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Entry
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- #272750 - GM2-GANGLIOSIDOSIS, AB VARIANT
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- OMIM
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<p>
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<span class="h4">#272750</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/272750"><strong>Clinical Synopsis</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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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#history">History</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div style="display: table-cell;">External Links</div>
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</h4>
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" 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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</a>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div><a href="https://clinicaltrials.gov/search?cond=GM2-GANGLIOSIDOSIS, AB VARIANT" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=21360&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK583219/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/8491" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/gm2-activator-deficiency" 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=272750[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><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309246" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</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="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="collapsed 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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<div id="mimVariationLinksFold" 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://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 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/disease/DOID:4795" 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="http://www.informatics.jax.org/disease/272750" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://omia.org/OMIA001427/" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:272750" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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<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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</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> 71253000<br />
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<strong>ORPHA:</strong> 309246<br />
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<strong>DO:</strong> 4795<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="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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272750
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</span>
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</span>
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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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GM2-GANGLIOSIDOSIS, AB VARIANT
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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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|
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<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
HEXOSAMINIDASE ACTIVATOR DEFICIENCY<br />
|
|
GM2 ACTIVATOR DEFICIENCY<br />
|
|
AB VARIANT GM2-GANGLIOSIDOSIS<br />
|
|
TAY-SACHS DISEASE, AB VARIANT
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/683?start=-3&limit=10&highlight=683">
|
|
5q33.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
GM2-gangliosidosis, AB variant
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/272750"> 272750 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
GM2A
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613109"> 613109 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/272750" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/272750" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/272750" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cherry-red macular spots (in most patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2216370&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2216370</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010729" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010729</a>]</span><br /> -
|
|
Roving eye movements <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45339001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45339001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.03</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.53" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.53</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271384&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271384</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Axial hypotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853743&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853743</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Neurodegeneration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027746&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027746</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002180</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002180</a>]</span><br /> -
|
|
Loss of developmental skills <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315686</a>]</span><br /> -
|
|
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
|
|
Increased startle response <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848918&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848918</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002267" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002267</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002267" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002267</a>]</span><br /> -
|
|
Hyperacusis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25289003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25289003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/194399009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">194399009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H93.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H93.23</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/388.42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">388.42</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034880&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034880</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010780" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010780</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010780" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010780</a>]</span><br /> -
|
|
Cognitive decline <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386806002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386806002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0338656&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0338656</a>, <a href="https://bioportal.bioontology.org/search?q=C0234985&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234985</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001268" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001268</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001268" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001268</a>]</span><br /> -
|
|
Loss of speech <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0542223&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0542223</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002371</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002371</a>]</span><br /> -
|
|
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
|
|
Hyperreflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> -
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Spastic quadriparesis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298282001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298282001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0575059&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0575059</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001285" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001285</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001285" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001285</a>]</span><br /> -
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Pyramidal tract signs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14648003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14648003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234132&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234132</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007256</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007256</a>]</span><br /> -
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Dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
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Chorea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271700006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271700006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G25.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G25.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008489&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008489</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002072" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002072</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002072" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002072</a>]</span><br /> -
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Primitive reflexes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246570002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246570002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1838319&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1838319</a>, <a href="https://bioportal.bioontology.org/search?q=C0422895&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0422895</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002476" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002476</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002476" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002476</a>]</span><br /> -
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Cerebral atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span><br /> -
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Brain biopsy shows membranous neuronal cytoplasmic inclusions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315685&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315685</a>]</span><br /> -
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Astrocytic inclusions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315684&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315684</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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</span>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Gm2-ganglioside accumulation in tissues <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315682&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315682</a>]</span><br />
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</span>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Onset in infancy or childhood<br /> -
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Variable severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861403&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861403</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Caused by mutation in the GM2 activator gene (GM2A, <a href="/entry/613109#0001">613109.0001</a>)<br />
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</span>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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<div>
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<br />
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because GM2-gangliosidosis AB variant is caused by homozygous mutation in the GM2A gene (<a href="/entry/613109">613109</a>) on chromosome 5q33.</p>
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<br />
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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<p>The GM2-gangliosidoses are a group of disorders caused by excessive accumulation of ganglioside GM2 and related glycolipids in the lysosomes, mainly of neuronal cells. GM2-gangliosidosis AB variant is characterized by normal hexosaminidase A (HEXA; <a href="/entry/606869">606869</a>) and hexosaminidase B (HEXB; <a href="/entry/606873">606873</a>) but the inability to form a functional GM2 activator complex. The clinical and biochemical phenotype of the AB variant is very similar to that of classic Tay-Sachs disease (see <a href="/entry/272800">272800</a>) (<a href="#5" class="mim-tip-reference" title="Gravel, R. A., Kaback, M. M., Proia, R. L., Sandhoff, K., Suzuki, K., Suzuki, K. <strong>The GM2 gangliosidoses. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. III (8th ed.)</strong> New York: McGraw-Hill (pub.) 2001."None>Gravel et al., 2001</a>).</p>
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<br />
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<a id="clinicalFeatures" class="mim-anchor"></a>
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<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<strong>Clinical Features</strong>
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<p><a href="#12" class="mim-tip-reference" title="Sandhoff, K., Harzer, K., Wassle, W., Jatzkewitz, H. <strong>Enzyme alterations and lipid storage in three variants of Tay-Sachs disease.</strong> J. Neurochem. 18: 2469-2489, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5135907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5135907</a>] [<a href="https://doi.org/10.1111/j.1471-4159.1971.tb00204.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5135907">Sandhoff et al. (1971)</a> referred to Sandhoff disease (<a href="/entry/268800">268800</a>) as variant 0 (since both hexosaminidases A and B are missing) and classic Tay-Sachs disease as variant B (since HEXA is absent but HEXB is present in increased amounts). They studied a single patient with a third form they called variant AB, because both Hex-A and Hex-B are increased in amounts. Sandhoff's patient with the AB variant was studied clinically by Hugo Moser, then of Boston. A brother and sister were affected. In the AB variant, Gm2-ganglioside accumulates as in the other 2 forms despite the presence of both HEXA and HEXB. The patients were French Canadian (<a href="#9" class="mim-tip-reference" title="Phillips, J. A., III. <strong>Personal Communication.</strong> Baltimore, Md. 8/11/1983."None>Phillips, 1983</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5135907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="de Baecque, C. M., Suzuki, K., Rapin, I., Johnson, A. B., Whethers, D. L., Suzuki, K. <strong>GM2-gangliosidosis, AB variant: clinico-pathological study of a case.</strong> Acta Neuropath. (Berlin) 33: 207-226, 1975."None>De Baecque et al. (1975)</a> reported a black female infant with the AB variant of GM2-gangliosidosis. She had normal early development, but showed loss of developmental skills beginning around 9 months of age. At age 12 months, she presented with a prolonged generalized seizure, and was found to have increased startle to sound, hypotonia, and cherry-red macular spots. By age 14 months, she could no longer sit or roll over. Brain biopsy showed neurons and astrocytes with cytoplasmic membranous inclusions of storage material, and HEXA and HEXB were normal.</p><p><a href="#1" class="mim-tip-reference" title="Chen, B., Rigat, B., Curry, C., Mahuran, D. J. <strong>Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2.</strong> Am. J. Hum. Genet. 65: 77-87, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364519</a>] [<a href="https://doi.org/10.1086/302463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364519">Chen et al. (1999)</a> reported a new patient with deficiency of the GM2 activator protein. No consanguinity was identified in the family, but the patient was derived from a geographically isolated, small Laotian hill tribe. The child was thought to be normal until the age of approximately 5 months when he was noted to have delayed motor milestones and increasing weakness. At age 9 months, magnetic resonance imaging showed increased signal density in the periventricular white matter and altered signal density in the basal ganglia. Ophthalmologic evaluation showed bilateral macular cherry red spots. At age 2.5 years, he was evaluated for his neurodegenerative course. The patient was experiencing approximately 3 major motor seizures and hundreds of myoclonic jerks per day. Hyperacusis was extreme, with an exaggerated startle response. Physical examination showed a nondysmorphic, profoundly hypotonic child, who was unresponsive to his environment. Despite normal Hex-A levels in lymphocytes, the clinical diagnosis strongly suggested Tay-Sachs disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10364519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Sakuraba, H., Itoh, K., Shimmoto, M., Utsumi, K., Kase, R., Hashimoto, Y., Ozawa, T., Ohwada, Y., Imataka, G., Eguchi, M., Furukawa, T., Schepers, U., Sandhoff, K. <strong>GM2 gangliosidosis AB variant: clinical and biochemical studies of a Japanese patient.</strong> Neurology 52: 372-377, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9932959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9932959</a>] [<a href="https://doi.org/10.1212/wnl.52.2.372" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9932959">Sakuraba et al. (1999)</a> described complete absence of the GM2 activator protein by Western blot analysis and metabolic studies in a Japanese patient with a progressive neurologic disorder that began with muscular weakness and hypotonia at 1 month of age. The patient later developed a startle reaction, severe psychomotor retardation, and myoclonic seizures. Northern blot analysis demonstrated normal levels of mRNA of the appropriate size, and no mutations were detected in the protein coding region of the GM2 activator gene. The authors speculated that there may be other factors affecting the activity or stability of the GM2 activator. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9932959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Clinical Variability</em></strong></p><p>
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<a href="#11" class="mim-tip-reference" title="Salih, M. A., Seidahmed, M. Z., El Khashab, H. Y., Hamad, M. H. A., Bosley, T. M., Burn, S., Myers, A., Landsverk, M. L., Crotwell, P. L., Bilguvar, K., Mane, S., Kruer, M. C. <strong>Mutation in GM2A leads to a progressive chorea-dementia syndrome.</strong> Tremor Other Hyperkinet. Mov. (N.Y.) 5: 306, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26203402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26203402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26203402[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/10.7916/D8D21WQ0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26203402">Salih et al. (2015)</a> reported 3 patients from a highly consanguineous Saudi family with childhood onset of a neurodegenerative disorder. The patients developed normally until 7 or 8 years of age, at which time they showed some abnormal behavior, including increased anxiety and phobias. Thereafter, all showed loss of developmental skills, including speech, cognition, and motor function. They developed spastic quadriparesis, limb dystonia, pyramidal signs, and generalized chorea. The hyperkinetic disorder gradually gave way to a rigid akinetic state, and all patients lost independent ambulation in the teenage years. Brain imaging showed cortical atrophy; biopsies were not reported. None of the patients had hyperacusis or cherry-red macular spots. Exome sequencing identified a homozygous mutation in the GM2A gene (P55L; <a href="/entry/613109#0006">613109.0006</a>). Functional studies of the variant and studies of patient cells were not performed. <a href="#11" class="mim-tip-reference" title="Salih, M. A., Seidahmed, M. Z., El Khashab, H. Y., Hamad, M. H. A., Bosley, T. M., Burn, S., Myers, A., Landsverk, M. L., Crotwell, P. L., Bilguvar, K., Mane, S., Kruer, M. C. <strong>Mutation in GM2A leads to a progressive chorea-dementia syndrome.</strong> Tremor Other Hyperkinet. Mov. (N.Y.) 5: 306, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26203402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26203402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26203402[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/10.7916/D8D21WQ0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26203402">Salih et al. (2015)</a> noted that the phenotype in this family was milder than that usually observed in patients with this disorder, thus expanding the phenotypic spectrum associated with GM2A mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26203402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 transmission pattern of the AB variant of GM2-gangliosidosis in the family reported by <a href="#11" class="mim-tip-reference" title="Salih, M. A., Seidahmed, M. Z., El Khashab, H. Y., Hamad, M. H. A., Bosley, T. M., Burn, S., Myers, A., Landsverk, M. L., Crotwell, P. L., Bilguvar, K., Mane, S., Kruer, M. C. <strong>Mutation in GM2A leads to a progressive chorea-dementia syndrome.</strong> Tremor Other Hyperkinet. Mov. (N.Y.) 5: 306, 2015. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26203402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26203402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26203402[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/10.7916/D8D21WQ0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26203402">Salih et al. (2015)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26203402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Conzelmann, E., Sandhoff, K. <strong>AB variant of infantile Gm2-gangliosidosis: deficiency of a factor necessary for stimulation of hexosaminidase A-catalyzed degradation of ganglioside Gm2 and glycolipid Ga2.</strong> Proc. Nat. Acad. Sci. 75: 3979-3983, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/99746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">99746</a>] [<a href="https://doi.org/10.1073/pnas.75.8.3979" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="99746">Conzelmann and Sandhoff (1978)</a> showed that an activating factor necessary for the degradation of GM2-ganglioside by HEXA is defective in the AB variant. This activating factor is necessary for the interaction of lipid substrates and the water-soluble hydrolase. The factor is normal in Tay-Sachs and Sandhoff diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=99746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency, <a href="#13" class="mim-tip-reference" title="Schroder, M., Schnabel, D., Suzuki, K., Sandhoff, K. <strong>A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB.</strong> FEBS Lett. 290: 1-3, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1915858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1915858</a>] [<a href="https://doi.org/10.1016/0014-5793(91)81211-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1915858">Schroder et al. (1991)</a> and <a href="#15" class="mim-tip-reference" title="Xie, B., Wang, W., Mahuran, D. J. <strong>A cys138-to-arg substitution in the G-M2 activator protein is associated with the AB variant form of G-M2 gangliosidosis.</strong> Am. J. Hum. Genet. 50: 1046-1052, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1570834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1570834</a>]" pmid="1570834">Xie et al. (1992)</a> identified a homozygous missense mutation in the GM2A gene (C138R; <a href="/entry/613109#0001">613109.0001</a>). The patient was originally reported by <a href="#3" class="mim-tip-reference" title="de Baecque, C. M., Suzuki, K., Rapin, I., Johnson, A. B., Whethers, D. L., Suzuki, K. <strong>GM2-gangliosidosis, AB variant: clinico-pathological study of a case.</strong> Acta Neuropath. (Berlin) 33: 207-226, 1975."None>de Baecque et al. (1975)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1570834+1915858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By RT-PCR of the GM2A gene in a patient with deficiency of GM2-activator protein, <a href="#1" class="mim-tip-reference" title="Chen, B., Rigat, B., Curry, C., Mahuran, D. J. <strong>Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2.</strong> Am. J. Hum. Genet. 65: 77-87, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364519</a>] [<a href="https://doi.org/10.1086/302463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364519">Chen et al. (1999)</a> detected some normal-sized cDNA and a smaller cDNA species, which was not seen in the RT-PCR products from normal controls. Sequencing revealed that although the patient's normal-sized cDNA contained a single nonsense mutation in exon 2, his smaller cDNA was the result of an in-frame deletion of exon 2. Long PCR was used to amplify introns 1 and 2 from the patient and normal genomic DNA, and no differences in size, in 5-prime and 3-prime end sequences, or in restriction-mapping patterns were observed. From these data, <a href="#1" class="mim-tip-reference" title="Chen, B., Rigat, B., Curry, C., Mahuran, D. J. <strong>Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2.</strong> Am. J. Hum. Genet. 65: 77-87, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364519</a>] [<a href="https://doi.org/10.1086/302463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364519">Chen et al. (1999)</a> developed a set of 4 PCR primers that could be used to identify GM2A mutations. With this procedure, they demonstrated that the patient was probably homozygous for a nonsense mutation, glu54 to ter (<a href="/entry/613109#0005">613109.0005</a>). <a href="#1" class="mim-tip-reference" title="Chen, B., Rigat, B., Curry, C., Mahuran, D. J. <strong>Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2.</strong> Am. J. Hum. Genet. 65: 77-87, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364519</a>] [<a href="https://doi.org/10.1086/302463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364519">Chen et al. (1999)</a> pointed to the work of <a href="#4" class="mim-tip-reference" title="Dietz, H. C., Valle, D., Francomano, C. A., Kendzior, R. J., Jr., Pyeritz, R. E., Cutting, G. R. <strong>The skipping of constitutive exons in vivo induced by nonsense mutations.</strong> Science 259: 680-683, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8430317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8430317</a>] [<a href="https://doi.org/10.1126/science.8430317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8430317">Dietz et al. (1993)</a> and of others, indicating that shortened reading frames (i.e., early stop codons) can lead not only to mRNA instability, but also to the in-frame skipping of the constitutive exon in which the mutation is found. They also noted that <a href="#14" class="mim-tip-reference" title="Valentine, C. R., Heflich, R. H. <strong>The association of nonsense mutations with exon-skipping in hprt mRNA of Chinese hamster ovary cells results from an artifact of RT-PCR.</strong> RNA 3: 660-676, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9174100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9174100</a>]" pmid="9174100">Valentine and Heflich (1997)</a>, from a study of the association of nonsense mutations with exon skipping in hprt mRNA of Chinese hamster ovary cells, concluded that the association was the result of an RT-PCR artifact. <a href="#1" class="mim-tip-reference" title="Chen, B., Rigat, B., Curry, C., Mahuran, D. J. <strong>Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2.</strong> Am. J. Hum. Genet. 65: 77-87, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364519</a>] [<a href="https://doi.org/10.1086/302463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364519">Chen et al. (1999)</a> interpreted their results as supporting the conclusion of <a href="#14" class="mim-tip-reference" title="Valentine, C. R., Heflich, R. H. <strong>The association of nonsense mutations with exon-skipping in hprt mRNA of Chinese hamster ovary cells results from an artifact of RT-PCR.</strong> RNA 3: 660-676, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9174100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9174100</a>]" pmid="9174100">Valentine and Heflich (1997)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8430317+10364519+9174100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#7" class="mim-tip-reference" title="Liu, Y., Hoffmann, A., Grinberg, A., Westphal, H., McDonald, M. P., Miller, K. M., Crawley, J. N., Sandhoff, K., Suzuki, K., Proia, R. L. <strong>Mouse model of GM2 activator deficiency manifests cerebellar pathology and motor impairment.</strong> Proc. Nat. Acad. Sci. 94: 8138-8143, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9223328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9223328</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9223328[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.94.15.8138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9223328">Liu et al. (1997)</a> generated mice with a disrupted Gm2a gene as a model; knockout mouse models for Tay-Sachs and Sandhoff disease had previously been studied. Mice with disruption of the Hexa gene (the Tay-Sachs disease model) were asymptomatic, whereas those with absence of Hexb (the Sandhoff disease model) were severely affected. The mice with disruption of Gm2a demonstrated neuronal storage, but only in restricted regions of the brain, reminiscent of the asymptomatic Tay-Sachs model mice. However, unlike the Tay-Sachs mice, the Gm2a -/- mice displayed significant storage in the cerebellum and defects in balance and coordination. The abnormal ganglioside storage in these mice consisted of GM2 with a low amount of GA2. Their results demonstrated that the activator protein is required for GM2 degradation and also may indicate a role for GM2 activator in GA2 degradation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9223328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#8" class="mim-tip-reference" title="O'Neill, B., Butler, A. B., Young, E., Falk, P. M., Bass, N. H. <strong>Adult-onset Gm2-gangliosidosis: seizures, dementia, and normal pressure hydrocephalus associated with glycolipid storage in the brain and arachnoid granulation.</strong> Neurology 28: 1117-1123, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/568730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">568730</a>] [<a href="https://doi.org/10.1212/wnl.28.11.1117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="568730">O'Neill et al. (1978)</a> described a 22-year-old non-Jewish female who, although slow in school, had no recognized neurologic abnormality until age 18 when seizures began. They considered this an adult-onset form of the AB variant of GM2-gangliosidosis. However, <a href="#5" class="mim-tip-reference" title="Gravel, R. A., Kaback, M. M., Proia, R. L., Sandhoff, K., Suzuki, K., Suzuki, K. <strong>The GM2 gangliosidoses. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. III (8th ed.)</strong> New York: McGraw-Hill (pub.) 2001."None>Gravel et al. (2001)</a> concluded that this was most likely not a case of the AB variant because the brain gangliosides showed only minor relative increases of monosialogangliosides, a highly nonspecific finding seen in many neurodegenerative disorders, and because no evidence of impaired GM2 ganglioside degradation was provided. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=568730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#Hechtman1982" class="mim-tip-reference" title="Hechtman, P., Gordon, B. A., Ng Ying Kin, N. M. K. <strong>Deficiency of the hexosaminidase A activator protein in a case of GM2 gangliosidosis; variant AB.</strong> Pediat. Res. 16: 217-222, 1982.">Hechtman et al. (1982)</a>
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[<a href="https://doi.org/10.1086/302463" target="_blank">Full Text</a>]
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<a id="Conzelmann1978" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1073/pnas.75.8.3979" target="_blank">Full Text</a>]
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Science 259: 680-683, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8430317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8430317</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8430317" 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/10.1126/science.8430317" target="_blank">Full Text</a>]
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<a id="Gravel2001" class="mim-anchor"></a>
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Gravel, R. A., Kaback, M. M., Proia, R. L., Sandhoff, K., Suzuki, K., Suzuki, K.
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<strong>The GM2 gangliosidoses. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. III (8th ed.)</strong>
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New York: McGraw-Hill (pub.) 2001.
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Hechtman, P., Gordon, B. A., Ng Ying Kin, N. M. K.
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<strong>Deficiency of the hexosaminidase A activator protein in a case of GM2 gangliosidosis; variant AB.</strong>
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Pediat. Res. 16: 217-222, 1982.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6801612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6801612</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6801612" 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/10.1203/00006450-198203000-00011" target="_blank">Full Text</a>]
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Liu, Y., Hoffmann, A., Grinberg, A., Westphal, H., McDonald, M. P., Miller, K. M., Crawley, J. N., Sandhoff, K., Suzuki, K., Proia, R. L.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9223328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9223328</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9223328[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9223328" 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.94.15.8138" target="_blank">Full Text</a>]
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<a id="O'Neill1978" class="mim-anchor"></a>
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<p class="mim-text-font">
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O'Neill, B., Butler, A. B., Young, E., Falk, P. M., Bass, N. H.
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<strong>Adult-onset Gm2-gangliosidosis: seizures, dementia, and normal pressure hydrocephalus associated with glycolipid storage in the brain and arachnoid granulation.</strong>
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Neurology 28: 1117-1123, 1978.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/568730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">568730</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=568730" 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.28.11.1117" target="_blank">Full Text</a>]
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<a id="Phillips1983" class="mim-anchor"></a>
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<strong>Personal Communication.</strong>
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Baltimore, Md. 8/11/1983.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9932959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9932959</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9932959" 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.52.2.372" target="_blank">Full Text</a>]
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Salih, M. A., Seidahmed, M. Z., El Khashab, H. Y., Hamad, M. H. A., Bosley, T. M., Burn, S., Myers, A., Landsverk, M. L., Crotwell, P. L., Bilguvar, K., Mane, S., Kruer, M. C.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26203402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26203402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26203402[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26203402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1471-4159.1971.tb00204.x" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9174100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9174100</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9174100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Xie, B., Wang, W., Mahuran, D. J.
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<strong>A cys138-to-arg substitution in the G-M2 activator protein is associated with the AB variant form of G-M2 gangliosidosis.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1570834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1570834</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1570834" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Cassandra L. Kniffin - updated : 7/6/2016
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<span class="mim-text-font">
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Victor A. McKusick - updated : 6/28/1999<br>Orest Hurko - updated : 3/22/1999<br>Victor A. McKusick - updated : 9/2/1997
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Creation Date:
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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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Victor A. McKusick : 6/24/1986
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carol : 06/04/2019
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carol : 07/20/2016<br>carol : 07/18/2016<br>carol : 7/9/2016<br>ckniffin : 7/6/2016<br>terry : 11/5/2009<br>carol : 11/4/2009<br>terry : 11/4/2009<br>carol : 11/3/2009<br>carol : 11/2/2009<br>carol : 1/21/2008<br>terry : 4/21/2005<br>alopez : 3/17/2004<br>carol : 7/9/1999<br>jlewis : 7/7/1999<br>terry : 6/28/1999<br>carol : 3/22/1999<br>carol : 5/20/1998<br>jenny : 12/3/1997<br>jenny : 9/9/1997<br>terry : 9/2/1997<br>terry : 12/30/1996<br>terry : 12/19/1996<br>mark : 6/16/1995<br>carol : 1/18/1995<br>warfield : 4/20/1994<br>mimadm : 3/29/1994<br>carol : 12/13/1993<br>carol : 11/30/1993
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<span class="mim-font">
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<strong>#</strong> 272750
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</h3>
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GM2-GANGLIOSIDOSIS, AB VARIANT
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<em>Alternative titles; symbols</em>
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HEXOSAMINIDASE ACTIVATOR DEFICIENCY<br />
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GM2 ACTIVATOR DEFICIENCY<br />
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AB VARIANT GM2-GANGLIOSIDOSIS<br />
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TAY-SACHS DISEASE, AB VARIANT
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<strong>SNOMEDCT:</strong> 71253000;
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<strong>ORPHA:</strong> 309246;
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<strong>DO:</strong> 4795;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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5q33.1
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GM2-gangliosidosis, AB variant
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<span class="mim-font">
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272750
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Autosomal recessive
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<span class="mim-font">
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3
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GM2A
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<span class="mim-font">
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613109
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<strong>TEXT</strong>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because GM2-gangliosidosis AB variant is caused by homozygous mutation in the GM2A gene (613109) on chromosome 5q33.</p>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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<p>The GM2-gangliosidoses are a group of disorders caused by excessive accumulation of ganglioside GM2 and related glycolipids in the lysosomes, mainly of neuronal cells. GM2-gangliosidosis AB variant is characterized by normal hexosaminidase A (HEXA; 606869) and hexosaminidase B (HEXB; 606873) but the inability to form a functional GM2 activator complex. The clinical and biochemical phenotype of the AB variant is very similar to that of classic Tay-Sachs disease (see 272800) (Gravel et al., 2001).</p>
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<strong>Clinical Features</strong>
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<p>Sandhoff et al. (1971) referred to Sandhoff disease (268800) as variant 0 (since both hexosaminidases A and B are missing) and classic Tay-Sachs disease as variant B (since HEXA is absent but HEXB is present in increased amounts). They studied a single patient with a third form they called variant AB, because both Hex-A and Hex-B are increased in amounts. Sandhoff's patient with the AB variant was studied clinically by Hugo Moser, then of Boston. A brother and sister were affected. In the AB variant, Gm2-ganglioside accumulates as in the other 2 forms despite the presence of both HEXA and HEXB. The patients were French Canadian (Phillips, 1983). </p><p>De Baecque et al. (1975) reported a black female infant with the AB variant of GM2-gangliosidosis. She had normal early development, but showed loss of developmental skills beginning around 9 months of age. At age 12 months, she presented with a prolonged generalized seizure, and was found to have increased startle to sound, hypotonia, and cherry-red macular spots. By age 14 months, she could no longer sit or roll over. Brain biopsy showed neurons and astrocytes with cytoplasmic membranous inclusions of storage material, and HEXA and HEXB were normal.</p><p>Chen et al. (1999) reported a new patient with deficiency of the GM2 activator protein. No consanguinity was identified in the family, but the patient was derived from a geographically isolated, small Laotian hill tribe. The child was thought to be normal until the age of approximately 5 months when he was noted to have delayed motor milestones and increasing weakness. At age 9 months, magnetic resonance imaging showed increased signal density in the periventricular white matter and altered signal density in the basal ganglia. Ophthalmologic evaluation showed bilateral macular cherry red spots. At age 2.5 years, he was evaluated for his neurodegenerative course. The patient was experiencing approximately 3 major motor seizures and hundreds of myoclonic jerks per day. Hyperacusis was extreme, with an exaggerated startle response. Physical examination showed a nondysmorphic, profoundly hypotonic child, who was unresponsive to his environment. Despite normal Hex-A levels in lymphocytes, the clinical diagnosis strongly suggested Tay-Sachs disease. </p><p>Sakuraba et al. (1999) described complete absence of the GM2 activator protein by Western blot analysis and metabolic studies in a Japanese patient with a progressive neurologic disorder that began with muscular weakness and hypotonia at 1 month of age. The patient later developed a startle reaction, severe psychomotor retardation, and myoclonic seizures. Northern blot analysis demonstrated normal levels of mRNA of the appropriate size, and no mutations were detected in the protein coding region of the GM2 activator gene. The authors speculated that there may be other factors affecting the activity or stability of the GM2 activator. </p><p><strong><em>Clinical Variability</em></strong></p><p>
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Salih et al. (2015) reported 3 patients from a highly consanguineous Saudi family with childhood onset of a neurodegenerative disorder. The patients developed normally until 7 or 8 years of age, at which time they showed some abnormal behavior, including increased anxiety and phobias. Thereafter, all showed loss of developmental skills, including speech, cognition, and motor function. They developed spastic quadriparesis, limb dystonia, pyramidal signs, and generalized chorea. The hyperkinetic disorder gradually gave way to a rigid akinetic state, and all patients lost independent ambulation in the teenage years. Brain imaging showed cortical atrophy; biopsies were not reported. None of the patients had hyperacusis or cherry-red macular spots. Exome sequencing identified a homozygous mutation in the GM2A gene (P55L; 613109.0006). Functional studies of the variant and studies of patient cells were not performed. Salih et al. (2015) noted that the phenotype in this family was milder than that usually observed in patients with this disorder, thus expanding the phenotypic spectrum associated with GM2A mutations. </p>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</h4>
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<span class="mim-text-font">
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<p>The transmission pattern of the AB variant of GM2-gangliosidosis in the family reported by Salih et al. (2015) was consistent with autosomal recessive inheritance. </p>
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</span>
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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>Pathogenesis</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Conzelmann and Sandhoff (1978) showed that an activating factor necessary for the degradation of GM2-ganglioside by HEXA is defective in the AB variant. This activating factor is necessary for the interaction of lipid substrates and the water-soluble hydrolase. The factor is normal in Tay-Sachs and Sandhoff diseases. </p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency, Schroder et al. (1991) and Xie et al. (1992) identified a homozygous missense mutation in the GM2A gene (C138R; 613109.0001). The patient was originally reported by de Baecque et al. (1975). </p><p>By RT-PCR of the GM2A gene in a patient with deficiency of GM2-activator protein, Chen et al. (1999) detected some normal-sized cDNA and a smaller cDNA species, which was not seen in the RT-PCR products from normal controls. Sequencing revealed that although the patient's normal-sized cDNA contained a single nonsense mutation in exon 2, his smaller cDNA was the result of an in-frame deletion of exon 2. Long PCR was used to amplify introns 1 and 2 from the patient and normal genomic DNA, and no differences in size, in 5-prime and 3-prime end sequences, or in restriction-mapping patterns were observed. From these data, Chen et al. (1999) developed a set of 4 PCR primers that could be used to identify GM2A mutations. With this procedure, they demonstrated that the patient was probably homozygous for a nonsense mutation, glu54 to ter (613109.0005). Chen et al. (1999) pointed to the work of Dietz et al. (1993) and of others, indicating that shortened reading frames (i.e., early stop codons) can lead not only to mRNA instability, but also to the in-frame skipping of the constitutive exon in which the mutation is found. They also noted that Valentine and Heflich (1997), from a study of the association of nonsense mutations with exon skipping in hprt mRNA of Chinese hamster ovary cells, concluded that the association was the result of an RT-PCR artifact. Chen et al. (1999) interpreted their results as supporting the conclusion of Valentine and Heflich (1997). </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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<span class="mim-text-font">
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<p>Liu et al. (1997) generated mice with a disrupted Gm2a gene as a model; knockout mouse models for Tay-Sachs and Sandhoff disease had previously been studied. Mice with disruption of the Hexa gene (the Tay-Sachs disease model) were asymptomatic, whereas those with absence of Hexb (the Sandhoff disease model) were severely affected. The mice with disruption of Gm2a demonstrated neuronal storage, but only in restricted regions of the brain, reminiscent of the asymptomatic Tay-Sachs model mice. However, unlike the Tay-Sachs mice, the Gm2a -/- mice displayed significant storage in the cerebellum and defects in balance and coordination. The abnormal ganglioside storage in these mice consisted of GM2 with a low amount of GA2. Their results demonstrated that the activator protein is required for GM2 degradation and also may indicate a role for GM2 activator in GA2 degradation. </p>
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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>History</strong>
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</span>
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</div>
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<span class="mim-text-font">
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<p>O'Neill et al. (1978) described a 22-year-old non-Jewish female who, although slow in school, had no recognized neurologic abnormality until age 18 when seizures began. They considered this an adult-onset form of the AB variant of GM2-gangliosidosis. However, Gravel et al. (2001) concluded that this was most likely not a case of the AB variant because the brain gangliosides showed only minor relative increases of monosialogangliosides, a highly nonspecific finding seen in many neurodegenerative disorders, and because no evidence of impaired GM2 ganglioside degradation was provided. </p>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Hechtman et al. (1982)
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</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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<ol>
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<li>
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<p class="mim-text-font">
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Chen, B., Rigat, B., Curry, C., Mahuran, D. J.
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<strong>Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2.</strong>
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Am. J. Hum. Genet. 65: 77-87, 1999.
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[PubMed: 10364519]
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[Full Text: https://doi.org/10.1086/302463]
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</p>
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<li>
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<p class="mim-text-font">
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Conzelmann, E., Sandhoff, K.
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<strong>AB variant of infantile Gm2-gangliosidosis: deficiency of a factor necessary for stimulation of hexosaminidase A-catalyzed degradation of ganglioside Gm2 and glycolipid Ga2.</strong>
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Proc. Nat. Acad. Sci. 75: 3979-3983, 1978.
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[PubMed: 99746]
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[Full Text: https://doi.org/10.1073/pnas.75.8.3979]
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</p>
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<li>
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<p class="mim-text-font">
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de Baecque, C. M., Suzuki, K., Rapin, I., Johnson, A. B., Whethers, D. L., Suzuki, K.
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<strong>GM2-gangliosidosis, AB variant: clinico-pathological study of a case.</strong>
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Acta Neuropath. (Berlin) 33: 207-226, 1975.
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</p>
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</li>
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<li>
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