Rosso, N., Bignulin, E., Regis, S., Carnevale, F., Bembi, B., Dardis, A.
|
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<strong>Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles.</strong>
|
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Neurogenetics 10: 49-58, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18758829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18758829</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18758829" 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/s10048-008-0145-1" target="_blank">Full Text</a>]
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</p>
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</li>
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<li>
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<a id="53" class="mim-anchor"></a>
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<a id="Zhang1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, Z.-X., Wakamatsu, N., Akerman, B. R., Mules, E. H., Thomas, G. H., Gravel, R. A.
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<strong>A second, large deletion in the HEXB gene in a patient with infantile Sandhoff disease.</strong>
|
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Hum. Molec. Genet. 4: 777-780, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7633435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7633435</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7633435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/4.4.777" target="_blank">Full Text</a>]
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</ol>
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<div>
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<br />
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 04/20/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 3/25/2009<br>Paul J. Converse - updated : 3/3/2008<br>George E. Tiller - updated : 5/31/2007
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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="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin : 4/24/2002
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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="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/21/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/20/2020<br>carol : 07/14/2016<br>carol : 12/30/2014<br>alopez : 12/10/2014<br>carol : 9/19/2013<br>carol : 11/4/2009<br>wwang : 4/15/2009<br>wwang : 4/10/2009<br>ckniffin : 3/25/2009<br>ckniffin : 3/25/2009<br>mgross : 3/3/2008<br>wwang : 5/31/2007<br>alopez : 11/14/2003<br>carol : 5/7/2002<br>ckniffin : 5/6/2002
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</span>
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</div>
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</div>
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<div class="container visible-print-block">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606873
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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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HEXOSAMINIDASE B; HEXB
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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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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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ENC1, ANTISENSE, INCLUDED; ENC1AS, INCLUDED
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</span>
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</div>
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</div>
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<div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: HEXB</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> 23849003;
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<strong>ICD10CM:</strong> E75.01;
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</span>
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</p>
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<div>
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<br />
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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: 5q13.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 5:74,640,023-74,721,288 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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5q13.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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Sandhoff disease, infantile, juvenile, and adult forms
|
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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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268800
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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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<br />
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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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<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>The HEXB gene encodes the beta subunit of the enzyme hexosaminidase (EC 3.2.1.52), which is involved in the breakdown of gangliosides. There are 2 isoenzymes of hexosaminidase: Hex-A, which is encoded by the HEXA gene (606869), and Hex-B. Beutler et al. (1975) concluded that Hex-A has the structure alpha-beta, whereas Hex-B has the structure beta-beta. </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>O'Dowd et al. (1985) cloned a human HEXB cDNA from an SV40-transformed fibroblast cDNA library. The cDNA encodes a deduced 556-amino acid protein. </p><p>Bapat et al. (1988) cloned the murine beta subunit of hexosaminidase. The cDNA corresponded to a polypeptide of 536 amino acids, which shows 75% homology with the human peptide. </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>Proia (1988) showed that the beta-chain coding region is divided into 14 exons distributed over about 40 kb of DNA. Comparison with the alpha-chain gene showed that 12 of the 13 introns interrupt the coding regions at homologous positions. This extensive sharing of intron placement demonstrates that the alpha and beta chains evolved by way of duplication of a common ancestor. </p><p>Neote et al. (1988) determined that the promoter region of the HEXB gene is GC-rich, with several GC boxes and a CAAT box. </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>Hechtman and Rowlands (1979) studied a temperature-sensitive mutant of hexosaminidase B. Mahuran et al. (1982) provided biochemical evidence that the beta(2) subunit may consist of 2 dissimilar polypeptide chains: beta(a)beta(b). Genetic data suggest that these are the product of a single locus. </p><p>Pennybacker et al. (1996) identified domains in human hexosaminidase that confer distinctive substrate specificity to Hex-A (composed of alpha-beta chains), Hex-B (beta-beta), and Hex-S (alpha-alpha) isozymes. The active site on the beta subunit primarily degrades neutral substrates while the alpha-subunit site is active against sulfated substrates. Only Hex-A, together with the GM2 activator protein, can degrade GM2 ganglioside. Pennybacker et al. (1996) generated chimeric hexosaminidase subunits by interchanging analogous regions of the alpha and beta subunits. Chimeric constructs were expressed in HeLa cells and selected constructs were produced in the baculovirus expression system to determine their ability to degrade GM2 ganglioside in the presence of GM2 activator protein. Their results allowed them to define 2 noncontiguous sequences in the alpha subunit (amino acids 1-191 and 403-529) which, when substituted into analogous positions in the beta subunit, conferred activity against the sulfated substrate. Pennybacker et al. (1996) also found that amino acids 225-556 in the beta subunit are required for activator-dependent GM2 ganglioside degradation by HEXA. </p><p>Alterations in chromosome 5q13 are a frequent finding in hairy cell leukemia (HCL). Hammarsund et al. (2004) reported that a 5q13.3 breakpoint discovered in an HCL patient disrupted a conserved alternative isoform of HEXB. This isoform directly overlapped, in a cis-antisense fashion, exon 1 of ENC1 (605173), and was thus named ENC1AS. Purified HCL tumor cells from 26 HCL patients showed striking upregulation of ENC1 in all 26 samples analyzed. Hammarsund et al. (2004) identified a complex 5-prime regulatory mechanism involving an inverse expression of the ENC1 and the ENC1AS transcripts in several tissues, suggesting that expression of ENC1AS may regulate ENC1 levels. </p><p>Using RNA interference to deplete host genes in Mycobacterium marinum (Mm)-infected Drosophila S2 cells, which share properties with mammalian macrophages, Koo et al. (2008) identified a mycobactericidal role for Hexb. They confirmed the importance of mammalian Hexb in controlling Mm growth using macrophages from Hexb -/- mice. Treatment of Hexb -/- mouse cells with Ifng (147570) abolished their susceptibility to Mm. Exposure of mouse macrophages to Mm, with or without phagocytosis, induced Hexb secretion, suggesting that Mm comes into contact with Hexb at the plasma membrane. Incubation of Mm with Hexb, at neutral or acidic pH, killed Mm. Koo et al. (2008) concluded that HEXB is a peptidoglycan hydrolase and proposed that it is involved in restricting mycobacteria growth even before the onset of adaptive immunity. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>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>The HEXB locus has been assigned to chromosome 5 (Gilbert et al., 1975). </p><p>Various Sandhoff strains, even cells from the infantile and the rare juvenile forms, fail to complement in heterokaryons, suggesting that these are the result of allelic mutations in the beta subunit of HEXB. Dana and Wasmuth (1982) did cytogenetic and biochemical analyses of spontaneous segregants from Chinese hamster-human interspecific hybrid cells (which contained human chromosome 5 and expressed the 4 syntenic genes LEUS, HEXB, EMTB, and CHR), the hybrid cell being subjected to selective conditions requiring them to retain the LEUS gene. From these analyses, Dana and Wasmuth (1982) concluded that the order is as listed above and that the specific locations are: LEUS, 5pter-q1; HEXB, 5q13; EMTB, 5q23-q35; CHR, 5q35. In a child with a de novo balanced translocation t(5;13)(q11;p11), Mattei et al. (1984) found decreased levels of Hex-B, suggesting to these workers that the HEXB gene assignment can be narrowed to 5q11. </p><p>Killary et al. (1986) assigned the HEXB locus to mouse chromosome 13 by study of mouse-hamster hybrids.</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>O'Brien (1978) made suggestions for the nomenclature of alleles at the HEX alpha and beta loci. The alleles at the beta locus in his system are numbered as follows: 1--wildtype; 2--Sandhoff; 3--normal with deficient Hex-A and Hex-B. </p><p>Bikker et al. (1989) demonstrated a 16-kb deletion in 1 allele of the HEXB gene (606873.0001) in 2 apparently unrelated patients with Sandhoff disease (268800) </p><p>Oonk et al. (1979) reported the cases of 2 adult sisters with spinocerebellar degeneration and very low activities of both Hex-A and Hex-B. Bolhuis et al. (1987) concluded that the disorder was the result of a 'destabilizing mutation' in the HEXB locus. Bolhuis et al. (1993) demonstrated that these 2 sisters were compound heterozygotes for an mRNA-negative allele on 1 chromosome 5 and an R505Q mutation (606873.0009) on the homologous chromosome. Transfection of COS cells with a cDNA construct containing the R505Q mutation resulted in the expression of a labile form of beta-hexosaminidase, thus confirming their earlier conclusion. </p><p>Neufeld (1989) provided a review of the disorders related to mutations in the HEXA and HEXB genes. Mahuran (1998) stated that he maintains a database of published hexosaminidase and GM2A (613109) mutations and that the database contains 23 HEXB mutations, 86 HEXA (606869) mutations, and 4 GM2A mutations. </p><p>Among 12 unrelated Italian patients with Sandhoff disease, 11 of whom had the infantile type, Zampieri et al. (2009) identified 11 different mutations in the HEXB gene, including 6 novel mutations (see, e.g., 606873.0017 and 606873.0018). The common 16-kb deletion (606873.0001) was not identified in this patient cohort. </p><p>In 2 sibs with adult-type Sandhoff disease, Santoro et al. (2007) identified homozygosity for a missense mutation in the HEXB gene (D494G; 606873.0019). Leukocyte enzyme analysis showed reduced total Hex activity, absent Hex-B activity, and normal Hex-A activity. The mutation segregated with the disorder in the family. </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>19 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 SANDHOFF DISEASE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HEXB, 16-KB DEL
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<br />
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ClinVar: RCV000004077
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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>By field inversion gel electrophoresis (FIGE) of SfiI-digested chromosomal DNA, Bikker et al. (1989) demonstrated a 16-kb deletion in 1 allele of the HEXB gene in 2 apparently unrelated patients with Sandhoff disease (268800). Mahuran (1994) pointed out that the 50-kb deletion (50-KB DEL) originally reported by Bikker et al. (1989) is the same as the 16-kb deletion described by Neote et al. (1990). The size was incorrectly estimated by Bikker et al. (1989); see Bolhuis and Bikker (1992). In conventional Southern blot analysis, this deletion was masked by hybridization of bands from the other allele. Among 14 patients with Sandhoff disease from different parts of Europe, Bikker et al. (1990) found homozygosity for the deletion in 2 and heterozygosity in 7. It appeared that the deletion started in intron 5, extending in the 5-prime direction and causing the loss of exons 1 to 5 and the promoter area of the HEXB gene. </p><p>In DNA from fibroblasts of a patient with the infantile form of Sandhoff disease, Neote et al. (1990) identified a deletion of approximately 16 kb, including the HEXB promoter, exons 1 through 5, and part of intron 5. The deletion probably arose from recombination between 2 Alu sequences, with the breakpoints occurring at the midpoint between the left and right arms in each case and regenerating an intact Alu element in the deletion sequence. The deletion allele accounted for 8 of 30 Sandhoff mutant alleles analyzed. It was present in homozygous state in 2 cell lines from patients with the infantile form, in heterozygous form together with an intron 12 deletion in a juvenile case, and in heterozygous form in 2 adult Sandhoff cases. The last 3 cases plus 1 infantile case had the Alu-type deletion in compound heterozygous (i.e., heteroallelic) state (see 606873.0014). McInnes et al. (1992) reported that this 16-kb deletion accounted for 27% of the Sandhoff alleles they analyzed. This null allele was associated with the juvenile pro417-to-leu mutation (606873.0007) which interfered with the normal acceptor splice site. This combination in a French Canadian family was accompanied by a very mild phenotype which McInnes et al. (1992) attributed to differences in racial background. </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 SANDHOFF DISEASE, JUVENILE TYPE</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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HEXB, 24-BP INS
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<br />
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SNP: rs201580118,
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gnomAD: rs201580118,
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ClinVar: RCV000633008, RCV002286417, RCV002529814, RCV003153772
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a case of the juvenile form of Sandhoff disease (268800) reported by Wood and MacDougall (1976), Nakano and Suzuki (1989) showed that a cDNA clone isolated from fibroblasts contained an extra 24-base segment between exons 12 and 13. This segment was identified as the 3-prime terminus of intron 12. The remainder of the coding sequence was completely normal. The insertion was 'in frame' and added 8 amino acids between amino acids 491 and 492 of the enzyme protein. It was located only 5 amino acids away from a possible glycosylation site. Gene amplification by the PCR and subsequent sequencing of genomic DNA showed that the patient was a compound heterozygote. In 1 allele there was a single nucleotide transition from normal G to A at 26 bases from the 3-prime terminus of intron 12. This mutation generated a consensus sequence for the 3-prime splice site for an intron and thus explained the abnormal mRNAs that retain 24 bases of the 3-prime terminus of intron 12. The intron 12 and flanking exons 12 and 13 sequences were normal in the other allele. The other mutant allele was thought to be of an mRNA-negative type. The same mutation was found in a 35-year-old Japanese man with manifestations of juvenile Sandhoff disease: progressive neurogenic muscular atrophy, cerebellar ataxia, and mental deterioration beginning at age 10. Dlott et al. (1990) found the same mutation in cells from 2 juvenile Sandhoff disease patients and a third, asymptomatic individual. </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 HEXOSAMINIDASE B (PARIS)</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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HEXB, 18-BP INS
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<br />
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SNP: rs1554037309,
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ClinVar: RCV000596163, RCV000674261, RCV002286414
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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>Dreyfus et al. (1977) characterized a hexosaminidase variant that may represent unstable beta subunits. Dlott et al. (1990) demonstrated that this so-called 'hexosaminidase Paris' had an abnormally elongated beta subunit due to duplication of a region straddling the junction of intron 13 and exon 14, which generated an alternate splice site and caused an in-frame insertion of 18 nucleotides into the mRNA. The normal splice site seemed to be used to some extent, accounting for the residual Hex-A isoenzyme 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-text-font">
|
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<strong>.0004 MOVED TO 606873.0001</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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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0005 HEXB POLYMORPHISM</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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HEXB, ILE207VAL
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<br />
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SNP: rs10805890,
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gnomAD: rs10805890,
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ClinVar: RCV000079065, RCV000235014, RCV000403428, RCV000675619
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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>The ile207-to-val substitution was found to be a common polymorphism by Zhang et al. (1995) and Redonnet-Vernhet et al. (1996). </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>.0006 SANDHOFF DISEASE, JUVENILE TYPE</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
HEXB, TYR456SER
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<br />
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SNP: rs121907982,
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gnomAD: rs121907982,
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ClinVar: RCV000004081, RCV000675054, RCV001553740, RCV004719618
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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 female patient with juvenile onset of Sandhoff disease (268800) manifest as a motor neuron disease (Cashman et al., 1986), Banerjee et al. (1991) found a heterozygous 1367A-C transversion in the HEXB gene, resulting in a tyr456-to-ser (Y456S) substitution derived from the maternal allele. The patient was also heterozygous for 2 polymorphisms: a 619A-G transition resulting in an ile207-to-val (I207V) substitution from the paternal allele, and K121R (606873.0008). The patient had progressive motor neuron disease that began at age 7 and was characterized by dysarthria, muscle wasting, fasciculations, and pyramidal tract dysfunction. Rectal biopsy at age 24 showed membranous cytoplasmic bodies in submucosal ganglion cells. Biochemical studies showed partial HexA (30-50% of controls) with absence of HexB. The unaffected mother also had partial HexA and partial HexB deficiency. In vitro functional expression studies by Banerjee et al. (1994) showed that the Y456S variant was completely nonfunctional and was predicted to interfere with formation of a functional dimer. Banerjee et al. (1994) proposed that the variant I207V beta-chain inherited from the father must undergo preferential association with the normal alpha-chains in the patient, thus producing only HexA. Further studies indicated that the I207V beta-chain does not self-associate at low concentrations. Thus, in a patient with a nonfunctional HEXB allele, the effective concentration of beta-chains is reduced to 50% of normal, and the remaining I207V chains fail to self-associate to form HexB, but can still dimerize with the abundant normal alpha-chains, thus producing partial beta-Hex A and no beta-Hex B. </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>.0007 SANDHOFF DISEASE, JUVENILE TYPE</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
HEXB, PRO417LEU
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<br />
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|
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SNP: rs28942073,
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gnomAD: rs28942073,
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ClinVar: RCV000004082, RCV000004084, RCV000079058, RCV000174009, RCV002251870, RCV003407272, RCV004018549
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|
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|
|
</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Wakamatsu et al. (1992) studied a 39-year-old Japanese male with a mild clinical presentation of mental retardation and 'local panatrophy.' The parents were first cousins. HEXB activity was undetectable in the patient's leukocytes and fibroblasts and HEXA activity was decreased to 6 and 8% of control values, respectively. Rectal biopsy demonstrated membranous cytoplasmic bodies in neurons of Meissner plexus. The urine contained large amounts of neutral oligosaccharides. Wakamatsu et al. (1992) discovered a novel exon mutation affecting 3-prime splice site selection. Nucleotide sequence analysis of the HEXB gene showed 2 single base substitutions, one in exon 2 (A to G, a known polymorphism) and the other in exon 11 (C to T). Analysis of the beta-subunit mRNA demonstrated activation of a cryptic splice site in exon 11 as well as skipping of the exon. A transfection assay using a chimeric gene containing intron 10 flanked by cDNA sequences carrying the mutation confirmed that the single base substitution located at position 8 of exon 11 inhibited the selection of the normal 3-prime splice site. The CCG-to-CTG mutation resulted in substitution of leucine for proline-417 in exon 11. The mutation was present in homozygous state in the patient and in heterozygous state in the parents and a sister. Its effect was to abolish an MspI site. </p><p>McInnes et al. (1992) described a 57-year-old man with very mild manifestations of Sandhoff disease (268800) although his genotype and low residual enzyme activity were considered predictive of the much more severe juvenile Sandhoff disease. They demonstrated that the patient was a genetic compound of the infantile 5-prime deletion mutation described by Neote et al. (1990), a null mutation (606873.0001), and the juvenile intron 10/exon 11 C-to-T mutation. Of his 6 clinically unaffected sibs, 4 of them, ranging in age from 51 to 62 years, were also genetic compounds for the same 2 Sandhoff alleles. The variable phenotype associated with the intron 10/exon 11 C-to-T transition indicates that other unidentified factors determine the pathologic outcome of the mutation. Genetic variations in the RNA splicing machinery may be the explanation. The patient, a French Canadian, had had severe watery diarrhea over a 9-year period with intermittent moderate and diffuse abdominal pain, a 17-kg weight loss over a 7-year period, and increasing weakness. Physical examination showed lower limb hyperreflexia and impaired thermal sensitivity of legs and arms. Intolerance to warm weather due to impaired sweating, impaired sexual function progressing to complete impotence, mild urinary incontinence, and orthostatic hypotension were noted. One of the sisters, aged 58, had complained of diarrhea for 10 years and postural dizziness for 5 years. </p>
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|
</span>
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</div>
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<div>
|
|
<br />
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|
</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 HEXB POLYMORPHISM</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
HEXB, LYS121ARG
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<br />
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SNP: rs11556045,
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gnomAD: rs11556045,
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|
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ClinVar: RCV000004078, RCV000079063, RCV000336190, RCV000675618
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|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In the course of studying a case of juvenile Sandhoff disease (268800), Wakamatsu et al. (1992) found the AAA-to-AGA polymorphism in exon 2, which results in alternative substitution of arginine for lysine-121. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0009 SANDHOFF DISEASE, ADULT TYPE</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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HEXB, ARG505GLN
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<br />
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SNP: rs121907983,
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gnomAD: rs121907983,
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ClinVar: RCV000004083, RCV000669552
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 2 sisters with adult Sandhoff disease (268800) presenting as spinocerebellar degeneration, reported by Oonk et al. (1979) and previously studied by Bolhuis et al. (1987), Bolhuis et al. (1993) found that the HEXB gene contained a G-to-A transition at nucleotide position 1514, resulting in a change in the electric charge at amino acid position 505 by substitution of glutamine for arginine in a highly conserved part of the beta chain. The nucleotide transition generated a new restriction site for DdeI, which was present in only 1 of the alleles. Bolhuis et al. (1993) demonstrated that the second allele was of mRNA-negative type. Thus, the patient was a genetic compound. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0010 SANDHOFF DISEASE, ADULT TYPE</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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HEXB, PRO405LEU
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<br />
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SNP: rs28942073,
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gnomAD: rs28942073,
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ClinVar: RCV000004082, RCV000004084, RCV000079058, RCV000174009, RCV002251870, RCV003407272, RCV004018549
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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 35-year-old man who was evaluated at age 30 years because of slowly progressive lower limb weakness and diffuse fasciculations, Gomez-Lira et al. (1995) found compound heterozygosity with a common deletion at the 5-prime end of the HEXB gene and a C-to-T transition at nucleotide 1214, resulting in a pro405-to-leu amino acid substitution in the gene product. The patient was an executive secretary and had been a rock climber until age 29 years, when lower limb weakness began. On neurologic examination, moderate reduction in strength, widespread spontaneous fasciculations, and hyperactive deep tendon reflexes were observed. Intelligence was normal. The 5-prime deletion, which accounts for about 30% of the alleles causing Sandhoff disease, results in the infantile form of the disorder when present in homozygous state. The pro405-to-leu mutation was observed in homozygous state in a juvenile onset form of Sandhoff disease in a Japanese patient by Wakamatsu et al. (1992). The same mutation in compound heterozygosity with the 5-prime deletion was observed in an adult French Canadian patient by McInnes et al. (1992). </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0011 HEXOSAMINIDASE B, HEAT-LABILE POLYMORPHISM</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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|
HEXB, ALA543THR
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<br />
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|
|
SNP: rs121907984,
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|
|
gnomAD: rs121907984,
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|
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|
|
ClinVar: RCV000004085, RCV000079061, RCV000987527
|
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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>Genotyping individuals for Tay-Sachs disease (TSD) (272800) is based mainly on the heat lability of beta-hexosaminidase (Hex) A (606869) and the heat stability of Hex B. Mutations in the HEXB gene encoding the beta subunits of Hex that result in heat-labile hexosaminidase B thus may lead to erroneous enzymatic genotyping regarding TSD. Using single strand conformation polymorphism (SSCP) analysis for all 14 exons of HEXB followed by direct sequencing of aberrant fragments, Narkis et al. (1997) screened individuals whose Hex B was heat labile. These were Jewish and Arab individuals that had been identified by Navon and Adam (1990) and by Navon et al. (1985). The heat-labile mutation in these instances was identified as 1627 G-A. This caused an ala543-to-thr substitution in the beta-subunit protein. One individual with heat-labile Hex B was negative for the 1627 G-A mutation, as well as for the heat-labile mutation 1514 G-A (606873.0009), proving that there exists at least one other heat-labile Hex B 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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 SANDHOFF DISEASE, INFANTILE TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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|
HEXB, SER62LEU
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<br />
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SNP: rs820878,
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gnomAD: rs820878,
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|
|
ClinVar: RCV000004086, RCV000869482
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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>Zhang et al. (1995) found homozygosity for the ile207-to-val variant (606873.0005) in the unaffected mother of a child with the infantile form of Sandhoff disease (268800). The child was compound heterozygous for a large, partial deletion of the HEXB gene and for an allele with a C-to-T substitution at nucleotide 185, which replaced ser62 with leu. The deletion originated in intron 6, approximately 2.5 kb from the beginning of exon 7, and appeared to extend approximately 25 kb beyond the 5-prime end of the gene. Zhang et al. (1995) stated that this was the second largest deletion, after the very common 16-kb deletion (606873.0001), to be reported. The 16-kb deletion, spanning the promoter, exons 1-5, and part of intron 5 of the HEXB gene, is the most common defect, accounting for 27% of Sandhoff alleles examined. </p>
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|
</span>
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</div>
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<div>
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|
<br />
|
|
</div>
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</div>
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|
<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 SANDHOFF DISEASE, INFANTILE TYPE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
HEXB, PARTIAL DEL
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|
|
<br />
|
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|
|
ClinVar: RCV000004087
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|
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|
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</span>
|
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</div>
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 606873.0012 and Zhang et al. (1995). </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 SANDHOFF DISEASE, CHRONIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
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|
|
|
HEXB, PRO504SER
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<br />
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|
SNP: rs121907985,
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|
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|
|
gnomAD: rs121907985,
|
|
|
|
|
|
ClinVar: RCV000004088, RCV001238377
|
|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Rubin et al. (1988) described 2 sisters of French Canadian ancestry with a chronic Sandhoff phenotype (268800). Neote et al. (1990) demonstrated that these patients were heterozygous for the common 16-kb deletion of the 5-prime portion of the HEXB gene, (606873.0001). Such alleles do not transcribe HEXB mRNA. Hou et al. (1998) characterized the second mutant allele in these patients, a missense mutation in exon 13 of the HEXB gene that resulted in a pro504-to-ser amino acid substitution. This mutation produced a novel biochemical phenotype that impacted directly on the ability of HEXA to hydrolyze GM2. This was the first report of a mutation in the beta-subunit that affected the ability of HEXA to hydrolyze its natural, but not its artificial, substrates and that localized essential elements of the beta-chain from natural substrate hydrolysis to its C terminus. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 SANDHOFF DISEASE, INFANTILE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HEXB, IVS8, G-C, +5
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs5030731,
|
|
|
|
|
|
gnomAD: rs5030731,
|
|
|
|
|
|
ClinVar: RCV000004089
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Furihata et al. (1999) determined the molecular basis of infantile Sandhoff disease (268800) in a Greek Cypriot patient. The proband had died at the age of 3 years and his parents were not available for study; the molecular analysis was performed on the mother's first cousin who was a carrier. A G-to-C transversion was identified in 1 allele of her HEXB gene at position 5 of the 5-prime splice site of intron 8. A cDNA clone derived from lymphocyte HEXB mRNA lacked the last 4 nucleotides, GTTG, of exon 8, which created a premature termination 11 codons downstream. In vivo transcription of the mutant HEXB gene in CHO cells showed deletion of the GTTG. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 SANDHOFF DISEASE, INFANTILE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HEXB, 1-BP DEL, 76A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1580377105,
|
|
|
|
|
|
|
|
ClinVar: RCV000004090, RCV002512733
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Hara et al. (1994) found a 1-bp deletion, 76delA, in the HEXB gene in a patient from the Maronite community in Cyprus. Drousiotou et al. (2000) measured beta-hexosaminidases A and B in both leukocytes and serum in individuals from Cyprus and identified 35 carriers of Sandhoff disease (268800) among 244 random Maronite samples and 15 among 28 Maronites with a family history of Sandhoff disease, but only 1 carrier out of 115 random samples from the Greek community. Of the 50 Maronite carriers examined, 42 were found to have deletion of 76A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 SANDHOFF DISEASE, INFANTILE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HEXB, ARG284TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121907986,
|
|
|
|
|
|
gnomAD: rs121907986,
|
|
|
|
|
|
ClinVar: RCV000004091, RCV000184012, RCV000579011
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated Italian patients with infantile Sandhoff disease (268800), Zampieri et al. (2009) identified a homozygous 850C-T transition in the HEXB gene, resulting in an arg284-to-ter (R284X) substitution. Although the mutation was present in 29% of the alleles from 12 unrelated Italian patients with infantile Sandhoff disease, haplotype analysis did not indicate a founder effect. The mutation occurred in a CpG dinucleotide. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 SANDHOFF DISEASE, INFANTILE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HEXB, 1-BP DEL, 965T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs768438206,
|
|
|
|
|
|
gnomAD: rs768438206,
|
|
|
|
|
|
ClinVar: RCV000004092, RCV000673580
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Italian sibs with infantile Sandhoff disease (268800), Zampieri et al. (2009) identified a homozygous 1-bp deletion (965delT) in the HEXB gene, predicted to result in a frameshift and premature termination. In vitro functional expression studies showed that the deletion resulted in nonsense-mediated mRNA decay. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 SANDHOFF DISEASE, ADULT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HEXB, ASP494GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1554037088,
|
|
|
|
|
|
|
|
ClinVar: RCV001804177
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with adult-onset Sandhoff disease (268800), Santoro et al. (2007) identified a homozygous c.1556A-G transition (c.1556A-G, NM_00521) in the HEXB gene, resulting in an asp494-to-gly (D494G) substitution at a conserved residue. The substitution led to reduced Hex and absent Hex-B enzymatic activity, possibly via disruption of beta-beta homodimer assembly. The c.1556A-G transition also disrupted an exon splicing enhancer motif in exon 12; RT-PCR studies revealed partial aberrant splicing of exon 12, resulting in a frameshift and premature termination downstream of exon 11 and leading to partial haploinsufficiency in addition to the homodimer assembly defect. The mutation segregated with the disorder in the family. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Chern et al. (1976); Fox et al. (1984); George and Francke (1977);
|
|
George and Francke (1978); Kleiman et al. (1994); Swallow et al.
|
|
(1974)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Banerjee, P., Boyers, M. J., Berry-Kravis, E., Dawson, G.
|
|
<strong>Preferential beta-hexosaminidase (Hex) A (alpha-beta) formation in the absence of beta-Hex B (beta-beta) due to heterozygous point mutations present in beta-Hex beta-chain alleles of a motor neuron disease patient.</strong>
|
|
J. Biol. Chem. 269: 4819-4826, 1994.
|
|
|
|
|
|
[PubMed: 8106452]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Banerjee, P., Siciliano, L., Oliveri, D., McCabe, N. R., Boyers, M. J., Horwitz, A. L., Li, S.-C., Dawson, G.
|
|
<strong>Molecular basis of an adult form of beta-hexosaminidase B deficiency with motor neuron disease.</strong>
|
|
Biochem. Biophys. Res. Commun. 181: 108-115, 1991.
|
|
|
|
|
|
[PubMed: 1720305]
|
|
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|
|
[Full Text: https://doi.org/10.1016/s0006-291x(05)81388-9]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bapat, B., Ethier, M., Neote, K., Mahuran D., Gravel, R. A.
|
|
<strong>Cloning and sequence analysis of a cDNA encoding the beta-subunit of mouse beta-hexosaminidase.</strong>
|
|
FEBS Lett. 237: 191-195, 1988.
|
|
|
|
|
|
[PubMed: 2971567]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0014-5793(88)80199-6]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beutler, E., Kuhl, W., Comings, D.
|
|
<strong>Hexosaminidase isozyme in type O Gm2 gangliosidosis (Sandhoff-Jatzkewitz disease).</strong>
|
|
Am. J. Hum. Genet. 27: 628-638, 1975.
|
|
|
|
|
|
[PubMed: 808963]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bikker, H., van den Berg, F. M., Wolterman, R. A., de Vijlder, J. J. M., Bolhuis, P. A.
|
|
<strong>Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis.</strong>
|
|
Hum. Genet. 81: 287-288, 1989.
|
|
|
|
|
|
[PubMed: 2921040]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00279006]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bikker, H., van den Berg, F. M., Wolterman, R. A., Kleijer, W. J., de Vijlder, J. J. M., Bolhuis, P. A.
|
|
<strong>Distribution and characterization of a Sandhoff disease-associated 50-kb deletion in the gene encoding the human beta-hexosaminidase beta-chain.</strong>
|
|
Hum. Genet. 85: 327-329, 1990.
|
|
|
|
|
|
[PubMed: 1975561]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00206756]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bolhuis, P. A., Bikker, H.
|
|
<strong>Deletion of the 5-prime-region in one or two alleles of HEXB in 15 out of 30 patients with Sandhoff disease (Letter)</strong>
|
|
Hum. Genet. 90: 328-329, 1992.
|
|
|
|
|
|
[PubMed: 1487253]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00220096]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bolhuis, P. A., Oonk, J. G. W., Kamp, P. E., Ris, A. J., Michalski, J. C., Overdijk, B., Reuser, A. J. J.
|
|
<strong>Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease.</strong>
|
|
Neurology 37: 75-81, 1987.
|
|
|
|
|
|
[PubMed: 2948136]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.37.1.75]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bolhuis, P. A., Ponne, N. J., Bikker, H., Baas, F., de Jong, J. M. B. V.
|
|
<strong>Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.</strong>
|
|
Biochim. Biophys. Acta 1182: 142-146, 1993.
|
|
|
|
|
|
[PubMed: 8357844]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0925-4439(93)90134-m]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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<strong>Significance of two point mutations present in each HEXB allele of patients with adult G-M2 gangliosidosis (Sandhoff disease): homozygosity for the ile207-to-val substitution is not associated with a clinical or biochemical phenotype.</strong>
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<strong>Adult onset motor neuronopathy in the juvenile type of hexosaminidase A and B deficiency.</strong>
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<strong>Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect.</strong>
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<strong>Differences between the N-acetyl hexosaminidase isozymes in serum and tissues.</strong>
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Wakamatsu, N., Kobayashi, H., Miyatake, T., Tsuji, S.
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<strong>A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3-prime splice site selection.</strong>
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Wood, S., MacDougall, B. G.
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<strong>Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts.</strong>
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Am. J. Hum. Genet. 28: 489-495, 1976.
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[PubMed: 10724]
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Zampieri, S., Filocamo, M., Buratti, E., Stroppiano, M., Vlahovicek, K., Rosso, N., Bignulin, E., Regis, S., Carnevale, F., Bembi, B., Dardis, A.
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<strong>Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles.</strong>
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[PubMed: 18758829]
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Zhang, Z.-X., Wakamatsu, N., Akerman, B. R., Mules, E. H., Thomas, G. H., Gravel, R. A.
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<strong>A second, large deletion in the HEXB gene in a patient with infantile Sandhoff disease.</strong>
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[PubMed: 7633435]
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