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Entry
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- #252650 - MUCOLIPIDOSIS IV; ML4
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- OMIM
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<p>
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<span class="h4">#252650</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/252650"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
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<a href="/phenotypicSeries/PS256550"> <strong>Phenotypic Series</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="#biochemicalFeatures">Biochemical Features</a>
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<a href="#otherFeatures">Other Features</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#mapping">Mapping</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#history">History</a>
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<a href="#animalModel">Animal Model</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="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<div style="display: table-row">
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<div style="display: table-cell;">External Links</div>
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</a>
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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 id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=MUCOLIPIDOSIS IV" 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=29&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/NBK1214/" 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/4910" 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/mucolipidosis-type-iv" 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=252650[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=578" 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><a href="https://www.possumcore.com/nuxeo/nxdoc/default/f4c86fde-e141-4c27-99b2-ba3f8af56fa0/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0080490" 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/252650" 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://wormbase.org/resources/disease/DOID:0080490" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</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:252650" 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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</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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</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> 725296006<br />
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<strong>ICD10CM:</strong> E75.11<br />
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<strong>ORPHA:</strong> 578<br />
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<strong>DO:</strong> 0080490<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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252650
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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MUCOLIPIDOSIS IV; ML4
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</span>
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</h3>
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</div>
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<div>
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<br />
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ML IV<br />
|
|
SIALOLIPIDOSIS
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
|
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|
</div>
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|
|
|
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<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/19/206?start=-3&limit=10&highlight=206">
|
|
19p13.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Mucolipidosis IV
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/252650"> 252650 </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">
|
|
MCOLN1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605248"> 605248 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/252650" 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">
|
|
|
|
<a href="/phenotypicSeries/PS256550" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', '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/252650" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/252650" 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> Head </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Microcephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Corneal clouding <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64634000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64634000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413921009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413921009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95735008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95735008</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/371.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">371.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0521719&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521719</a>, <a href="https://bioportal.bioontology.org/search?q=C0010038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007957" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007957</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007957" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007957</a>]</span><br /> -
|
|
Corneal opacities <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64634000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64634000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413921009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413921009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/371.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">371.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007957" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007957</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007957" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007957</a>]</span><br /> -
|
|
Fibrous dysplasia of the cornea <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854887&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854887</a>]</span><br /> -
|
|
Progressive retinal degeneration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854888</a>]</span><br /> -
|
|
Optic atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br /> -
|
|
Photophobia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409668002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409668002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246622003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246622003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.14" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.14</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085636</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000613" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000613</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000613" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000613</a>]</span><br /> -
|
|
Strabismus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22066006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22066006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038379</a>, <a href="https://bioportal.bioontology.org/search?q=C2020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2020541</a>, <a href="https://bioportal.bioontology.org/search?q=C1423541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1423541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span><br /> -
|
|
Decreased electroretinogram (ERG) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836859&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836859</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000654" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000654</a>]</span><br />
|
|
|
|
</span>
|
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> ABDOMEN </strong>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Achlorhydria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/47481007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">47481007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20754004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20754004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K31.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K31.83</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/536.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">536.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0001075&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0001075</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032448" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032448</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032448" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032448</a>]</span><br />
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</span>
|
|
</div>
|
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</div>
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</div>
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- 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 /> -
|
|
Slowly progressive neurologic deterioration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854880&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854880</a>]</span><br /> -
|
|
Spastic quadriplegia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/192965001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">192965001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426970&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426970</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002510</a>]</span><br /> -
|
|
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 /> -
|
|
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 /> -
|
|
Extensor plantar responses <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246586009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246586009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366575004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366575004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034935</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span><br /> -
|
|
Delayed psychomotor development (stops at development levels of 1-2 years) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854881&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854881</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
|
|
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
|
|
Lack of language development <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854882&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854882</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001344</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001344</a>]</span><br /> -
|
|
Never able to walk <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854883&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854883</a>]</span><br /> -
|
|
Dysplastic corpus callosum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0431369&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0431369</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006989" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006989</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006989" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006989</a>]</span><br /> -
|
|
Dysmyelination of the brain <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854885&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854885</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007266</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007266</a>]</span><br /> -
|
|
Cerebellar atrophy in older patients <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854886&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854886</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Skin fibroblasts contain cytoplasmic membrane-bound granular inclusions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854889</a>]</span><br /> -
|
|
Cytoplasmic lamellar concentric inclusions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854890&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854890</a>]</span><br /> -
|
|
Inclusions contain phospholipids, phosphatidylcholine, sphingolipids, gangliosides, mucopolysaccharides <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854891&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854891</a>]</span><br /> -
|
|
Normal lysosomal hydrolases <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854892&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854892</a>]</span><br /> -
|
|
Increased serum gastrin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0858520&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0858520</a>]</span><br /> -
|
|
Increased urinary phospholipids <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854893&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854893</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
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|
|
</div>
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|
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset in first year of life <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br /> -
|
|
Increased frequency in Ashkenazi Jewish population (1/100 are carriers)<br />
|
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|
|
</span>
|
|
</div>
|
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</div>
|
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
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<strong> MOLECULAR BASIS </strong>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Caused by mutations in the mucolipin-1 gene (MCOLN1, <a href="/entry/605248#0001">605248.0001</a>)<br />
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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<h5>
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Mucolipidosis
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- <a href="/phenotypicSeries/PS256550">PS256550</a>
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- 6 Entries
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</h5>
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<table class="table table-bordered table-condensed table-hover mim-table-padding">
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<strong>Location</strong>
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
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<strong>Phenotype</strong>
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<strong>Inheritance</strong>
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<strong>Phenotype<br />mapping key</strong>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Phenotype<br />MIM number</strong>
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<strong>Gene/Locus</strong>
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<strong>Gene/Locus<br />MIM number</strong>
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<tbody>
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<td>
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<span class="mim-font">
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<a href="/geneMap/6/339?start=-3&limit=10&highlight=339"> 6p21.33 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/256550"> Sialidosis, type I </a>
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</span>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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<span class="mim-font">
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<a href="/entry/256550"> 256550 </a>
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<span class="mim-font">
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<a href="/entry/608272"> NEU1 </a>
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<span class="mim-font">
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<a href="/entry/608272"> 608272 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/6/339?start=-3&limit=10&highlight=339"> 6p21.33 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/256550"> Sialidosis, type II </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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<span class="mim-font">
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<a href="/entry/256550"> 256550 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/608272"> NEU1 </a>
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<td>
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<span class="mim-font">
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<a href="/entry/608272"> 608272 </a>
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</span>
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</td>
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<tr>
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<span class="mim-font">
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<a href="/geneMap/12/731?start=-3&limit=10&highlight=731"> 12q23.2 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/252600"> Mucolipidosis III alpha/beta </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/252600"> 252600 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607840"> GNPTAB </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607840"> 607840 </a>
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</span>
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</td>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/12/731?start=-3&limit=10&highlight=731"> 12q23.2 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/252500"> Mucolipidosis II alpha/beta </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/252500"> 252500 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607840"> GNPTAB </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607840"> 607840 </a>
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</span>
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</td>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/16/59?start=-3&limit=10&highlight=59"> 16p13.3 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/252605"> Mucolipidosis III gamma </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/252605"> 252605 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607838"> GNPTG </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607838"> 607838 </a>
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</span>
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</td>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/19/206?start=-3&limit=10&highlight=206"> 19p13.2 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/252650"> Mucolipidosis IV </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/252650"> 252650 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/605248"> MCOLN1 </a>
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/605248"> 605248 </a>
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</span>
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</td>
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</table>
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<div class="text-right small">
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
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<br />
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<div>
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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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</span>
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</span>
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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 mucolipidosis IV (ML4) is caused by homozygous or compound heterozygous mutation in the MCOLN1 gene (<a href="/entry/605248">605248</a>) on chromosome 19p13.</p>
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<br />
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<div>
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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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</span>
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</h4>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Mucolipidosis IV (ML4) is an autosomal recessive neurodegenerative lysosomal storage disorder characterized by psychomotor retardation and ophthalmologic abnormalities. The lysosomal hydrolases in ML IV are normal, in contrast to most other storage diseases. The disorder results from a defect in transport along the lysosomal pathway, affecting membrane sorting and/or late steps of endocytosis, which causes intracellular accumulation of lysosomal substrates. Over 80% of the patients in whom the diagnosis of ML IV has been made are Ashkenazi Jews, including severely affected and mildly affected patients (summary by <a href="#10" class="mim-tip-reference" title="Chen, C.-S., Bach, G., Pagano, R. E. <strong>Abnormal transport along the lysosomal pathway in mucolipidosis, type IV disease.</strong> Proc. Nat. Acad. Sci. 95: 6373-6378, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9600972[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.95.11.6373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600972">Chen et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600972" 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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<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 id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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<p><a href="#8" class="mim-tip-reference" title="Berman, E. R., Livni, N., Shapira, E., Merin, S., Levij, I. S. <strong>Congenital corneal clouding with abnormal systemic storage bodies: a new variant of mucolipidosis.</strong> J. Pediat. 84: 519-526, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4365943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4365943</a>] [<a href="https://doi.org/10.1016/s0022-3476(74)80671-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4365943">Berman et al. (1974)</a> reported an Ashkenazi Jewish infant with congenital corneal clouding and abnormal systemic storage bodies. Lysosomal hydrolases were normal. The disorder was characterized as a new variant of mucolipidosis because electron microscopy showed lysosomal storage of lipids together with water-soluble granulated substances. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4365943" 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="#24" class="mim-tip-reference" title="Merin, S., Livni, N., Berman, E. R., Yatziv, S. <strong>Mucolipidosis IV: ocular, systemic, and ultrastructural findings.</strong> Invest. Ophthal. 14: 437-448, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/166049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">166049</a>]" pmid="166049">Merin et al. (1975)</a> described a disorder, termed mucolipidosis IV, in 4 unrelated children of Ashkenazi extraction traced to southern Poland. There were 3 females and 1 male. The most prominent clinical feature was corneal clouding from birth or early infancy, which was the presenting symptom in 2, followed by psychomotor retardation apparent by the end of the first year of life. Skeletal dysplasia, facial dysmorphism, and hepatosplenomegaly were absent. Conjunctival biopsies showed 2 types of abnormal fibroblast inclusion bodies: single-membrane-limited cytoplasmic vacuoles containing both fibrillogranular material and membranous lamellae, and lamellar and concentric bodies resembling those of Tay-Sachs disease (<a href="/entry/272800">272800</a>). Electroretinogram (ERG) performed in 1 patient was subnormal. The disorder was characterized as a mucolipidosis because electron microscopy showed lysosomal storage of lipids together with water-soluble granulated substances. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=166049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#33" class="mim-tip-reference" title="Tellez-Nagel, I., Rapin, I., Iwamoto, T., Johnson, A. B., Norton, W. T., Nitowsky, H. <strong>Mucolipidosis IV: clinical, ultrastructural, histochemical, and chemical studies of a case, including a brain biopsy.</strong> Arch. Neurol. 33: 828-835, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/187156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">187156</a>] [<a href="https://doi.org/10.1001/archneur.1976.00500120032005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="187156">Tellez-Nagel et al. (1976)</a> reported a 7-year-old Ashkenazi Jewish boy who showed developmental regression at age 8 months. Corneal, conjunctival, and cerebral biopsies showed lipid-like and mucopolysaccharide-like concentric membranous lamellar lysosomal inclusions which were reminiscent of those found in the gangliosidoses. In the brain, dense fluorescent inclusions resembled those in ceroid-lipofuscinosis (see, e.g., <a href="/entry/256730">256730</a>). Total ganglioside content of the white matter was increased, but the pattern was normal. The findings were consistent with ML IV. <a href="#21" class="mim-tip-reference" title="Goutieres, F., Arsenio-Nunes, M.-L., Aicardi, J. <strong>Mucolipidosis IV.</strong> Neuropadiatrie 10: 321-330, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/231746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">231746</a>] [<a href="https://doi.org/10.1055/s-0028-1085335" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="231746">Goutieres et al. (1979)</a> described 5 cases of mucolipidosis IV in non-Jews. Four patients were in 2 sibships. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=231746+187156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Crandall, B. F., Philippart, M., Brown, W. J., Bluestone, D. A. <strong>Mucolipidosis IV.</strong> Am. J. Med. Genet. 12: 301-308, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7114093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7114093</a>] [<a href="https://doi.org/10.1002/ajmg.1320120308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7114093">Crandall et al. (1982)</a> reported a 2-year-old Ashkenazi Jewish girl who presented with developmental delay and microcephaly. Photophobia and corneal haze were noted at 9 months of age, and fibrous dysplasia and corneal opacities were found at 18 months. At 2 years, she had esotropia, mild coarse facies, and hypotonia, and was unable to walk or speak. Examination at 5 years showed neurologic progression of the disorder, with hoarse cry, nystagmus, truncal titubation, spasticity, dystonic posturing, hyperreflexia, and extensor plantar responses. She was unable to sit without support and did not respond to visual stimuli. There was no organomegaly, and urine analysis showed no oligosaccharide or mucopolysaccharide excretion. Electron microscopy showed cytoplasmic granular inclusions and concentric lamellar structures in liver, muscle, and nerve. Phospholipids were increased in liver, skin fibroblasts, and urine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7114093" 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="#9" class="mim-tip-reference" title="Caimi, L., Tettamanti, G., Berra, B., Sale, F. O., Borrone, C., Gatti, R., Durand, P., Martin, J. J. <strong>Mucolipidosis IV, a sialolipidosis due to ganglioside sialidase deficiency.</strong> J. Inherit. Metab. Dis. 5: 218-224, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6820444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6820444</a>] [<a href="https://doi.org/10.1007/BF02179146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6820444">Caimi et al. (1982)</a> reported a 22-year-old Italian woman with cloudy corneae, capsular lens opacities, and severe and progressive mental and motor deterioration. Ultrastructural skin biopsy showed membranous cytoplasmic bodies in Schwann cells, vessel walls, fibroblasts, smooth muscle fibers, and sweat glands. There was a complete deficiency of ganglioside sialidase. Urine analysis showed accumulation of all phospholipid species, of several glycolipids, and of gangliosides. <a href="#9" class="mim-tip-reference" title="Caimi, L., Tettamanti, G., Berra, B., Sale, F. O., Borrone, C., Gatti, R., Durand, P., Martin, J. J. <strong>Mucolipidosis IV, a sialolipidosis due to ganglioside sialidase deficiency.</strong> J. Inherit. Metab. Dis. 5: 218-224, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6820444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6820444</a>] [<a href="https://doi.org/10.1007/BF02179146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6820444">Caimi et al. (1982)</a> suggested that ML IV could be called sialolipidosis to distinguish it from sialidosis (<a href="/entry/256550">256550</a>), in which the sialidase (neuraminidase) for glycoprotein and water-soluble oligosaccharides is deficient. They noted that ML IV heterozygotes show partial deficiency of ganglioside sialidase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6820444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Amir, N., Zlotogora, J., Bach, G. <strong>Mucolipidosis type IV: clinical spectrum and natural history.</strong> Pediatrics 79: 953-959, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2438637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2438637</a>]" pmid="2438637">Amir et al. (1987)</a> reported heterogeneity in ophthalmologic features in 20 ML IV patients who ranged in age from 2 to 17 years, noting differences in age at onset and in degree and clinical course of corneal opacities and retinal involvement. One patient, aged 5, had no corneal opacity although her vision was greatly reduced because of severe myopia and retinal degeneration. On the other hand, corneal opacities were congenital in 11 of the 20 cases. All patients had psychomotor retardation and visual impairment during the first year of life. The maximal developmental level achieved was 12 to 15 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2438637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Chitayat, D., Meunier, C. M., Hodgkinson, K. A., Silver, K., Flanders, M., Anderson, I. J., Little, J. M., Whiteman, D. A. H., Carpenter, S. <strong>Mucolipidosis type IV: clinical manifestations and natural history.</strong> Am. J. Med. Genet. 41: 313-318, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1789285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1789285</a>] [<a href="https://doi.org/10.1002/ajmg.1320410310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1789285">Chitayat et al. (1991)</a> reported 5 patients with ML IV from 3 Ashkenazi Jewish families. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus. None progressed beyond the developmental age of 15 months. In 1 patient, death was due to aspiration at age 17 years; the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and was 32 years old at the time of report. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1789285" 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="#6" class="mim-tip-reference" title="Bargal, R., Bach, G. <strong>Mucolipidosis type IV: abnormal transport of lipids to lysosomes.</strong> J. Inherit. Metab. Dis. 20: 625-632, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9323557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9323557</a>] [<a href="https://doi.org/10.1023/a:1005362123443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9323557">Bargal and Bach (1997)</a> observed that even more severely affected ML IV patients, despite an early age at onset, showed very slow or hardly any deterioration in the clinical picture for the first 2 to 3 decades of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9323557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 14 of 15 ML IV patients, <a href="#17" class="mim-tip-reference" title="Frei, K. P., Patronas, N. J., Cruchfield, K. E., Altarescu, G., Schiffmann, R. <strong>Mucolipidosis type IV: characteristic MRI findings.</strong> Neurology 51: 565-569, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9710036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9710036</a>] [<a href="https://doi.org/10.1212/wnl.51.2.565" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9710036">Frei et al. (1998)</a> found a hypoplastic corpus callosum with absent rostrum and a dysplastic or absent splenium, dysmyelinating white matter abnormalities, and increased ferritin deposits in the thalamus and basal ganglia. Atrophy of the cerebellum and cerebrum was observed in older patients, reflecting disease progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9710036" 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="#27" class="mim-tip-reference" title="Pradhan, S. M., Atchaneeyasakul, L.-O., Appukuttan, B., Mixon, R. N., McFarland, T. J., Billingslea, A. M., Wilson, D. J., Stout, J. T., Weleber, R. G. <strong>Electronegative electroretinogram in mucolipidosis IV.</strong> Arch. Ophthal. 120: 45-50, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11786056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11786056</a>] [<a href="https://doi.org/10.1001/archopht.120.1.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11786056">Pradhan et al. (2002)</a> presented the progression of ERG findings in 2 patients with mucolipidosis IV. Both patients showed greater loss of b-wave than a-wave responses. In both, rod-mediated responses were minimal, cone-mediated responses were severely subnormal, and cone b-wave implicit times were prolonged. The electronegative ERG configuration suggested that the primary retinal disturbance in mucolipidosis IV might occur at or proximal to the photoreceptor terminals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11786056" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Goldin, E., Stahl, S., Cooney, A. M., Kaneski, C. R., Gupta, S., Brady, R. O., Ellis, J. R., Schiffmann, R. <strong>Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV.</strong> Hum. Mutat. 24: 460-465, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523648</a>] [<a href="https://doi.org/10.1002/humu.20094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15523648">Goldin et al. (2004)</a> reported a 4-year-old Canadian girl of English and Scottish ancestry with ML IV. She exhibited developmental delay, hypotonia, ataxia, central corneal clouding, and mild photophobia as a relatively moderate phenotype. No organomegaly was present. She walked only with a walker. She was without speech but used about 20 signs to communicate with her parents. She also was able to feed herself with her fingers. Skin biopsy showed membrane-bound osmiophilic lysosomal inclusions. She was compound heterozygous for 2 mutations in the MCOLN1 gene only 1 of which, inherited from the father, was expressed (see <a href="/entry/605248#0007">605248.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15523648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Dobrovolny, R., Liskova, P., Ledvinova, J., Poupetova, H., Asfaw, B., Filipec, M., Jirsova, K., Kraus, J., Elleder, M. <strong>Mucolipidosis IV: report of a case with ocular restricted phenotype caused by leaky splice mutation.</strong> Am. J. Ophthal. 143: 663-671, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17239335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17239335</a>] [<a href="https://doi.org/10.1016/j.ajo.2006.11.049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17239335">Dobrovolny et al. (2007)</a> reported an usually mild case of ML IV. The patient was a girl, not of Ashkenazi Jewish origin, who developed corneal cloudiness at age 2 years. She later developed progressive decreased visual acuity, corneal abrasions, and strabismus. At age 12 years, she showed retinal pigment abnormalities in the macula and retinal vessel attenuation. VEP and ERP examinations were consistent with bilateral retinal dystrophy. Ultrastructural examination showed storage lysosomes filled with either concentric membranes or lucent precipitate in corneal and conjunctival epithelia and vascular endothelium. There was also evidence of gastric parietal cell involvement leading to a compensatory increase in gastrin production. Otherwise, the patient had normal psychomotor development and no neurologic abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17239335" 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="#16" class="mim-tip-reference" title="Folkerth, R. D., Alroy, J., Lomakina, I., Skutelsky, E., Raghavan, S. S., Kolodny, E. H. <strong>Mucolipidosis IV: morphology and histochemistry of an autopsy case.</strong> J. Neuropath. Exp. Neurol. 54: 154-164, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7876885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7876885</a>]" pmid="7876885">Folkerth et al. (1995)</a> presented a complete autopsy study of a patient with ML IV whose mother was of Ashkenazi Jewish ancestry. They found that the storage material in neurons differed from that in nonneural cells, although inclusion material in all tissues was stained with periodic acid-Schiff, indicating accumulation of carbohydrates containing vicinal glycol structures. Neuronal inclusions stained with Sudan black, indicating accumulation of lipid, but not with Luxol-fast blue, suggesting that the stored lipid was not polar. In contrast, the storage material in hepatocytes, kidneys, and myocytes stained intensely with Luxol-fast blue, indicating the accumulation of polar lipids. Luxol-fast blue also failed to stain reticular endothelial cells. Because of this variation, <a href="#16" class="mim-tip-reference" title="Folkerth, R. D., Alroy, J., Lomakina, I., Skutelsky, E., Raghavan, S. S., Kolodny, E. H. <strong>Mucolipidosis IV: morphology and histochemistry of an autopsy case.</strong> J. Neuropath. Exp. Neurol. 54: 154-164, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7876885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7876885</a>]" pmid="7876885">Folkerth et al. (1995)</a> suggested that it was unlikely that mucolipidosis IV is due to a deficiency of a single enzyme such as a specific lysosomal hydrolase. They suggested instead that there may be a defect in intracellular packaging or transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7876885" 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="#30" class="mim-tip-reference" title="Schiffmann, R., Dwyer, N. K., Lubensky, I. A., Tsokos, M., Sutliff, V. E., Latimer, J. S., Frei, K. P., Brady, R. O., Barton, N. W., Blanchette-Mackie, E. J., Goldin, E. <strong>Constitutive achlorhydria in mucolipidosis type IV.</strong> Proc. Nat. Acad. Sci. 95: 1207-1212, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9448310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9448310</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9448310[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.95.3.1207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9448310">Schiffmann et al. (1998)</a> reported constitutive achlorhydria in ML IV. In a study of 15 ML IV patients, aged 2 to 23 years, over a period of 22 months, the authors found that some patients had iron deficiency, and that 14 patients had markedly elevated blood gastrin levels; the iron deficiency was thought to be secondary to decreased dietary iron absorption. None had vitamin B12 deficiency. Gastroscopy showed normal gross appearance in a 4- and 7-year-old patient, and mucosal atrophy in a 22-year-old patient. Parietal cells were present in normal numbers, but contained large cytoplasmic lysosomal inclusions. The parietal cells showed a selective lack of hydrochloric acid secretion that did not affect the ability to secrete intrinsic factor. Both subunits of the parietal cell H(+)/K(+)-ATPase were present, and both partially colocalized at the apical membrane. Other gastric epithelial cells appeared normal, but enterochromaffin-like cells were hyperplastic, indicating longstanding hypergastrinemia. <a href="#30" class="mim-tip-reference" title="Schiffmann, R., Dwyer, N. K., Lubensky, I. A., Tsokos, M., Sutliff, V. E., Latimer, J. S., Frei, K. P., Brady, R. O., Barton, N. W., Blanchette-Mackie, E. J., Goldin, E. <strong>Constitutive achlorhydria in mucolipidosis type IV.</strong> Proc. Nat. Acad. Sci. 95: 1207-1212, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9448310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9448310</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9448310[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.95.3.1207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9448310">Schiffmann et al. (1998)</a> suggested that the defective protein in ML IV is associated with the final stages of parietal cell activation and is critical for a specific type of cellular vacuolar trafficking between the cytoplasm and the apical membrane domain. The authors noted that the severity of the mucosal inflammation and atrophy found on stomach biopsies increased with age, secondary to longstanding achlorhydria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9448310" 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="#1" class="mim-tip-reference" title="Amir, N., Zlotogora, J., Bach, G. <strong>Mucolipidosis type IV: clinical spectrum and natural history.</strong> Pediatrics 79: 953-959, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2438637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2438637</a>]" pmid="2438637">Amir et al. (1987)</a> noted that the diagnosis of ML IV could be made by electron microscopic demonstration of storage organelles typical of the mucolipidoses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2438637" 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>Prenatal Diagnosis</em></strong></p><p>
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<a href="#9" class="mim-tip-reference" title="Caimi, L., Tettamanti, G., Berra, B., Sale, F. O., Borrone, C., Gatti, R., Durand, P., Martin, J. J. <strong>Mucolipidosis IV, a sialolipidosis due to ganglioside sialidase deficiency.</strong> J. Inherit. Metab. Dis. 5: 218-224, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6820444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6820444</a>] [<a href="https://doi.org/10.1007/BF02179146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6820444">Caimi et al. (1982)</a> noted that prenatal diagnosis of ML IV is possible with transmission electron microscopy of amniocytes, showing characteristic inclusions. <a href="#26" class="mim-tip-reference" title="Ornoy, A., Arnon, J., Grebner, E. E., Jackson, L. G., Bach, G. <strong>Early prenatal diagnosis of mucolipidosis IV. (Letter)</strong> Am. J. Med. Genet. 27: 983-985, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3425607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3425607</a>] [<a href="https://doi.org/10.1002/ajmg.1320270429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3425607">Ornoy et al. (1987)</a> proposed transmission electron microscopy with demonstration of lamellar bodies in endothelial cells of the chorionic villi for the prenatal diagnosis of ML IV. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3425607+6820444" 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="#6" class="mim-tip-reference" title="Bargal, R., Bach, G. <strong>Mucolipidosis type IV: abnormal transport of lipids to lysosomes.</strong> J. Inherit. Metab. Dis. 20: 625-632, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9323557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9323557</a>] [<a href="https://doi.org/10.1023/a:1005362123443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9323557">Bargal and Bach (1997)</a> found that phosphatidylcholine, as well as other phospholipids, sphingolipids, acid mucopolysaccharides, and gangliosides, accumulated in lysosomes of fibroblasts from patients with ML IV. Once the membrane macromolecules reached the lysosomes, they were normally catabolized and discharged. The findings suggested a defect in the endocytosis process of membranous components; there is excessive transportation of these macromolecules into lysosomes rather than their recycling to the plasma membrane. The authors noted that endocytosis of membrane components is different from receptor-mediated endocytosis, which is not affected in ML IV. The results explained the heterogeneity of the stored materials identified in ML IV. The normal catabolism of macromolecules in the lysosomes is reflected in the minor deterioration in the clinical manifestations of patients with this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9323557" 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 using various markers for endocytosis, <a href="#10" class="mim-tip-reference" title="Chen, C.-S., Bach, G., Pagano, R. E. <strong>Abnormal transport along the lysosomal pathway in mucolipidosis, type IV disease.</strong> Proc. Nat. Acad. Sci. 95: 6373-6378, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9600972[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.95.11.6373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600972">Chen et al. (1998)</a> found that plasma membrane internalization and recycling were nearly identical in ML IV and normal fibroblasts. A fluorescent analog of lactosylceramide (LacCer), a marker of plasma membrane lipid internalization and transport, demonstrated accumulation of fluorescent LacCer in the lysosomes more rapidly and to a greater extent in ML IV cells than in normal fibroblasts. By 60 minutes, LacCer apparently decreased in the lysosomes of normal fibroblasts but not in ML IV cells, suggesting that lipid efflux from the lysosomes was also impaired. The findings suggested a defect in transport along the lysosomal pathway, affecting membrane sorting and/or late steps of endocytosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Goldin, E., Blanchette-Mackie, E. J., Dwyer, N. K., Pentchev, P. G., Brady, R. O. <strong>Cultured skin fibroblasts derived from patients with mucolipidosis 4 are auto-fluorescent.</strong> Pediat. Res. 37: 687-692, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7651750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7651750</a>] [<a href="https://doi.org/10.1203/00006450-199506000-00003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7651750">Goldin et al. (1995)</a> found that skin fibroblasts derived from ML IV patients were autofluorescent, which was presumably related to the specific lysosomal storage material. <a href="#19" class="mim-tip-reference" title="Goldin, E., Cooney, A., Kaneski, C. R., Brady, R. O., Schiffmann, R. <strong>Mucolipidosis IV consists of one complementation group.</strong> Proc. Nat. Acad. Sci. 96: 8562-8566, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10411915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10411915</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10411915[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.96.15.8562" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10411915">Goldin et al. (1999)</a> studied cells from more than 20 ML IV patients, most of them of Ashkenazi Jewish ancestry, who were involved in a longitudinal study conducted at the Clinical Center of the National Institutes of Health. Patients of other ethnic groups included 3 non-Jewish Caucasians and 1 South American Indian. Complementation studies showed that all patients with ML IV, regardless of ancestry or disease severity, have a mutation in the same gene, excluding genetic heterogeneity. In addition <a href="#19" class="mim-tip-reference" title="Goldin, E., Cooney, A., Kaneski, C. R., Brady, R. O., Schiffmann, R. <strong>Mucolipidosis IV consists of one complementation group.</strong> Proc. Nat. Acad. Sci. 96: 8562-8566, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10411915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10411915</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10411915[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.96.15.8562" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10411915">Goldin et al. (1999)</a> found high sensitivity to chloroquine in cultured ML IV fibroblasts, which was discovered when different lysosomotropic agents were screened for their ability to kill selectively ML IV fibroblasts in culture. Antimalarial agents with properties similar to chloroquine, such as primaquine or quinacrine, exhibited effects similar to chloroquine, whereas other antimalarial drugs of different chemical structure, such as artemisinin, did not kill fibroblasts even at very high concentrations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7651750+10411915" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In fibroblasts from patients with ML IV, <a href="#34" class="mim-tip-reference" title="Vergarajauregui, S., Connelly, P. S., Daniels, M. P., Puertollano, R. <strong>Autophagic dysfunction in mucolipidosis type IV patients.</strong> Hum. Molec. Genet. 17: 2723-2737, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18550655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18550655</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18550655[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/10.1093/hmg/ddn174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18550655">Vergarajauregui et al. (2008)</a> observed increased basal levels of autophagy, as evidenced by increased LC3 (MAP1LC3A; <a href="/entry/601242">601242</a>) in discrete vesicular structures compared to wildtype fibroblasts. The structures were consistent with autophagosomes, and most of these autophagosomes contained ubiquitinated protein aggregates. Although fusion of autophagosomes with late endosomal lysosomal pathway could occur in ML IV fibroblasts under starvation stress, the process was delayed compared to wildtype fibroblasts. Monitoring of the PDGFR (<a href="/entry/173410">173410</a>) in MCOLN1-deficient cells showed significantly impaired degradation, indicating that MCOLN1 is required for efficient transport and delivery of material from late endosomes and autophagosomes to lysosomes. <a href="#34" class="mim-tip-reference" title="Vergarajauregui, S., Connelly, P. S., Daniels, M. P., Puertollano, R. <strong>Autophagic dysfunction in mucolipidosis type IV patients.</strong> Hum. Molec. Genet. 17: 2723-2737, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18550655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18550655</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18550655[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/10.1093/hmg/ddn174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18550655">Vergarajauregui et al. (2008)</a> suggested that the findings were consistent with a disease model in which abnormal accumulation of ubiquitinated proteins may contribute to neurodegeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18550655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By linkage analysis, <a href="#31" class="mim-tip-reference" title="Slaugenhaupt, S. A., Acierno, J. S., Jr., Helbling, L. A., Bove, C., Goldin, E., Bach, G., Schiffmann, R., Gusella, J. F. <strong>Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes.</strong> Am. J. Hum. Genet. 65: 773-778, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441585</a>] [<a href="https://doi.org/10.1086/302549" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441585">Slaugenhaupt et al. (1999)</a> mapped the ML IV locus to chromosome 19p13.3-p13.2 in 13 families. A maximum lod score of 5.51 with no recombination was observed at marker D19S873. Several markers in the linked interval also displayed significant linkage disequilibrium with the disorder. <a href="#31" class="mim-tip-reference" title="Slaugenhaupt, S. A., Acierno, J. S., Jr., Helbling, L. A., Bove, C., Goldin, E., Bach, G., Schiffmann, R., Gusella, J. F. <strong>Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes.</strong> Am. J. Hum. Genet. 65: 773-778, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441585</a>] [<a href="https://doi.org/10.1086/302549" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441585">Slaugenhaupt et al. (1999)</a> constructed haplotypes in 26 Ashkenazi Jewish families and demonstrated the existence of 2 founder chromosomes in this population: a major and minor haplotype was observed for 39 (75%) and 11 (21%), respectively, of the 52 chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441585" 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 ML4 in the patients reported by <a href="#5" class="mim-tip-reference" title="Bargal, R., Avidan, N., Ben-Asher, E., Olender, Z., Zeigler, M., Frumkin, A., Raas-Rothschild, A., Glusman, G., Lancet, D., Bach, G. <strong>Identification of the gene causing mucolipidosis type IV.</strong> Nature Genet. 26: 118-121, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973263</a>] [<a href="https://doi.org/10.1038/79095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973263">Bargal et al. (2000)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973263" 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 21 Ashkenazi Jewish ML IV patients, <a href="#5" class="mim-tip-reference" title="Bargal, R., Avidan, N., Ben-Asher, E., Olender, Z., Zeigler, M., Frumkin, A., Raas-Rothschild, A., Glusman, G., Lancet, D., Bach, G. <strong>Identification of the gene causing mucolipidosis type IV.</strong> Nature Genet. 26: 118-121, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973263</a>] [<a href="https://doi.org/10.1038/79095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973263">Bargal et al. (2000)</a> identified 2 mutations in the MCOLN1 gene (<a href="/entry/605248#0001">605248.0001</a>; <a href="/entry/605248#0002">605248.0002</a>) in correlation with the major and minor haplotypes identified by <a href="#31" class="mim-tip-reference" title="Slaugenhaupt, S. A., Acierno, J. S., Jr., Helbling, L. A., Bove, C., Goldin, E., Bach, G., Schiffmann, R., Gusella, J. F. <strong>Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes.</strong> Am. J. Hum. Genet. 65: 773-778, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441585</a>] [<a href="https://doi.org/10.1086/302549" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441585">Slaugenhaupt et al. (1999)</a>. Six patients were compound heterozygous for both mutations and 2 patients were compound heterozygous for 1 of the founder mutations and a second unidentified mutation. The clinical manifestations of all the patients showed similar severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10441585+10973263" 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="#32" class="mim-tip-reference" title="Sun, M., Goldin, E., Stahl, S., Falardeau, J. L., Kennedy, J. C., Acierno, J. S., Jr., Bove, C., Kaneski, C. R., Nagle, J., Bromley, M.C., Colman, M., Schiffmann, R., Slaugenhaupt, S. A. <strong>Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.</strong> Hum. Molec. Genet. 9: 2471-2478, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030752</a>] [<a href="https://doi.org/10.1093/hmg/9.17.2471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11030752">Sun et al. (2000)</a> identified mutations in the MCOLN1 gene (<a href="/entry/605248#0004">605248.0004</a>-<a href="/entry/605248#0006">605248.0006</a>) in patients with ML IV. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11030752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 4-year-old girl with ML IV, <a href="#20" class="mim-tip-reference" title="Goldin, E., Stahl, S., Cooney, A. M., Kaneski, C. R., Gupta, S., Brady, R. O., Ellis, J. R., Schiffmann, R. <strong>Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV.</strong> Hum. Mutat. 24: 460-465, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523648</a>] [<a href="https://doi.org/10.1002/humu.20094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15523648">Goldin et al. (2004)</a> identified compound heterozygous mutations in the MCOLN1 gene (<a href="/entry/605248#0007">605248.0007</a>-<a href="/entry/605248#0008">605248.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15523648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a girl with an unusually mild case of ML IV, who was not of Ashkenazi Jewish origin, <a href="#14" class="mim-tip-reference" title="Dobrovolny, R., Liskova, P., Ledvinova, J., Poupetova, H., Asfaw, B., Filipec, M., Jirsova, K., Kraus, J., Elleder, M. <strong>Mucolipidosis IV: report of a case with ocular restricted phenotype caused by leaky splice mutation.</strong> Am. J. Ophthal. 143: 663-671, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17239335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17239335</a>] [<a href="https://doi.org/10.1016/j.ajo.2006.11.049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17239335">Dobrovolny et al. (2007)</a> identified compound heterozygous mutations in the MCOLN1 gene (<a href="/entry/605248#0005">605248.0005</a>; <a href="/entry/605248#0009">605248.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17239335" 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="#29" class="mim-tip-reference" title="Riedel, K. G., Zwaan, J., Kenyon, K. R., Kolodny, E. H., Hanninen, L., Albert, D. M. <strong>Ocular abnormalities in mucolipidosis IV.</strong> Am. J. Ophthal. 99: 125-136, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3918453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3918453</a>] [<a href="https://doi.org/10.1016/0002-9394(85)90220-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3918453">Riedel et al. (1985)</a> stated that 17 cases of ML IV had been reported; about half of them had Ashkenazi Jewish ancestry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3918453" 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="Chen, C.-S., Bach, G., Pagano, R. E. <strong>Abnormal transport along the lysosomal pathway in mucolipidosis, type IV disease.</strong> Proc. Nat. Acad. Sci. 95: 6373-6378, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9600972[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.95.11.6373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600972">Chen et al. (1998)</a> stated that over 80% of the patients in whom the diagnosis of ML IV had been made were Ashkenazi Jews, including severely affected and mildly affected patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600972" 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="#28" class="mim-tip-reference" title="Raas-Rothschild, A., Bargal, R., DellaPergola, S., Zeigler, M., Bach, G. <strong>Mucolipidosis type IV: the origin of the disease in the Ashkenazi Jewish population.</strong> Europ. J. Hum. Genet. 7: 496-498, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352940</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10352940">Raas-Rothschild et al. (1999)</a> interviewed 17 Israeli Ashkenazi families with ML IV patients to study their family origin. Although the families immigrated to Israel from various European countries, they could all trace their roots 3 to 4 generations back to northern Poland or the immediate neighboring country, Lithuania. Furthermore, there are only 1 or 2 ultraorthodox families among the 70 to 80 Ashkenazi families with ML IV patients worldwide, a marked underrepresentation of this group, which constitutes at least 10% of the Ashkenazi population. These data indicated that the ML IV mutation occurred only around the 18th or 19th century after the major expansion of this population, in a founder in this defined European region belonging to a modern, secular family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#21" class="mim-tip-reference" title="Goutieres, F., Arsenio-Nunes, M.-L., Aicardi, J. <strong>Mucolipidosis IV.</strong> Neuropadiatrie 10: 321-330, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/231746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">231746</a>] [<a href="https://doi.org/10.1055/s-0028-1085335" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="231746">Goutieres et al. (1979)</a> suggested that the defect in ML IV may concern ganglioside sialidase (neuraminidase), 95% of which is located in the plasma membrane, the rest in lysosomes. They noted that glycoprotein sialidase was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=231746" 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="#7" class="mim-tip-reference" title="Ben-Yoseph, Y., Momoi, T., Hahn, L. C., Nadler, H. L. <strong>Catalytically defective ganglioside neuraminidase in mucolipidosis IV.</strong> Clin. Genet. 21: 374-381, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6813002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6813002</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1982.tb01390.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6813002">Ben-Yoseph et al. (1982)</a> found deficiency of neuraminidase activity toward GD(1a) and GD(1b) gangliosides; parents showed intermediate levels of enzyme activity. Residual enzyme had a K(m) about 18 times higher than that of the normal enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6813002" 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>Unlike other lysosomal storage diseases, ML IV is not associated with a lack of lysosomal hydrolases; instead, ML IV cells display abnormal endocytosis of lipids and accumulate large vesicles, indicating that a defect in endocytosis may underlie the disease. <a href="#15" class="mim-tip-reference" title="Fares, H., Greenwald, I. <strong>Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog.</strong> Nature Genet. 28: 64-68, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11326278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11326278</a>] [<a href="https://doi.org/10.1038/ng0501-64" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11326278">Fares and Greenwald (2001)</a> reported the identification of a loss-of-function mutation in the Caenorhabditis elegans mucolipin-1 homolog, cup5, and showed that this mutation results in an enhanced rate of uptake of fluid-phase markers, decreased degradation of endocytosed protein, and accumulation of large vacuoles. Overexpression of cup5+ causes the opposite phenotype, indicating that cup5 activity controls aspects of endocytosis. The authors concluded that the C. elegans cup5 mutant may be a useful model for studying conserved aspects of mucolipin-1 structure and function and for assessing the effects of potential therapeutic compounds. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11326278" 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="#Bach1977" class="mim-tip-reference" title="Bach, G., Ziegler, M., Kohn, G., Cohen, M. M. <strong>Mucopolysaccharidosis accumulation in cultured skin fibroblasts derived from patients with mucolipidosis IV.</strong> Am. J. Hum. Genet. 29: 610-618, 1977.">Bach et al. (1977)</a>; <a href="#Bach1979" class="mim-tip-reference" title="Bach, G. <strong>Mucolipidosis type IV. In: Goodman, R. E.; Motulsky, A. G. (eds.): Genetic Diseases Among Ashkenazi Jews.</strong> New York: Raven Press (pub.) 1979. Pp. 187-200.">Bach et al. (1979)</a>; <a href="#Bach1979" class="mim-tip-reference" title="Bach, G. <strong>Mucolipidosis type IV. In: Goodman, R. E.; Motulsky, A. G. (eds.): Genetic Diseases Among Ashkenazi Jews.</strong> New York: Raven Press (pub.) 1979. Pp. 187-200.">Bach (1979)</a>; <a href="#Dangel1985" class="mim-tip-reference" title="Dangel, M. E., Bremer, D. L., Rogers, G. L. <strong>Treatment of corneal opacification in mucolipidosis IV with conjunctival transplantation.</strong> Am. J. Ophthal. 99: 137-141, 1985.">Dangel et al.
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(1985)</a>; <a href="#Kohn1977" class="mim-tip-reference" title="Kohn, G., Livni, N., Ornoy, A., Sekeles, E., Beyth, Y., Legum, C., Bach, G., Cohen, M. M. <strong>Prenatal diagnosis of mucolipidosis IV by electron microscopy.</strong> J. Pediat. 90: 62-66, 1977.">Kohn et al. (1977)</a>; <a href="#Lake1982" class="mim-tip-reference" title="Lake, B. D., Milla, P. J., Taylor, D. S. I., Young, E. P. <strong>A mild variant of mucolipidosis type 4 (ML4).</strong> Birth Defects Orig. Art. Ser. 18(6): 391-404, 1982.">Lake et al. (1982)</a>; <a href="#Newell1975" class="mim-tip-reference" title="Newell, F. W., Matalon, R., Mayer, S. <strong>A new mucolipidosis with psychomotor retardation, corneal clouding, and retinal degeneration.</strong> Am. J. Ophthal. 80: 440-449, 1975.">Newell et al. (1975)</a>; <a href="#Zeigler1981" class="mim-tip-reference" title="Zeigler, M., Bach, G. <strong>The nature of the sialidase deficiency in mucolipidosis type IV. (Abstract)</strong> Sixth International Congress of Human Genetics, Jerusalem 1981. P. 78.">Zeigler and Bach (1981)</a>; <a href="#Zwaan1982" class="mim-tip-reference" title="Zwaan, J., Kenyon, K. R. <strong>Two brothers with presumed mucolipidosis IV.</strong> Birth Defects Orig. Art. Ser. 18(6): 381-390, 1982.">Zwaan and Kenyon (1982)</a>
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Amir, N., Zlotogora, J., Bach, G.
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<strong>Mucolipidosis type IV: clinical spectrum and natural history.</strong>
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Pediatrics 79: 953-959, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2438637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2438637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2438637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Bach, G., Ziegler, M., Kohn, G., Cohen, M. M.
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<strong>Mucopolysaccharidosis accumulation in cultured skin fibroblasts derived from patients with mucolipidosis IV.</strong>
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Am. J. Hum. Genet. 29: 610-618, 1977.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/145180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">145180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=145180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Mucolipidosis type IV: ganglioside sialidase deficiency.</strong>
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Biochem. Biophys. Res. Commun. 90: 1341-1347, 1979.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/518603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">518603</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=518603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0006-291x(79)91183-5" target="_blank">Full Text</a>]
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<strong>Mucolipidosis type IV. In: Goodman, R. E.; Motulsky, A. G. (eds.): Genetic Diseases Among Ashkenazi Jews.</strong>
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New York: Raven Press (pub.) 1979. Pp. 187-200.
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Bargal, R., Avidan, N., Ben-Asher, E., Olender, Z., Zeigler, M., Frumkin, A., Raas-Rothschild, A., Glusman, G., Lancet, D., Bach, G.
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<strong>Identification of the gene causing mucolipidosis type IV.</strong>
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Nature Genet. 26: 118-121, 2000.
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[<a href="https://doi.org/10.1038/79095" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1023/a:1005362123443" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1982.tb01390.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(74)80671-2" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF02179146" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.95.11.6373" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320410310" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320120308" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0002-9394(85)90221-1" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ajo.2006.11.049" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.96.15.8562" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/830895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">830895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=830895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(77)80765-8" target="_blank">Full Text</a>]
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<a id="Lake1982" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lake, B. D., Milla, P. J., Taylor, D. S. I., Young, E. P.
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<strong>A mild variant of mucolipidosis type 4 (ML4).</strong>
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Birth Defects Orig. Art. Ser. 18(6): 391-404, 1982.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7171767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7171767</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7171767" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Merin1975" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Merin, S., Livni, N., Berman, E. R., Yatziv, S.
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<strong>Mucolipidosis IV: ocular, systemic, and ultrastructural findings.</strong>
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Invest. Ophthal. 14: 437-448, 1975.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/166049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">166049</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=166049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Newell1975" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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<strong>A new mucolipidosis with psychomotor retardation, corneal clouding, and retinal degeneration.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/169696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">169696</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=169696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0002-9394(75)90532-2" target="_blank">Full Text</a>]
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<a id="Ornoy1987" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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<strong>Early prenatal diagnosis of mucolipidosis IV. (Letter)</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3425607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3425607</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3425607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320270429" target="_blank">Full Text</a>]
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<a id="Pradhan2002" class="mim-anchor"></a>
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Pradhan, S. M., Atchaneeyasakul, L.-O., Appukuttan, B., Mixon, R. N., McFarland, T. J., Billingslea, A. M., Wilson, D. J., Stout, J. T., Weleber, R. G.
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<strong>Electronegative electroretinogram in mucolipidosis IV.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11786056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11786056</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11786056" 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/10.1001/archopht.120.1.45" target="_blank">Full Text</a>]
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<a id="Raas-Rothschild1999" class="mim-anchor"></a>
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Raas-Rothschild, A., Bargal, R., DellaPergola, S., Zeigler, M., Bach, G.
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<strong>Mucolipidosis type IV: the origin of the disease in the Ashkenazi Jewish population.</strong>
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Europ. J. Hum. Genet. 7: 496-498, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352940" 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/10.1038/sj.ejhg.5200277" target="_blank">Full Text</a>]
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<a id="Riedel1985" class="mim-anchor"></a>
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Riedel, K. G., Zwaan, J., Kenyon, K. R., Kolodny, E. H., Hanninen, L., Albert, D. M.
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<strong>Ocular abnormalities in mucolipidosis IV.</strong>
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Am. J. Ophthal. 99: 125-136, 1985.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3918453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3918453</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3918453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0002-9394(85)90220-x" target="_blank">Full Text</a>]
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<a id="Schiffmann1998" class="mim-anchor"></a>
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Schiffmann, R., Dwyer, N. K., Lubensky, I. A., Tsokos, M., Sutliff, V. E., Latimer, J. S., Frei, K. P., Brady, R. O., Barton, N. W., Blanchette-Mackie, E. J., Goldin, E.
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<strong>Constitutive achlorhydria in mucolipidosis type IV.</strong>
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Proc. Nat. Acad. Sci. 95: 1207-1212, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9448310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9448310</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9448310[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=9448310" 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.95.3.1207" target="_blank">Full Text</a>]
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Slaugenhaupt, S. A., Acierno, J. S., Jr., Helbling, L. A., Bove, C., Goldin, E., Bach, G., Schiffmann, R., Gusella, J. F.
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<strong>Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes.</strong>
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Am. J. Hum. Genet. 65: 773-778, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441585</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441585" 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/10.1086/302549" target="_blank">Full Text</a>]
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<a id="Sun2000" class="mim-anchor"></a>
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Sun, M., Goldin, E., Stahl, S., Falardeau, J. L., Kennedy, J. C., Acierno, J. S., Jr., Bove, C., Kaneski, C. R., Nagle, J., Bromley, M.C., Colman, M., Schiffmann, R., Slaugenhaupt, S. A.
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<strong>Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.</strong>
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Hum. Molec. Genet. 9: 2471-2478, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030752</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11030752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/9.17.2471" target="_blank">Full Text</a>]
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<a id="Tellez-Nagel1976" class="mim-anchor"></a>
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Tellez-Nagel, I., Rapin, I., Iwamoto, T., Johnson, A. B., Norton, W. T., Nitowsky, H.
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<strong>Mucolipidosis IV: clinical, ultrastructural, histochemical, and chemical studies of a case, including a brain biopsy.</strong>
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Arch. Neurol. 33: 828-835, 1976.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/187156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">187156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=187156" 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/10.1001/archneur.1976.00500120032005" target="_blank">Full Text</a>]
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Vergarajauregui, S., Connelly, P. S., Daniels, M. P., Puertollano, R.
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<strong>Autophagic dysfunction in mucolipidosis type IV patients.</strong>
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Hum. Molec. Genet. 17: 2723-2737, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18550655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18550655</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18550655[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=18550655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddn174" target="_blank">Full Text</a>]
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Zeigler, M., Bach, G.
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<strong>The nature of the sialidase deficiency in mucolipidosis type IV. (Abstract)</strong>
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Sixth International Congress of Human Genetics, Jerusalem 1981. P. 78.
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Zwaan, J., Kenyon, K. R.
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<strong>Two brothers with presumed mucolipidosis IV.</strong>
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Birth Defects Orig. Art. Ser. 18(6): 381-390, 1982.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7171766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7171766</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7171766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 7/29/2010
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 11/2/2007<br>Cassandra L. Kniffin - reorganized : 12/2/2004<br>Jane Kelly - updated : 6/21/2002<br>George E. Tiller - updated : 12/6/2000<br>Victor A. McKusick - updated : 8/30/2000<br>Victor A. McKusick - updated : 9/20/1999<br>Victor A. McKusick - updated : 8/13/1999<br>Ada Hamosh - updated : 7/15/1999<br>Victor A. McKusick - updated : 6/12/1998<br>Victor A. McKusick - updated : 3/13/1998<br>Victor A. McKusick - updated : 2/19/1998<br>Orest Hurko - updated : 8/2/1995
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Victor A. McKusick : 6/4/1986
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carol : 05/09/2024
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carol : 08/09/2016<br>carol : 07/13/2015<br>wwang : 8/6/2010<br>ckniffin : 7/29/2010<br>ckniffin : 5/25/2010<br>joanna : 12/24/2007<br>carol : 11/26/2007<br>carol : 11/2/2007<br>ckniffin : 11/2/2007<br>wwang : 11/13/2006<br>terry : 11/10/2006<br>carol : 4/5/2005<br>alopez : 2/10/2005<br>wwang : 1/25/2005<br>carol : 12/2/2004<br>ckniffin : 11/22/2004<br>carol : 5/30/2003<br>carol : 6/24/2002<br>terry : 6/21/2002<br>mcapotos : 7/6/2001<br>carol : 7/6/2001<br>carol : 12/6/2000<br>joanna : 9/11/2000<br>alopez : 8/31/2000<br>alopez : 8/31/2000<br>alopez : 8/31/2000<br>terry : 8/30/2000<br>terry : 8/30/2000<br>alopez : 12/6/1999<br>jlewis : 9/30/1999<br>terry : 9/20/1999<br>carol : 8/17/1999<br>carol : 8/17/1999<br>terry : 8/13/1999<br>alopez : 7/26/1999<br>terry : 7/15/1999<br>alopez : 6/16/1998<br>terry : 6/12/1998<br>joanna : 5/8/1998<br>psherman : 3/13/1998<br>terry : 3/6/1998<br>mark : 2/26/1998<br>terry : 2/19/1998<br>mimman : 2/8/1996<br>mark : 8/2/1995<br>mimadm : 5/17/1994<br>terry : 5/7/1994<br>warfield : 4/15/1994<br>supermim : 3/17/1992<br>carol : 3/4/1992
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<span class="mim-font">
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<strong>#</strong> 252650
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<h3>
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MUCOLIPIDOSIS IV; ML4
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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ML IV<br />
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SIALOLIPIDOSIS
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<strong>SNOMEDCT:</strong> 725296006;
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<strong>ICD10CM:</strong> E75.11;
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<strong>ORPHA:</strong> 578;
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<strong>DO:</strong> 0080490;
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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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19p13.2
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Mucolipidosis IV
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<span class="mim-font">
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252650
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Autosomal recessive
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<span class="mim-font">
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3
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MCOLN1
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<span class="mim-font">
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605248
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because mucolipidosis IV (ML4) is caused by homozygous or compound heterozygous mutation in the MCOLN1 gene (605248) on chromosome 19p13.</p>
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<strong>Description</strong>
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<p>Mucolipidosis IV (ML4) is an autosomal recessive neurodegenerative lysosomal storage disorder characterized by psychomotor retardation and ophthalmologic abnormalities. The lysosomal hydrolases in ML IV are normal, in contrast to most other storage diseases. The disorder results from a defect in transport along the lysosomal pathway, affecting membrane sorting and/or late steps of endocytosis, which causes intracellular accumulation of lysosomal substrates. Over 80% of the patients in whom the diagnosis of ML IV has been made are Ashkenazi Jews, including severely affected and mildly affected patients (summary by Chen et al., 1998). </p>
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<strong>Clinical Features</strong>
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<p>Berman et al. (1974) reported an Ashkenazi Jewish infant with congenital corneal clouding and abnormal systemic storage bodies. Lysosomal hydrolases were normal. The disorder was characterized as a new variant of mucolipidosis because electron microscopy showed lysosomal storage of lipids together with water-soluble granulated substances. </p><p>Merin et al. (1975) described a disorder, termed mucolipidosis IV, in 4 unrelated children of Ashkenazi extraction traced to southern Poland. There were 3 females and 1 male. The most prominent clinical feature was corneal clouding from birth or early infancy, which was the presenting symptom in 2, followed by psychomotor retardation apparent by the end of the first year of life. Skeletal dysplasia, facial dysmorphism, and hepatosplenomegaly were absent. Conjunctival biopsies showed 2 types of abnormal fibroblast inclusion bodies: single-membrane-limited cytoplasmic vacuoles containing both fibrillogranular material and membranous lamellae, and lamellar and concentric bodies resembling those of Tay-Sachs disease (272800). Electroretinogram (ERG) performed in 1 patient was subnormal. The disorder was characterized as a mucolipidosis because electron microscopy showed lysosomal storage of lipids together with water-soluble granulated substances. </p><p>Tellez-Nagel et al. (1976) reported a 7-year-old Ashkenazi Jewish boy who showed developmental regression at age 8 months. Corneal, conjunctival, and cerebral biopsies showed lipid-like and mucopolysaccharide-like concentric membranous lamellar lysosomal inclusions which were reminiscent of those found in the gangliosidoses. In the brain, dense fluorescent inclusions resembled those in ceroid-lipofuscinosis (see, e.g., 256730). Total ganglioside content of the white matter was increased, but the pattern was normal. The findings were consistent with ML IV. Goutieres et al. (1979) described 5 cases of mucolipidosis IV in non-Jews. Four patients were in 2 sibships. </p><p>Crandall et al. (1982) reported a 2-year-old Ashkenazi Jewish girl who presented with developmental delay and microcephaly. Photophobia and corneal haze were noted at 9 months of age, and fibrous dysplasia and corneal opacities were found at 18 months. At 2 years, she had esotropia, mild coarse facies, and hypotonia, and was unable to walk or speak. Examination at 5 years showed neurologic progression of the disorder, with hoarse cry, nystagmus, truncal titubation, spasticity, dystonic posturing, hyperreflexia, and extensor plantar responses. She was unable to sit without support and did not respond to visual stimuli. There was no organomegaly, and urine analysis showed no oligosaccharide or mucopolysaccharide excretion. Electron microscopy showed cytoplasmic granular inclusions and concentric lamellar structures in liver, muscle, and nerve. Phospholipids were increased in liver, skin fibroblasts, and urine. </p><p>Caimi et al. (1982) reported a 22-year-old Italian woman with cloudy corneae, capsular lens opacities, and severe and progressive mental and motor deterioration. Ultrastructural skin biopsy showed membranous cytoplasmic bodies in Schwann cells, vessel walls, fibroblasts, smooth muscle fibers, and sweat glands. There was a complete deficiency of ganglioside sialidase. Urine analysis showed accumulation of all phospholipid species, of several glycolipids, and of gangliosides. Caimi et al. (1982) suggested that ML IV could be called sialolipidosis to distinguish it from sialidosis (256550), in which the sialidase (neuraminidase) for glycoprotein and water-soluble oligosaccharides is deficient. They noted that ML IV heterozygotes show partial deficiency of ganglioside sialidase. </p><p>Amir et al. (1987) reported heterogeneity in ophthalmologic features in 20 ML IV patients who ranged in age from 2 to 17 years, noting differences in age at onset and in degree and clinical course of corneal opacities and retinal involvement. One patient, aged 5, had no corneal opacity although her vision was greatly reduced because of severe myopia and retinal degeneration. On the other hand, corneal opacities were congenital in 11 of the 20 cases. All patients had psychomotor retardation and visual impairment during the first year of life. The maximal developmental level achieved was 12 to 15 months. </p><p>Chitayat et al. (1991) reported 5 patients with ML IV from 3 Ashkenazi Jewish families. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus. None progressed beyond the developmental age of 15 months. In 1 patient, death was due to aspiration at age 17 years; the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and was 32 years old at the time of report. </p><p>Bargal and Bach (1997) observed that even more severely affected ML IV patients, despite an early age at onset, showed very slow or hardly any deterioration in the clinical picture for the first 2 to 3 decades of life. </p><p>In 14 of 15 ML IV patients, Frei et al. (1998) found a hypoplastic corpus callosum with absent rostrum and a dysplastic or absent splenium, dysmyelinating white matter abnormalities, and increased ferritin deposits in the thalamus and basal ganglia. Atrophy of the cerebellum and cerebrum was observed in older patients, reflecting disease progression. </p><p>Pradhan et al. (2002) presented the progression of ERG findings in 2 patients with mucolipidosis IV. Both patients showed greater loss of b-wave than a-wave responses. In both, rod-mediated responses were minimal, cone-mediated responses were severely subnormal, and cone b-wave implicit times were prolonged. The electronegative ERG configuration suggested that the primary retinal disturbance in mucolipidosis IV might occur at or proximal to the photoreceptor terminals. </p><p>Goldin et al. (2004) reported a 4-year-old Canadian girl of English and Scottish ancestry with ML IV. She exhibited developmental delay, hypotonia, ataxia, central corneal clouding, and mild photophobia as a relatively moderate phenotype. No organomegaly was present. She walked only with a walker. She was without speech but used about 20 signs to communicate with her parents. She also was able to feed herself with her fingers. Skin biopsy showed membrane-bound osmiophilic lysosomal inclusions. She was compound heterozygous for 2 mutations in the MCOLN1 gene only 1 of which, inherited from the father, was expressed (see 605248.0007). </p><p>Dobrovolny et al. (2007) reported an usually mild case of ML IV. The patient was a girl, not of Ashkenazi Jewish origin, who developed corneal cloudiness at age 2 years. She later developed progressive decreased visual acuity, corneal abrasions, and strabismus. At age 12 years, she showed retinal pigment abnormalities in the macula and retinal vessel attenuation. VEP and ERP examinations were consistent with bilateral retinal dystrophy. Ultrastructural examination showed storage lysosomes filled with either concentric membranes or lucent precipitate in corneal and conjunctival epithelia and vascular endothelium. There was also evidence of gastric parietal cell involvement leading to a compensatory increase in gastrin production. Otherwise, the patient had normal psychomotor development and no neurologic abnormalities. </p>
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<h4>
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<strong>Biochemical Features</strong>
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</h4>
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<p>Folkerth et al. (1995) presented a complete autopsy study of a patient with ML IV whose mother was of Ashkenazi Jewish ancestry. They found that the storage material in neurons differed from that in nonneural cells, although inclusion material in all tissues was stained with periodic acid-Schiff, indicating accumulation of carbohydrates containing vicinal glycol structures. Neuronal inclusions stained with Sudan black, indicating accumulation of lipid, but not with Luxol-fast blue, suggesting that the stored lipid was not polar. In contrast, the storage material in hepatocytes, kidneys, and myocytes stained intensely with Luxol-fast blue, indicating the accumulation of polar lipids. Luxol-fast blue also failed to stain reticular endothelial cells. Because of this variation, Folkerth et al. (1995) suggested that it was unlikely that mucolipidosis IV is due to a deficiency of a single enzyme such as a specific lysosomal hydrolase. They suggested instead that there may be a defect in intracellular packaging or transport. </p>
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<strong>Other Features</strong>
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<p>Schiffmann et al. (1998) reported constitutive achlorhydria in ML IV. In a study of 15 ML IV patients, aged 2 to 23 years, over a period of 22 months, the authors found that some patients had iron deficiency, and that 14 patients had markedly elevated blood gastrin levels; the iron deficiency was thought to be secondary to decreased dietary iron absorption. None had vitamin B12 deficiency. Gastroscopy showed normal gross appearance in a 4- and 7-year-old patient, and mucosal atrophy in a 22-year-old patient. Parietal cells were present in normal numbers, but contained large cytoplasmic lysosomal inclusions. The parietal cells showed a selective lack of hydrochloric acid secretion that did not affect the ability to secrete intrinsic factor. Both subunits of the parietal cell H(+)/K(+)-ATPase were present, and both partially colocalized at the apical membrane. Other gastric epithelial cells appeared normal, but enterochromaffin-like cells were hyperplastic, indicating longstanding hypergastrinemia. Schiffmann et al. (1998) suggested that the defective protein in ML IV is associated with the final stages of parietal cell activation and is critical for a specific type of cellular vacuolar trafficking between the cytoplasm and the apical membrane domain. The authors noted that the severity of the mucosal inflammation and atrophy found on stomach biopsies increased with age, secondary to longstanding achlorhydria. </p>
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<strong>Diagnosis</strong>
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<span class="mim-text-font">
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<p>Amir et al. (1987) noted that the diagnosis of ML IV could be made by electron microscopic demonstration of storage organelles typical of the mucolipidoses. </p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
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Caimi et al. (1982) noted that prenatal diagnosis of ML IV is possible with transmission electron microscopy of amniocytes, showing characteristic inclusions. Ornoy et al. (1987) proposed transmission electron microscopy with demonstration of lamellar bodies in endothelial cells of the chorionic villi for the prenatal diagnosis of ML IV. </p>
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<strong>Pathogenesis</strong>
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<p>Bargal and Bach (1997) found that phosphatidylcholine, as well as other phospholipids, sphingolipids, acid mucopolysaccharides, and gangliosides, accumulated in lysosomes of fibroblasts from patients with ML IV. Once the membrane macromolecules reached the lysosomes, they were normally catabolized and discharged. The findings suggested a defect in the endocytosis process of membranous components; there is excessive transportation of these macromolecules into lysosomes rather than their recycling to the plasma membrane. The authors noted that endocytosis of membrane components is different from receptor-mediated endocytosis, which is not affected in ML IV. The results explained the heterogeneity of the stored materials identified in ML IV. The normal catabolism of macromolecules in the lysosomes is reflected in the minor deterioration in the clinical manifestations of patients with this disorder. </p><p>By using various markers for endocytosis, Chen et al. (1998) found that plasma membrane internalization and recycling were nearly identical in ML IV and normal fibroblasts. A fluorescent analog of lactosylceramide (LacCer), a marker of plasma membrane lipid internalization and transport, demonstrated accumulation of fluorescent LacCer in the lysosomes more rapidly and to a greater extent in ML IV cells than in normal fibroblasts. By 60 minutes, LacCer apparently decreased in the lysosomes of normal fibroblasts but not in ML IV cells, suggesting that lipid efflux from the lysosomes was also impaired. The findings suggested a defect in transport along the lysosomal pathway, affecting membrane sorting and/or late steps of endocytosis. </p><p>Goldin et al. (1995) found that skin fibroblasts derived from ML IV patients were autofluorescent, which was presumably related to the specific lysosomal storage material. Goldin et al. (1999) studied cells from more than 20 ML IV patients, most of them of Ashkenazi Jewish ancestry, who were involved in a longitudinal study conducted at the Clinical Center of the National Institutes of Health. Patients of other ethnic groups included 3 non-Jewish Caucasians and 1 South American Indian. Complementation studies showed that all patients with ML IV, regardless of ancestry or disease severity, have a mutation in the same gene, excluding genetic heterogeneity. In addition Goldin et al. (1999) found high sensitivity to chloroquine in cultured ML IV fibroblasts, which was discovered when different lysosomotropic agents were screened for their ability to kill selectively ML IV fibroblasts in culture. Antimalarial agents with properties similar to chloroquine, such as primaquine or quinacrine, exhibited effects similar to chloroquine, whereas other antimalarial drugs of different chemical structure, such as artemisinin, did not kill fibroblasts even at very high concentrations. </p><p>In fibroblasts from patients with ML IV, Vergarajauregui et al. (2008) observed increased basal levels of autophagy, as evidenced by increased LC3 (MAP1LC3A; 601242) in discrete vesicular structures compared to wildtype fibroblasts. The structures were consistent with autophagosomes, and most of these autophagosomes contained ubiquitinated protein aggregates. Although fusion of autophagosomes with late endosomal lysosomal pathway could occur in ML IV fibroblasts under starvation stress, the process was delayed compared to wildtype fibroblasts. Monitoring of the PDGFR (173410) in MCOLN1-deficient cells showed significantly impaired degradation, indicating that MCOLN1 is required for efficient transport and delivery of material from late endosomes and autophagosomes to lysosomes. Vergarajauregui et al. (2008) suggested that the findings were consistent with a disease model in which abnormal accumulation of ubiquitinated proteins may contribute to neurodegeneration. </p>
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<strong>Mapping</strong>
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<span class="mim-text-font">
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<p>By linkage analysis, Slaugenhaupt et al. (1999) mapped the ML IV locus to chromosome 19p13.3-p13.2 in 13 families. A maximum lod score of 5.51 with no recombination was observed at marker D19S873. Several markers in the linked interval also displayed significant linkage disequilibrium with the disorder. Slaugenhaupt et al. (1999) constructed haplotypes in 26 Ashkenazi Jewish families and demonstrated the existence of 2 founder chromosomes in this population: a major and minor haplotype was observed for 39 (75%) and 11 (21%), respectively, of the 52 chromosomes. </p>
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<span class="mim-font">
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<strong>Inheritance</strong>
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<span class="mim-text-font">
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<p>The transmission pattern of ML4 in the patients reported by Bargal et al. (2000) was consistent with autosomal recessive inheritance. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p>In 21 Ashkenazi Jewish ML IV patients, Bargal et al. (2000) identified 2 mutations in the MCOLN1 gene (605248.0001; 605248.0002) in correlation with the major and minor haplotypes identified by Slaugenhaupt et al. (1999). Six patients were compound heterozygous for both mutations and 2 patients were compound heterozygous for 1 of the founder mutations and a second unidentified mutation. The clinical manifestations of all the patients showed similar severity. </p><p>Sun et al. (2000) identified mutations in the MCOLN1 gene (605248.0004-605248.0006) in patients with ML IV. </p><p>In a 4-year-old girl with ML IV, Goldin et al. (2004) identified compound heterozygous mutations in the MCOLN1 gene (605248.0007-605248.0008). </p><p>In a girl with an unusually mild case of ML IV, who was not of Ashkenazi Jewish origin, Dobrovolny et al. (2007) identified compound heterozygous mutations in the MCOLN1 gene (605248.0005; 605248.0009). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Riedel et al. (1985) stated that 17 cases of ML IV had been reported; about half of them had Ashkenazi Jewish ancestry. </p><p>Chen et al. (1998) stated that over 80% of the patients in whom the diagnosis of ML IV had been made were Ashkenazi Jews, including severely affected and mildly affected patients. </p><p>Raas-Rothschild et al. (1999) interviewed 17 Israeli Ashkenazi families with ML IV patients to study their family origin. Although the families immigrated to Israel from various European countries, they could all trace their roots 3 to 4 generations back to northern Poland or the immediate neighboring country, Lithuania. Furthermore, there are only 1 or 2 ultraorthodox families among the 70 to 80 Ashkenazi families with ML IV patients worldwide, a marked underrepresentation of this group, which constitutes at least 10% of the Ashkenazi population. These data indicated that the ML IV mutation occurred only around the 18th or 19th century after the major expansion of this population, in a founder in this defined European region belonging to a modern, secular family. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<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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</h4>
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</div>
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<span class="mim-text-font">
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<p>Goutieres et al. (1979) suggested that the defect in ML IV may concern ganglioside sialidase (neuraminidase), 95% of which is located in the plasma membrane, the rest in lysosomes. They noted that glycoprotein sialidase was normal. </p><p>Ben-Yoseph et al. (1982) found deficiency of neuraminidase activity toward GD(1a) and GD(1b) gangliosides; parents showed intermediate levels of enzyme activity. Residual enzyme had a K(m) about 18 times higher than that of the normal enzyme. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Unlike other lysosomal storage diseases, ML IV is not associated with a lack of lysosomal hydrolases; instead, ML IV cells display abnormal endocytosis of lipids and accumulate large vesicles, indicating that a defect in endocytosis may underlie the disease. Fares and Greenwald (2001) reported the identification of a loss-of-function mutation in the Caenorhabditis elegans mucolipin-1 homolog, cup5, and showed that this mutation results in an enhanced rate of uptake of fluid-phase markers, decreased degradation of endocytosed protein, and accumulation of large vacuoles. Overexpression of cup5+ causes the opposite phenotype, indicating that cup5 activity controls aspects of endocytosis. The authors concluded that the C. elegans cup5 mutant may be a useful model for studying conserved aspects of mucolipin-1 structure and function and for assessing the effects of potential therapeutic compounds. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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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Bach et al. (1977); Bach et al. (1979); Bach (1979); Dangel et al.
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(1985); Kohn et al. (1977); Lake et al. (1982); Newell et al. (1975);
|
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Zeigler and Bach (1981); Zwaan and Kenyon (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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</div>
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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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<strong>Mucolipidosis type IV: clinical spectrum and natural history.</strong>
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Pediatrics 79: 953-959, 1987.
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Bach, G., Ziegler, M., Kohn, G., Cohen, M. M.
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<strong>Mucopolysaccharidosis accumulation in cultured skin fibroblasts derived from patients with mucolipidosis IV.</strong>
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Am. J. Hum. Genet. 29: 610-618, 1977.
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<strong>Mucolipidosis type IV: ganglioside sialidase deficiency.</strong>
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Chitayat, D., Meunier, C. M., Hodgkinson, K. A., Silver, K., Flanders, M., Anderson, I. J., Little, J. M., Whiteman, D. A. H., Carpenter, S.
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Dobrovolny, R., Liskova, P., Ledvinova, J., Poupetova, H., Asfaw, B., Filipec, M., Jirsova, K., Kraus, J., Elleder, M.
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Goldin, E., Cooney, A., Kaneski, C. R., Brady, R. O., Schiffmann, R.
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<strong>Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV.</strong>
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<p class="mim-text-font">
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<strong>Mucolipidosis IV.</strong>
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[PubMed: 231746]
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<li>
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<p class="mim-text-font">
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Kohn, G., Livni, N., Ornoy, A., Sekeles, E., Beyth, Y., Legum, C., Bach, G., Cohen, M. M.
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<strong>Prenatal diagnosis of mucolipidosis IV by electron microscopy.</strong>
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J. Pediat. 90: 62-66, 1977.
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[PubMed: 830895]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lake, B. D., Milla, P. J., Taylor, D. S. I., Young, E. P.
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<strong>A mild variant of mucolipidosis type 4 (ML4).</strong>
|
|
Birth Defects Orig. Art. Ser. 18(6): 391-404, 1982.
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[PubMed: 7171767]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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|
Merin, S., Livni, N., Berman, E. R., Yatziv, S.
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<strong>Mucolipidosis IV: ocular, systemic, and ultrastructural findings.</strong>
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|
Invest. Ophthal. 14: 437-448, 1975.
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[PubMed: 166049]
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</p>
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<li>
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<p class="mim-text-font">
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Newell, F. W., Matalon, R., Mayer, S.
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<strong>A new mucolipidosis with psychomotor retardation, corneal clouding, and retinal degeneration.</strong>
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Am. J. Ophthal. 80: 440-449, 1975.
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[PubMed: 169696]
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[Full Text: https://doi.org/10.1016/0002-9394(75)90532-2]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Ornoy, A., Arnon, J., Grebner, E. E., Jackson, L. G., Bach, G.
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|
<strong>Early prenatal diagnosis of mucolipidosis IV. (Letter)</strong>
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|
Am. J. Med. Genet. 27: 983-985, 1987.
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[PubMed: 3425607]
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[Full Text: https://doi.org/10.1002/ajmg.1320270429]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Pradhan, S. M., Atchaneeyasakul, L.-O., Appukuttan, B., Mixon, R. N., McFarland, T. J., Billingslea, A. M., Wilson, D. J., Stout, J. T., Weleber, R. G.
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|
<strong>Electronegative electroretinogram in mucolipidosis IV.</strong>
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|
Arch. Ophthal. 120: 45-50, 2002.
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|
[PubMed: 11786056]
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[Full Text: https://doi.org/10.1001/archopht.120.1.45]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Raas-Rothschild, A., Bargal, R., DellaPergola, S., Zeigler, M., Bach, G.
|
|
<strong>Mucolipidosis type IV: the origin of the disease in the Ashkenazi Jewish population.</strong>
|
|
Europ. J. Hum. Genet. 7: 496-498, 1999.
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[PubMed: 10352940]
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Schiffmann, R., Dwyer, N. K., Lubensky, I. A., Tsokos, M., Sutliff, V. E., Latimer, J. S., Frei, K. P., Brady, R. O., Barton, N. W., Blanchette-Mackie, E. J., Goldin, E.
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Sun, M., Goldin, E., Stahl, S., Falardeau, J. L., Kennedy, J. C., Acierno, J. S., Jr., Bove, C., Kaneski, C. R., Nagle, J., Bromley, M.C., Colman, M., Schiffmann, R., Slaugenhaupt, S. A.
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Zwaan, J., Kenyon, K. R.
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<strong>Two brothers with presumed mucolipidosis IV.</strong>
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Birth Defects Orig. Art. Ser. 18(6): 381-390, 1982.
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