4618 lines
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Entry
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- #162400 - NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IA; HSAN1A
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- OMIM
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<p>
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<span class="h4">#162400</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/162400"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS162400"> <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="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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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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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</h4>
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<div><a href="https://clinicaltrials.gov/search?cond=NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IA" 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=10423&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/NBK1390/" 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/5199" 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/hereditary-sensory-neuropathy-type-ia" 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=162400[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=36386" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div class="panel-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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</a>
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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:0070152" 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/162400" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://omia.org/OMIA001150/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0070152" 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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<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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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 230553002, 397734008, 860813007<br />
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<strong>ORPHA:</strong> 36386<br />
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<strong>DO:</strong> 0070152<br />
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">ICD+</a>
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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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162400
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</span>
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</span>
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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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NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IA; HSAN1A
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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HSAN IA<br />
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HSAN1<br />
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NEUROPATHY, HEREDITARY SENSORY, TYPE IA; HSN1A<br />
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HSN IA<br />
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NEUROPATHY, HEREDITARY SENSORY RADICULAR, AUTOSOMAL DOMINANT, TYPE 1A
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</span>
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</h4>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<td>
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<a href="/geneMap/9/301?start=-3&limit=10&highlight=301">
|
|
9q22.31
|
|
</a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Neuropathy, hereditary sensory and autonomic, type IA
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162400"> 162400 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
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|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<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>
|
|
<span class="mim-font">
|
|
SPTLC1
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605712"> 605712 </a>
|
|
</span>
|
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</td>
|
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</tr>
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</tbody>
|
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</table>
|
|
</div>
|
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</div>
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<div>
|
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|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/162400" 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>
|
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|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS162400" 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>
|
|
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|
|
<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/162400" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/162400" 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 dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</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> Ears </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Deafness, sensorineural (reported in 1 family) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60700002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60700002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018784</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span><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">
|
|
|
|
- Macular telangiectasia type 2 (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/823016000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">823016000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5232269&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5232269</a>]</span><br /> -
|
|
Cataracts (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/193570009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">193570009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247053007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247053007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95722004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95722004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H26.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H26.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/366" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/366.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086543</a>, <a href="https://bioportal.bioontology.org/search?q=C0521707&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521707</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Osteomyelitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60168000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60168000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M86.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M86.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M86" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M86</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/730.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">730.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/730.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">730.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029443&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029443</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002754" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002754</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002754" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002754</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Hands </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Osteomyelitis or necrosis, distal, due to sensory neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833221&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833221</a>]</span><br /> -
|
|
Autoamputation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833222&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833222</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001218</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Feet </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Pes cavus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205091006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205091006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/36755004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">36755004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86900005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86900005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/736.73" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.73</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/754.71" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.71</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0728829&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0728829</a>, <a href="https://bioportal.bioontology.org/search?q=C0039273&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039273</a>, <a href="https://bioportal.bioontology.org/search?q=C2239098&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2239098</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001761</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001761</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2ad12e53b20f47e5685234fa29da6610" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Pes_Cavus-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2ad12e53b20f47e5685234fa29da6610" 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 /> -
|
|
Osteomyelitis or necrosis, distal, due to sensory neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833221&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833221</a>]</span><br /> -
|
|
Autoamputation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833222&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833222</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001218</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Ulcers, distal, painless, due to sensory neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834201&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834201</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Peripheral Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Distal sensory loss of all modalities (pain, temperature, touch, vibration) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834189&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834189</a>]</span><br /> -
|
|
Taste is spared <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834190&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834190</a>]</span><br /> -
|
|
Sharp, 'lightning'-like pain <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834191&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834191</a>]</span><br /> -
|
|
Distal limb muscular atrophy due to peripheral neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834192&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834192</a>]</span><br /> -
|
|
Distal limb muscular weakness due to peripheral neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834193&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834193</a>]</span><br /> -
|
|
Distal hyporeflexia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834194&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834194</a>]</span><br /> -
|
|
Distal areflexia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834195&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834195</a>]</span><br /> -
|
|
Lower limbs more severely affected than upper limbs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277209</a>]</span><br /> -
|
|
Autonomic involvement is variable <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277210&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277210</a>]</span><br /> -
|
|
Motor involvement is variable <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277211&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277211</a>]</span><br /> -
|
|
Axonal neuropathy, chronic, seen on EMG <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5232266&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5232266</a>]</span><br /> -
|
|
Decreased sensory nerve action potentials <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850305&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850305</a>]</span><br /> -
|
|
Dorsal spinal columns are diminished in size <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834197&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834197</a>]</span><br /> -
|
|
Dorsal nerve roots and ganglia cells show degenerative changes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834198&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834198</a>]</span><br /> -
|
|
Distal nerve biopsy shows decreased numbers of small myelinated and unmyelinated fibers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834199&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834199</a>]</span><br /> -
|
|
Loss of large myelinated fibers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859606&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859606</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003387" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003387</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003387" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003387</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset usually in the second to fourth decades of life<br /> -
|
|
Some patients with childhood onset and a more severe phenotype have been reported<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the long-chain base subunit 1 of the serine palmitoyltransferase gene (SPTLC1, <a href="/entry/605712#0001">605712.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Hereditary sensory and autonomic neuropathy
|
|
- <a href="/phenotypicSeries/PS162400">PS162400</a>
|
|
- 16 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/949?start=-3&limit=10&highlight=949"> 1p13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608654"> Neuropathy, hereditary sensory and autonomic, type V </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">
|
|
<a href="/entry/608654"> 608654 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162030"> NGF </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/162030"> 162030 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1269?start=-3&limit=10&highlight=1269"> 1q23.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/256800"> Insensitivity to pain, congenital, with anhidrosis </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">
|
|
<a href="/entry/256800"> 256800 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/191315"> NTRK1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/191315"> 191315 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/1177?start=-3&limit=10&highlight=1177"> 2q37.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614213"> Neuropathy, hereditary sensory, type IIC </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">
|
|
<a href="/entry/614213"> 614213 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601255"> KIF1A </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601255"> 601255 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/104?start=-3&limit=10&highlight=104"> 3p24-p22 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608088"> Neuropathy, hereditary sensory, type IB </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608088"> 608088 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608088"> HSN1B </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608088"> 608088 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/183?start=-3&limit=10&highlight=183"> 3p22.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615548"> Neuropathy, hereditary sensory and autonomic, type VII </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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">
|
|
<a href="/entry/615548"> 615548 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604385"> SCN11A </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604385"> 604385 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/5/67?start=-3&limit=10&highlight=67"> 5p15.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613115"> Neuropathy, hereditary sensory and autonomic, type IIB </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>
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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/613115"> 613115 </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/613114"> RETREG1 </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/613114"> 613114 </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/6/611?start=-3&limit=10&highlight=611"> 6p12.1 </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/614653"> Neuropathy, hereditary sensory and autonomic, type VI </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/614653"> 614653 </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/113810"> DST </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/113810"> 113810 </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/9/301?start=-3&limit=10&highlight=301"> 9q22.31 </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/162400"> Neuropathy, hereditary sensory and autonomic, type IA </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 dominant">AD</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/162400"> 162400 </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/605712"> SPTLC1 </a>
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</span>
|
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</td>
|
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<td>
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<span class="mim-font">
|
|
<a href="/entry/605712"> 605712 </a>
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</span>
|
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</td>
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</tr>
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<tr>
|
|
<td>
|
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<span class="mim-font">
|
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<a href="/geneMap/9/397?start=-3&limit=10&highlight=397"> 9q31.3 </a>
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|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/223900"> Dysautonomia, familial </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">
|
|
<a href="/entry/223900"> 223900 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603722"> ELP1 </a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603722"> 603722 </a>
|
|
</span>
|
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</td>
|
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</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/9/579?start=-3&limit=10&highlight=579"> 9q34.12 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616488"> Neuropathy, hereditary sensory and autonomic, type VIII </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">
|
|
<a href="/entry/616488"> 616488 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616458"> PRDM12 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616458"> 616458 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/528?start=-3&limit=10&highlight=528"> 11q13.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615632"> Neuropathy, hereditary sensory, type IF </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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">
|
|
<a href="/entry/615632"> 615632 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609369"> ATL3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609369"> 609369 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/12/10?start=-3&limit=10&highlight=10"> 12p13.33 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/201300"> Neuropathy, hereditary sensory and autonomic, type II </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">
|
|
<a href="/entry/201300"> 201300 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605232"> WNK1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605232"> 605232 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/225?start=-3&limit=10&highlight=225"> 14q22.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613708"> Neuropathy, hereditary sensory, type ID </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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">
|
|
<a href="/entry/613708"> 613708 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606439"> ATL1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606439"> 606439 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/419?start=-3&limit=10&highlight=419"> 14q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613640"> Neuropathy, hereditary sensory and autonomic, type IC </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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">
|
|
<a href="/entry/613640"> 613640 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605713"> SPTLC2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605713"> 605713 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/564?start=-3&limit=10&highlight=564"> 14q32.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615031"> Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay </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">
|
|
<a href="/entry/615031"> 615031 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615000"> TECPR2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615000"> 615000 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/260?start=-3&limit=10&highlight=260"> 19p13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614116"> Neuropathy, hereditary sensory, type IE </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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">
|
|
<a href="/entry/614116"> 614116 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/126375"> DNMT1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/126375"> 126375 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
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</div>
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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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</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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<br />
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</div>
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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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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because hereditary sensory neuropathy type IA (HSAN1A) is caused by heterozygous mutation in the SPTLC1 gene (<a href="/entry/605712">605712</a>) on chromosome 9q22.</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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<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>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Hereditary sensory and autonomic neuropathy type IA (HSAN1A) is an autosomal dominant neurologic disorder characterized by sensory neuropathy with variable autonomic and motor involvement. Most patients have adult onset of slowly progressive distal sensory impairment manifest as numbness, tingling, or pain, as well as distal muscle atrophy. Complications include ulceration and osteomyelitis. Some patients may have a more severe phenotype with onset in childhood. Electrophysiologic studies show a predominantly axonal neuropathy with some demyelinating features. Some patients may have evidence of central nervous system involvement, including macular telangiectasia type 2. Affected individuals have increased levels of plasma 1-deoxysphingolipids (1-deoxySLs), which are thought to be neurotoxic (summary by <a href="#31" class="mim-tip-reference" title="Rotthier, A., Auer-Grumbach, M., Janssens, K., Baets, J., Penno, A., Almeida-Souza, L., Van Hoof, K., Jacobs, A., De Vriendt, E., Schlotter-Weigel, B., Loscher, W., Vondracek, P., Seeman, P., De Jonghe, P., Van Dijck, P., Jordanova, A., Hornemann, T., Timmerman, V. <strong>Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I.</strong> Am. J. Hum. Genet. 87: 513-522, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20920666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20920666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20920666[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2010.09.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20920666">Rotthier et al., 2010</a> and <a href="#18" class="mim-tip-reference" title="Gantner, M. L., Eade, K., Wallace, M., Handzlik, M. K., Fallon, R., Trombley, J., Bonelli, R., Giles, S., Harkins-Perry, S., Heeren, T. F C., Sauer, L., Ideguchi, Y., and 20 others. <strong>Serine and lipid metabolism in macular disease and peripheral neuropathy.</strong> New Eng. J. Med. 381: 1422-1433, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31509666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31509666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31509666[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/10.1056/NEJMoa1815111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31509666">Gantner et al., 2019</a>). Oral supplementation with serine decreases 1-deoxySL and may offer some clinical benefits (<a href="#16" class="mim-tip-reference" title="Fridman, V., Suriyanarayanan, S., Novak, P., David, W., Macklin, E. A., McKenna-Yasek, D., Walsh, K., Aziz-Bose, R., Oaklander, A. L., Brown, R., Hornemann, T., Eichler, F. <strong>Randomized trial of I-serine in patients with hereditary sensory and autonomic neuropathy type 1.</strong> Neurology 92: e359-e370, 2019. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30626650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30626650</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30626650[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/10.1212/WNL.0000000000006811" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30626650">Fridman et al., 2019</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=31509666+30626650+20920666" 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>Genetic Heterogeneity of Hereditary Sensory and Autonomic Neuropathy</em></strong></p><p>
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See also HSAN1C (<a href="/entry/613640">613640</a>), caused by mutation in the SPTLC2 gene (<a href="/entry/605713">605713</a>) on 14q24; HSN1D (<a href="/entry/613708">613708</a>), caused by mutation in the ATL1 gene (<a href="/entry/606439">606439</a>) on 14q22; HSN1E (<a href="/entry/614116">614116</a>), caused by mutation in the DNMT1 gene (<a href="/entry/126375">126375</a>) on 19p13; HSN1F (<a href="/entry/615632">615632</a>), caused by mutation in the ATL3 gene (<a href="/entry/609369">609369</a>) on 11q13; HSAN2A (<a href="/entry/201300">201300</a>), caused by mutation in the HSN2 isoform of the WNK1 gene (<a href="/entry/605232">605232</a>) on 12p13; HSAN2B (<a href="/entry/613115">613115</a>), caused by mutation in the FAM134B gene (<a href="/entry/613114">613114</a>) on 5p15; HSN2C (<a href="/entry/614213">614213</a>), caused by mutation in the KIF1A gene (<a href="/entry/601255">601255</a>) on 2q37; HSAN2D (see <a href="/entry/243000">243000</a>), caused by mutation in the SCN9A gene (<a href="/entry/603415">603415</a>) on 2q24; HSAN3 (<a href="/entry/223900">223900</a>), caused by mutation in the ELP1 gene (<a href="/entry/603722">603722</a>) on 9q31; HSAN4 (<a href="/entry/256800">256800</a>), caused by mutation in the NTRK1 gene (<a href="/entry/191315">191315</a>) on 1q23; HSAN5 (<a href="/entry/608654">608654</a>), caused by mutation in the NGF gene (<a href="/entry/162030">162030</a>) on 1p13; HSAN6 (<a href="/entry/614653">614653</a>), caused by mutation in the DST gene (<a href="/entry/113810">113810</a>) on 6p12; HSAN7 (<a href="/entry/615548">615548</a>), caused by mutation in the SCN11A gene (<a href="/entry/604385">604385</a>) on 3p22; and HSAN8 (<a href="/entry/616488">616488</a>), caused by mutation in the PRDM12 gene (<a href="/entry/616458">616458</a>) on chromosome 9q34.</p><p>Adult-onset HSAN with anosmia (<a href="/entry/608720">608720</a>) may be another distinct form of HSAN, and HSAN1B (<a href="/entry/608088">608088</a>) with cough and gastroesophageal reflux maps to chromosome 3p24-p22.</p>
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<p><a href="#20" class="mim-tip-reference" title="Hicks, E. P. <strong>Hereditary perforating ulcer of the foot.</strong> Lancet 199: 319-321, 1922. Note: Originally Volume I."None>Hicks (1922)</a> described an English family in which 10 members suffered from perforating ulcers of the feet, shooting pains, and deafness. Age of onset ranged from 15 to 36 years. Presentation was usually with a corn on a big toe followed by a painless ulcer with bony debris. Patients later experienced shooting pains similar to the lightning pains of tabes dorsalis and developed bilateral deafness progressing to total deafness over several years. Neurologic examination showed disappearance of ankle and knee jerks and absence of an extensor plantar response. There was loss of pain, touch, heat, and cold sensation over the feet, but sensation of the arms remained normal. Cranial nerves were normal, with the exception of the auditory nerve, pupils reacted normally, and there was no nystagmus. <a href="#20" class="mim-tip-reference" title="Hicks, E. P. <strong>Hereditary perforating ulcer of the foot.</strong> Lancet 199: 319-321, 1922. Note: Originally Volume I."None>Hicks (1922)</a> noted that although hereditary perforating ulcers of the feet had been reported in patients in the past, there had been no previous mention of accompanying deafness or shooting pains. <a href="#11" class="mim-tip-reference" title="Denny-Brown, D. <strong>Hereditary sensory radicular neuropathy.</strong> J. Neurol. Neurosurg. Psychiat. 14: 237-252, 1951.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14898294/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14898294</a>] [<a href="https://doi.org/10.1136/jnnp.14.4.237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14898294">Denny-Brown (1951)</a> reported the clinical and autopsy findings of a 53-year-old woman who was a member of the family reported by <a href="#20" class="mim-tip-reference" title="Hicks, E. P. <strong>Hereditary perforating ulcer of the foot.</strong> Lancet 199: 319-321, 1922. Note: Originally Volume I."None>Hicks (1922)</a>. When she was 22 years of age, an ulcer formed on her right great toe, requiring a year to heal. She subsequently suffered from recurrent ulceration, each episode lasting 6 to 9 months and sometimes extending to bone. In her early twenties, she first noticed shooting pains in her legs, sometimes in her arms. Deafness began at the age of 40 years and progressed to almost total deafness by 53 years of age. Neurologic examination at 53 years of age showed loss of all sensation in the lower legs, with loss of pain and temperature sensation in the thighs and hands. Autopsy showed a small brain and marked loss of ganglion cells in the sacral and lumbar dorsal root ganglia. Remaining ganglion cells showed proliferation of subcapsular dendrites and hyaline bodies, possibly representing an amyloid mass around capillaries. There were less severe changes in C-8 and T-1 ganglia. The affected families reported by <a href="#15" class="mim-tip-reference" title="Ervin, F. R., Sternbach, R. A. <strong>Hereditary insensitivity to pain.</strong> Trans. Am. Neurol. Assoc. 85: 70-74, 1960.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13890708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13890708</a>]" pmid="13890708">Ervin and Sternbach (1960)</a> and <a href="#34" class="mim-tip-reference" title="Silverman, F. N., Gilden, J. J. <strong>Congenital insensitivity to pain, a neurologic syndrome with bizarre skeletal lesions.</strong> Radiology 72: 176-190, 1959.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13634374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13634374</a>] [<a href="https://doi.org/10.1148/72.2.176" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13634374">Silverman and Gilden (1959)</a> appeared to show autosomal dominant inheritance. <a href="#24" class="mim-tip-reference" title="Mandell, A. J., Smith, C. K. <strong>Hereditary sensory radicular neuropathy.</strong> Neurology 10: 627-630, 1960.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14420561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14420561</a>] [<a href="https://doi.org/10.1212/wnl.10.7.627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14420561">Mandell and Smith (1960)</a> observed sensory radicular neuropathy in 3 generations of a family. Clinical features included neuropathic arthropathy, recurrent ulceration of the lower extremities, and signs of radicular sensory deficiency in both the upper and the lower extremities without any motor dysfunction. <a href="#13" class="mim-tip-reference" title="Dyck, P. J., Kennel, A. J., Magal, I. V., Kraybill, E. N. <strong>A Virginia kinship with hereditary sensory neuropathy: peroneal muscular atrophy and pes cavus.</strong> Mayo Clin. Proc. 40: 685-694, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14341177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14341177</a>]" pmid="14341177">Dyck et al. (1965)</a> described a family with sensory neuropathy accompanied by peroneal muscular atrophy and pes cavus. <a href="#6" class="mim-tip-reference" title="Campbell, A. M. G., Hoffman, H. L. <strong>Sensory radicular neuropathy associated with muscle wasting in two cases.</strong> Brain 87: 67-74, 1964.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14152213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14152213</a>] [<a href="https://doi.org/10.1093/brain/87.1.67" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14152213">Campbell and Hoffman (1964)</a> and <a href="#10" class="mim-tip-reference" title="DeLeon, G. A. <strong>Progressive ventral sensory loss in sensory radicular neuropathy and hypertrophic neuritis.</strong> Johns Hopkins Med. J. 125: 53-61, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4310511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4310511</a>]" pmid="4310511">DeLeon (1969)</a> also reported cases in which amyotrophy was a feature. Using a cholinesterase technique on skin biopsies from the pad of the great toe of affected persons, <a href="#13" class="mim-tip-reference" title="Dyck, P. J., Kennel, A. J., Magal, I. V., Kraybill, E. N. <strong>A Virginia kinship with hereditary sensory neuropathy: peroneal muscular atrophy and pes cavus.</strong> Mayo Clin. Proc. 40: 685-694, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14341177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14341177</a>]" pmid="14341177">Dyck et al. (1965)</a> found normal numbers of Meissner corpuscles in a 14-year-old boy with early signs suggestive of the disorder, but no corpuscles in a 37-year-old man and a 28-year-old woman with well-developed disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14152213+14420561+14341177+13634374+14898294+4310511+13890708" 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="Dyck, P. J., Low, P. A., Stevens, J. C. <strong>'Burning feet' as the only manifestation of dominantly inherited sensory neuropathy.</strong> Mayo Clin. Proc. 58: 426-429, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6575233/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6575233</a>]" pmid="6575233">Dyck et al. (1983)</a> noted that 'burning feet' may be the only manifestation of dominantly inherited sensory neuropathy. The symptoms are ameliorated by cold and aggravated by heat. Restless legs and lancinating pain are other presentations of the disorder, which often resulted in severe distal sensory loss, mutilating acropathy, and neurotrophic arthropathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6575233" 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 detailed clinical study of a patient with HSN1, including audiometric testing, autonomic functions, electromyography, transcranial magnetic stimulation, and brain imaging, <a href="#19" class="mim-tip-reference" title="Hageman, G., Hilhorst, B. G. J., Rozeboom, A. R. <strong>Is there involvement of the central nervous system in hereditary sensory radicular neuropathy?</strong> Clin. Neurol. Neurosurg. 94: 49-54, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1321699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1321699</a>] [<a href="https://doi.org/10.1016/0303-8467(92)90119-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1321699">Hageman et al. (1992)</a> determined that there were no signs of central nervous system involvement and stated that HSN1 is a disorder of the dorsal root ganglia and peripheral nerves. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1321699" 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>Wallace (<a href="#38" class="mim-tip-reference" title="Wallace, D. C. <strong>A Study of an Hereditary Neuropathy.</strong> Thesis: Univ. of Sydney (pub.) 1968."None>1968</a>, <a href="#39" class="mim-tip-reference" title="Wallace, D. C. <strong>Hereditary sensory radicular neuropathy. In: Archdall Medical Monograph 8.</strong> Sydney: Australasian Med. Pub. Co. 1970."None>1970</a>) studied an extensively affected Australian kindred. In a study of this kindred and 3 other Australian kindreds with HSAN1, <a href="#28" class="mim-tip-reference" title="Nicholson, G. A., Dawkins, J. L., Blair, I. P., Kennerson, M. L., Gordon, M. J., Cherryson, A. K., Nash, J., Bananis, T. <strong>The gene for hereditary sensory neuropathy type I (HSN-1) maps to chromosome 9q22.1-q22.3.</strong> Nature Genet. 13: 101-104, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673084</a>] [<a href="https://doi.org/10.1038/ng0596-101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673084">Nicholson et al. (1996)</a> found that a typical history included lightning pains, painless skin injuries and ulceration, and signs including distal sensory loss to sharp, hot, and cold sensation, with loss of distal reflexes and distal muscle wasting. Nerve conduction velocities showed an axonal neuropathy, particularly of the lower limbs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673084" 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="Dubourg, O., Barhoumi, C., Azzedine, H., Birouk, N., Brice, A., Bouche, P., Leguern, E. <strong>Phenotypic and genetic study of a family with hereditary sensory neuropathy and prominent weakness.</strong> Muscle Nerve 23: 1508-1514, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11003785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11003785</a>] [<a href="https://doi.org/10.1002/1097-4598(200010)23:10<1508::aid-mus6>3.0.co;2-d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11003785">Dubourg et al. (2000)</a> reported a French family with autosomal dominant hereditary sensory neuropathy suggestive of linkage to chromosome 9q. Mean age at onset was 34 years. All patients presented with distal sensory loss and distal muscle weakness of both the upper and lower limbs. Four patients had foot ulcerations, and 3 patients had hyperhidrosis. Motor nerve conduction velocities were normal or mildly decreased, consistent with an axonal neuropathy. Sensory nerve action potentials were either reduced or could not be recorded. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11003785" 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>Severe Phenotype</em></strong></p><p>
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<a href="#32" class="mim-tip-reference" title="Rotthier, A., Baets, J., De Vriendt, E., Jacobs, A., Auer-Grumbach, M., Levy, N., Bonello-Palot, N., Kilic, S. S., Weis, J., Nascimento, A., Swinkels, M., Kruyt, M. C., Jordanova, A., De Jonghe, P., Timmerman, V. <strong>Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.</strong> Brain 132: 2699-2711, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19651702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19651702</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19651702[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/brain/awp198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19651702">Rotthier et al. (2009)</a> reported a French Gypsy patient with an unusually severe form of HSAN1. The patient had congenital insensitivity to pain with eschar and foot ulceration, pes cavus/equinovarus, vocal cord paralysis, and gastroesophageal reflux. The patient also had severe growth and mental retardation, microcephaly, hypotonia, amyotrophy, and respiratory insufficiency. Nerve conduction studies showed absent sensory and motor responses in the upper and lower limbs. Genetic analysis identified a de novo heterozygous mutation in the SPTLC1 gene (S331F; <a href="/entry/605712#0005">605712.0005</a>). The phenotype expanded the clinical spectrum of HSAN1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19651702" 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="Auer-Grumbach, M., Bode, H., Pieber, T. R., Schabhuttl, M., Fischer, D., Seidl, R., Graf, E., Wieland, T., Schuh, R., Vacariu, G., Grill, F., Timmerman, V., Strom, T. M., Hornemann, T. <strong>Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype.</strong> Europ. J. Med. Genet. 56: 266-269, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23454272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23454272</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23454272[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ejmg.2013.02.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23454272">Auer-Grumbach et al. (2013)</a> reported that a patient (ER-CIPA-20374) described by <a href="#22" class="mim-tip-reference" title="Huehne, K., Zweier, C., Raab, K., Odent, S., Bonnaure-Mallet, M., Sixou, J. L., Landrieu, P., Goizet, C., Sarlangue, J., Baumann, M., Eggermann, T., Rauch, A., Ruppert, S., Stettner, G. M., Rautenstrauss, B. <strong>Novel missense, insertion and deletion mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with congenital insensitivity to pain with anhidrosis.</strong> Neuromusc. Disord. 18: 159-166, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18077166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18077166</a>] [<a href="https://doi.org/10.1016/j.nmd.2007.10.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18077166">Huehne et al. (2008)</a> with a severe form of HSAN1 had the same heterozygous S331F mutation in the SPTLC1 gene as that reported by <a href="#32" class="mim-tip-reference" title="Rotthier, A., Baets, J., De Vriendt, E., Jacobs, A., Auer-Grumbach, M., Levy, N., Bonello-Palot, N., Kilic, S. S., Weis, J., Nascimento, A., Swinkels, M., Kruyt, M. C., Jordanova, A., De Jonghe, P., Timmerman, V. <strong>Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.</strong> Brain 132: 2699-2711, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19651702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19651702</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19651702[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/brain/awp198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19651702">Rotthier et al. (2009)</a> in a patient with early-onset severe HSAN1A. The patient described by <a href="#22" class="mim-tip-reference" title="Huehne, K., Zweier, C., Raab, K., Odent, S., Bonnaure-Mallet, M., Sixou, J. L., Landrieu, P., Goizet, C., Sarlangue, J., Baumann, M., Eggermann, T., Rauch, A., Ruppert, S., Stettner, G. M., Rautenstrauss, B. <strong>Novel missense, insertion and deletion mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with congenital insensitivity to pain with anhidrosis.</strong> Neuromusc. Disord. 18: 159-166, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18077166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18077166</a>] [<a href="https://doi.org/10.1016/j.nmd.2007.10.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18077166">Huehne et al. (2008)</a> and <a href="#1" class="mim-tip-reference" title="Auer-Grumbach, M., Bode, H., Pieber, T. R., Schabhuttl, M., Fischer, D., Seidl, R., Graf, E., Wieland, T., Schuh, R., Vacariu, G., Grill, F., Timmerman, V., Strom, T. M., Hornemann, T. <strong>Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype.</strong> Europ. J. Med. Genet. 56: 266-269, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23454272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23454272</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23454272[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ejmg.2013.02.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23454272">Auer-Grumbach et al. (2013)</a> had onset in early childhood or muscle weakness and hypotrophy in addition to prominent sensory disturbances, bone fractures, and osteomyelitis. The patient developed cataract at age 9 years, complete retinal detachment at age 10, and repetitive corneal ulceration and keratitis with poor wound healing. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23454272+18077166+19651702" 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 another patient with a severe form of HSAN1, <a href="#1" class="mim-tip-reference" title="Auer-Grumbach, M., Bode, H., Pieber, T. R., Schabhuttl, M., Fischer, D., Seidl, R., Graf, E., Wieland, T., Schuh, R., Vacariu, G., Grill, F., Timmerman, V., Strom, T. M., Hornemann, T. <strong>Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype.</strong> Europ. J. Med. Genet. 56: 266-269, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23454272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23454272</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23454272[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ejmg.2013.02.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23454272">Auer-Grumbach et al. (2013)</a> identified a different de novo heterozygous mutation at the same codon (S331Y; <a href="/entry/605712#0007">605712.0007</a>). This patient had onset at age 4 years of unsteady gait, hand tremor, mild sensory disturbances, and a pes cavus foot deformity necessitating triple arthrodesis at age 5. At examination at age 12, there was general muscle hypotrophy and hypotonia with pronounced weakness in the distal muscles of the upper and lower limbs. There were prominent sensory disturbances; these were pronounced in the feet and affected all qualities except for the vibration sense, which remained completely preserved. At the toes, scars from burns due to reduced pain and temperature sensation were evident. There was also hypermobility of the joints, bilateral hand tremor, and fasciculations, most prominent in the tongue. At age 13, she developed bilateral cataracts. Disease progression was rapid and led to severe scoliosis, respiratory problems, and wheelchair dependence at age 14. The patient had prominent growth retardation but normal intellectual development. The level of 1-deoxySL was significantly elevated in the patient's plasma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23454272" 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>Association with Macular Telangiectasia Type 2</em></strong></p><p>
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<a href="#18" class="mim-tip-reference" title="Gantner, M. L., Eade, K., Wallace, M., Handzlik, M. K., Fallon, R., Trombley, J., Bonelli, R., Giles, S., Harkins-Perry, S., Heeren, T. F C., Sauer, L., Ideguchi, Y., and 20 others. <strong>Serine and lipid metabolism in macular disease and peripheral neuropathy.</strong> New Eng. J. Med. 381: 1422-1433, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31509666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31509666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31509666[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/10.1056/NEJMoa1815111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31509666">Gantner et al. (2019)</a> identified 9 patients, including 8 patients from 2 unrelated families and an additional unrelated patient, with genetically confirmed HSAN1A who also had type 2 macular telangiectasia. All carried the same heterozygous C133Y mutation in the SPTLC1 gene (<a href="/entry/605712#0001">605712.0001</a>). The proband in the first family presented with bilateral bull's eye maculopathy at 21 years of age. Detailed ophthalmologic examination showed findings diagnostic for macular telangiectasia type 2, including parafoveal telangiectatic retinal vessels, 'right angle' venules, retinal opacification, pigment clumping, low levels of macular carotenoid pigment, leakage on fluorescein angiography, blue light-reflectance abnormalities, and intraretinal cysts and ellipsoid zone defects on optical coherence tomography (OCT). His father and sister had similar ocular findings, although the features in the sister were milder. None of these patients had received serine supplementation. All 3 patients had also been diagnosed clinically with a peripheral neuropathy, although details of the neuropathy were not provided. After exome sequencing identified the SPTLC1 mutation in this family, <a href="#18" class="mim-tip-reference" title="Gantner, M. L., Eade, K., Wallace, M., Handzlik, M. K., Fallon, R., Trombley, J., Bonelli, R., Giles, S., Harkins-Perry, S., Heeren, T. F C., Sauer, L., Ideguchi, Y., and 20 others. <strong>Serine and lipid metabolism in macular disease and peripheral neuropathy.</strong> New Eng. J. Med. 381: 1422-1433, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31509666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31509666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31509666[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/10.1056/NEJMoa1815111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31509666">Gantner et al. (2019)</a> examined additional patients with HSAN1 for macular telangiectasia. Five patients from family 2 and an unrelated woman (patient 1), all of whom also carried the C133Y SPTLC1 mutation, were similarly affected. The individuals from family 2 and patient 1 had received serine supplementation. Two additional unrelated patients (patients 2 and 3), who had HSAN1A due to a heterozygous C133W mutation in the SPTLC1 gene (<a href="/entry/605712#0002">605712.0002</a>), did not have macular telangiectasia. However, both patients were under the age of 50 and had been treated with serine supplementation. Two patients from another family (family 3) with HSAN1C (<a href="/entry/613610">613610</a>) due to a heterozygous S384F missense mutation in the SPTLC2 gene (<a href="/entry/605713#0005">605713.0005</a>) also had macular telangiectasia; they had not received serine supplementation. <a href="#18" class="mim-tip-reference" title="Gantner, M. L., Eade, K., Wallace, M., Handzlik, M. K., Fallon, R., Trombley, J., Bonelli, R., Giles, S., Harkins-Perry, S., Heeren, T. F C., Sauer, L., Ideguchi, Y., and 20 others. <strong>Serine and lipid metabolism in macular disease and peripheral neuropathy.</strong> New Eng. J. Med. 381: 1422-1433, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31509666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31509666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31509666[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/10.1056/NEJMoa1815111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31509666">Gantner et al. (2019)</a> noted that the macular phenotype in patients with HSAN1A and HSAN1C was typical of that observed in those with isolated macular telangiectasia. Moreover, previous studies (see, e.g., <a href="#30" class="mim-tip-reference" title="Penno, A., Reilly, M. M., Houlden, H., Laura, M., Rentsch, K., Niederkofler, V., Stoeckli, E. T., Nicholson, G., Eichler, F., Brown, R. H., Jr., von Eckardstein, A., Hornemann, T. <strong>Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids.</strong> J. Biol. Chem. 285: 11178-11187, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20097765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20097765</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20097765[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/10.1074/jbc.M109.092973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20097765">Penno et al., 2010</a>, <a href="#31" class="mim-tip-reference" title="Rotthier, A., Auer-Grumbach, M., Janssens, K., Baets, J., Penno, A., Almeida-Souza, L., Van Hoof, K., Jacobs, A., De Vriendt, E., Schlotter-Weigel, B., Loscher, W., Vondracek, P., Seeman, P., De Jonghe, P., Van Dijck, P., Jordanova, A., Hornemann, T., Timmerman, V. <strong>Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I.</strong> Am. J. Hum. Genet. 87: 513-522, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20920666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20920666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20920666[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2010.09.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20920666">Rotthier et al., 2010</a>, <a href="#5" class="mim-tip-reference" title="Bode, H., Bourquin, F., Suriyanarayanan, S., Wei, Y., Alecu, I., Othman, A., Von Eckardstein, A., Hornemann, T. <strong>HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship.</strong> Hum. Molec. Genet. 25: 853-865, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26681808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26681808</a>] [<a href="https://doi.org/10.1093/hmg/ddv611" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26681808">Bode et al., 2016</a>) had demonstrated that mutations in these genes result in abnormal accumulation of neurotoxic deoxysphingolipids. There was a dose-response effect. Studies in mouse models and in cell-based retinal organoids demonstrated that low serine levels were associated with increased deoxysphingolipids that were toxic to photoreceptor cells in the retina and caused peripheral sensory deficits; the main neurotoxic species was identified as deoxydihydroceramide. Overall, the findings provided a link between altered serine and lipid metabolism, whether caused by an identified genetic defect or unknown factors, and peripheral neuropathy as well as macular telangiectasia type 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26681808+31509666+20097765+20920666" 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 HSAN1A in the families reported by <a href="#9" class="mim-tip-reference" title="Dawkins, J. L., Hulme, D. J., Brahmbhatt, S. B., Auer-Grumbach, M., Nicholson, G. A. <strong>Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I.</strong> Nature Genet. 27: 309-312, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242114</a>] [<a href="https://doi.org/10.1038/85879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11242114">Dawkins et al. (2001)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242114" 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="#28" class="mim-tip-reference" title="Nicholson, G. A., Dawkins, J. L., Blair, I. P., Kennerson, M. L., Gordon, M. J., Cherryson, A. K., Nash, J., Bananis, T. <strong>The gene for hereditary sensory neuropathy type I (HSN-1) maps to chromosome 9q22.1-q22.3.</strong> Nature Genet. 13: 101-104, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673084</a>] [<a href="https://doi.org/10.1038/ng0596-101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673084">Nicholson et al. (1996)</a> undertook a genomewide linkage screen in 4 Australian kindreds with hereditary sensory neuropathy, including 1 family that had been reported by <a href="#23" class="mim-tip-reference" title="Jackson, M. <strong>Familial lumbo-sacral syringomyelia and the significance of developmental errors of the spinal cord and column.</strong> Med. J. Aust. 1: 434-439, 1949."None>Jackson (1949)</a> and followed up by Wallace (<a href="#38" class="mim-tip-reference" title="Wallace, D. C. <strong>A Study of an Hereditary Neuropathy.</strong> Thesis: Univ. of Sydney (pub.) 1968."None>1968</a>, <a href="#39" class="mim-tip-reference" title="Wallace, D. C. <strong>Hereditary sensory radicular neuropathy. In: Archdall Medical Monograph 8.</strong> Sydney: Australasian Med. Pub. Co. 1970."None>1970</a>). <a href="#28" class="mim-tip-reference" title="Nicholson, G. A., Dawkins, J. L., Blair, I. P., Kennerson, M. L., Gordon, M. J., Cherryson, A. K., Nash, J., Bananis, T. <strong>The gene for hereditary sensory neuropathy type I (HSN-1) maps to chromosome 9q22.1-q22.3.</strong> Nature Genet. 13: 101-104, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673084</a>] [<a href="https://doi.org/10.1038/ng0596-101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673084">Nicholson et al. (1996)</a> found that the disease locus, which they symbolized HSN1, mapped to an 8-cM region flanked by D9S318 and D9S176 on 9q22.1-q22.3. Multipoint linkage analysis suggested a most likely location at D9S287, within a 4.9-cM confidence interval. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Blair, I. P., Dawkins, J. L., Nicholson, G. A. <strong>Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q21.1-q22.3: exclusion of GAS1 and XPA.</strong> Cytogenet. Cell Genet. 78: 140-141, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371409</a>] [<a href="https://doi.org/10.1159/000134649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9371409">Blair et al. (1997)</a> refined the mapping of HSN1 to a 3- to 4-cM interval within the 9q22.1-q22.3 region, and excluded GAS1 (<a href="/entry/139185">139185</a>) and XPA (<a href="/entry/611153">611153</a>) as candidate genes. Using composite mapping data, <a href="#4" class="mim-tip-reference" title="Blair, I. P., Hulme, D., Dawkins, J. L., Nicholson, G. A. <strong>A YAC-based transcript map of human chromosome 9q22.1-q22.3 encompassing the loci for hereditary sensory neuropathy type I and multiple self-healing squamous epithelioma.</strong> Genomics 51: 277-281, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9722951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9722951</a>] [<a href="https://doi.org/10.1006/geno.1998.5373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9722951">Blair et al. (1998)</a> estimated the HSN1 critical region, flanked by D9S1781 and FB19B7, at 3 to 4 Mb. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9722951+9371409" 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 studies of Chinese hamster ovary (CHO) cells and yeast, <a href="#17" class="mim-tip-reference" title="Gable, K., Gupta, S. D., Han, G., Niranjanakumari, S., Harmon, J. M., Dunn, T. M. <strong>A disease-causing mutation in the active site of serine palmitoyltransferase causes catalytic promiscuity.</strong> J. Biol. Chem. 285: 22846-22852, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20504773/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20504773</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20504773[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/10.1074/jbc.M110.122259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20504773">Gable et al. (2010)</a> demonstrated that the mutant SPTLC1 C133W protein (<a href="/entry/605712#0002">605712.0002</a>) provided sufficient SPT activity to support growth, although total enzyme activity was only 10 to 20% of wildtype. Yeast and CHO cells expressing the C133W mutant along with SPTLC2 (<a href="/entry/605713">605713</a>) and SSSPTA (<a href="/entry/613540">613540</a>) or SSSPTB (<a href="/entry/610412">610412</a>) showed a preferential condensation of palmitoyl-CoA to alanine rather than serine. These results were not found with wildtype SPTLC1. Kinetic studies showed that the mutant protein had the same affinity to serine as the wildtype protein, but a lower Vmax for serine. These results suggested that the mutation perturbs the active site of the protein, facilitating the formation of alanine condensation products. However, small increases in extracellular serine levels were able to inhibit the reaction with alanine. The palmitoyl-CoA/alanine product, 1-deoxysphinganine (1-deoxySa), was shown to increased endoplasmic reticulum stress and the unfolded protein response, which may ultimately be toxic to neurons. <a href="#17" class="mim-tip-reference" title="Gable, K., Gupta, S. D., Han, G., Niranjanakumari, S., Harmon, J. M., Dunn, T. M. <strong>A disease-causing mutation in the active site of serine palmitoyltransferase causes catalytic promiscuity.</strong> J. Biol. Chem. 285: 22846-22852, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20504773/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20504773</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20504773[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/10.1074/jbc.M110.122259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20504773">Gable et al. (2010)</a> concluded that their findings were consistent with a gain of function that is responsible for the HSAN1 phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20504773" 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>SPT catalyzes the condensation of serine and palmitoyl-CoA, the initial step in the de novo synthesis of sphingolipids. <a href="#30" class="mim-tip-reference" title="Penno, A., Reilly, M. M., Houlden, H., Laura, M., Rentsch, K., Niederkofler, V., Stoeckli, E. T., Nicholson, G., Eichler, F., Brown, R. H., Jr., von Eckardstein, A., Hornemann, T. <strong>Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids.</strong> J. Biol. Chem. 285: 11178-11187, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20097765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20097765</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20097765[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/10.1074/jbc.M109.092973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20097765">Penno et al. (2010)</a> showed that HSAN1A-related mutations in the SPTLC1 gene induced a shift in the substrate specificity of SPT, which leads to the formation of 2 atypical deoxysphingoid bases: 1-deoxysphinganine from condensation with alanine and 1-deoxymethylsphinganine from condensation with glycine. Neither of these metabolites can be converted to complex sphingolipids or degraded, resulting in their intracellular accumulation. These atypical agents showed pronounced neurotoxic effects on neurite formation in cultured sensory neurons, and was associated with disturbed neurofilament structure. <a href="#30" class="mim-tip-reference" title="Penno, A., Reilly, M. M., Houlden, H., Laura, M., Rentsch, K., Niederkofler, V., Stoeckli, E. T., Nicholson, G., Eichler, F., Brown, R. H., Jr., von Eckardstein, A., Hornemann, T. <strong>Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids.</strong> J. Biol. Chem. 285: 11178-11187, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20097765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20097765</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20097765[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/10.1074/jbc.M109.092973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20097765">Penno et al. (2010)</a> found increased levels of these atypical agents in lymphocytes and plasma of HSAN1A patients with different SPTLC1 mutations. The findings indicated that HSAN1 results from gain-of-function mutations that cause the formation of atypical and neurotoxic sphingolipid metabolites, rather than from lack of de novo sphingolipid synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20097765" 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 all affected members of 11 families with HSAN1A, <a href="#9" class="mim-tip-reference" title="Dawkins, J. L., Hulme, D. J., Brahmbhatt, S. B., Auer-Grumbach, M., Nicholson, G. A. <strong>Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I.</strong> Nature Genet. 27: 309-312, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242114</a>] [<a href="https://doi.org/10.1038/85879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11242114">Dawkins et al. (2001)</a> identified heterozygous missense mutations in the SPTLC1 gene (C133Y, <a href="/entry/605712#0001">605712.0001</a>; C133W, <a href="/entry/605712#0002">605712.0002</a>; V144D, <a href="/entry/605712#0003">605712.0003</a>). Four of the families had previously been reported by <a href="#28" class="mim-tip-reference" title="Nicholson, G. A., Dawkins, J. L., Blair, I. P., Kennerson, M. L., Gordon, M. J., Cherryson, A. K., Nash, J., Bananis, T. <strong>The gene for hereditary sensory neuropathy type I (HSN-1) maps to chromosome 9q22.1-q22.3.</strong> Nature Genet. 13: 101-104, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673084</a>] [<a href="https://doi.org/10.1038/ng0596-101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673084">Nicholson et al. (1996)</a>, including the multigenerational Australian family originally reported by <a href="#23" class="mim-tip-reference" title="Jackson, M. <strong>Familial lumbo-sacral syringomyelia and the significance of developmental errors of the spinal cord and column.</strong> Med. J. Aust. 1: 434-439, 1949."None>Jackson (1949)</a> and followed up by Wallace (<a href="#38" class="mim-tip-reference" title="Wallace, D. C. <strong>A Study of an Hereditary Neuropathy.</strong> Thesis: Univ. of Sydney (pub.) 1968."None>1968</a>, <a href="#39" class="mim-tip-reference" title="Wallace, D. C. <strong>Hereditary sensory radicular neuropathy. In: Archdall Medical Monograph 8.</strong> Sydney: Australasian Med. Pub. Co. 1970."None>1970</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11242114+8673084" 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="#2" class="mim-tip-reference" title="Bejaoui, K., Wu, C., Scheffler, M. D., Haan, G., Ashby, P., Wu, L., de Jong, P., Brown, R. H., Jr. <strong>SPTLC1 is mutated in hereditary sensory neuropathy, type 1.</strong> Nature Genet. 27: 261-262, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242106</a>] [<a href="https://doi.org/10.1038/85817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11242106">Bejaoui et al. (2001)</a> independently identified 2 of the same SPTLC1 mutations in 2 unrelated families with HSN1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242106" 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 twin sisters with HSN1 from a Belgian family originally reported by <a href="#26" class="mim-tip-reference" title="Montanini, R. <strong>Acropatia ulcero-mutilante, amiotrofia frusta tipo Charcot-Marie e alessia in due gemelle univitelline.</strong> Riv. Neurol. 28: 593-609, 1958.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13646503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13646503</a>]" pmid="13646503">Montanini (1958)</a>, <a href="#37" class="mim-tip-reference" title="Verhoeven, K., Coen, K., De Vriendt, E., Jacobs, A., Van Gerwen, V., Smouts, I., Pou-Serradell, A., Martin, J.-J., Timmerman, V., De Jonghe, P. <strong>SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I.</strong> Neurology 62: 1001-1002, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037712</a>] [<a href="https://doi.org/10.1212/01.wnl.0000115388.10828.5c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15037712">Verhoeven et al. (2004)</a> identified a mutation in the SPTLC1 gene (G387A; <a href="/entry/605712#0004">605712.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13646503+15037712" 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>The findings of <a href="#21" class="mim-tip-reference" title="Hornemann, T., Penno, A., Richard, S., Nicholson, G., van Dijk, F. S., Rotthier, A., Timmerman, V., von Eckardstein, A. <strong>A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated.</strong> Neurogenetics 10: 135-143, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19132419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19132419</a>] [<a href="https://doi.org/10.1007/s10048-008-0168-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19132419">Hornemann et al. (2009)</a> cast doubt on the pathogenicity of the G387A mutation. By in vitro functional expression assays in HEK293 cells, <a href="#21" class="mim-tip-reference" title="Hornemann, T., Penno, A., Richard, S., Nicholson, G., van Dijk, F. S., Rotthier, A., Timmerman, V., von Eckardstein, A. <strong>A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated.</strong> Neurogenetics 10: 135-143, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19132419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19132419</a>] [<a href="https://doi.org/10.1007/s10048-008-0168-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19132419">Hornemann et al. (2009)</a> found that none of the 4 SPTLC1 mutations, C133Y, C133W, V144D, or G387A, interfered with formation of the SPT complex. The first 3 mutant proteins resulted in 40 to 50% decreased SPT activity, but the G387A protein showed no effect on SPT activity. Further studies showed that the G387A protein could rescue a SPTLC1-deficient cell line. Finally, <a href="#21" class="mim-tip-reference" title="Hornemann, T., Penno, A., Richard, S., Nicholson, G., van Dijk, F. S., Rotthier, A., Timmerman, V., von Eckardstein, A. <strong>A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated.</strong> Neurogenetics 10: 135-143, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19132419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19132419</a>] [<a href="https://doi.org/10.1007/s10048-008-0168-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19132419">Hornemann et al. (2009)</a> identified an unaffected woman who was homozygous for the G387A mutation, suggesting that it is not pathogenic. <a href="#21" class="mim-tip-reference" title="Hornemann, T., Penno, A., Richard, S., Nicholson, G., van Dijk, F. S., Rotthier, A., Timmerman, V., von Eckardstein, A. <strong>A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated.</strong> Neurogenetics 10: 135-143, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19132419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19132419</a>] [<a href="https://doi.org/10.1007/s10048-008-0168-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19132419">Hornemann et al. (2009)</a> postulated that the G387A variant, and perhaps the other 3 SPTLC1 variants previously associated with HSN1, may not be directly disease-causing, but rather have an indirect or bystander effect by increasing the risk for HSN1 in conjunction with another mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19132419" 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>Three patients with a severe form of HSAN1 were heterozygous for mutations at the same codon in the SPTLC1 gene (S331F, <a href="/entry/605712#0005">605712.0005</a> and S331Y, <a href="/entry/605712#0007">605712.0007</a>) (<a href="#32" class="mim-tip-reference" title="Rotthier, A., Baets, J., De Vriendt, E., Jacobs, A., Auer-Grumbach, M., Levy, N., Bonello-Palot, N., Kilic, S. S., Weis, J., Nascimento, A., Swinkels, M., Kruyt, M. C., Jordanova, A., De Jonghe, P., Timmerman, V. <strong>Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.</strong> Brain 132: 2699-2711, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19651702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19651702</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19651702[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/brain/awp198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19651702">Rotthier et al., 2009</a>; <a href="#1" class="mim-tip-reference" title="Auer-Grumbach, M., Bode, H., Pieber, T. R., Schabhuttl, M., Fischer, D., Seidl, R., Graf, E., Wieland, T., Schuh, R., Vacariu, G., Grill, F., Timmerman, V., Strom, T. M., Hornemann, T. <strong>Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype.</strong> Europ. J. Med. Genet. 56: 266-269, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23454272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23454272</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23454272[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ejmg.2013.02.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23454272">Auer-Grumbach et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23454272+19651702" 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>Using biochemical assays in transfected cells, <a href="#5" class="mim-tip-reference" title="Bode, H., Bourquin, F., Suriyanarayanan, S., Wei, Y., Alecu, I., Othman, A., Von Eckardstein, A., Hornemann, T. <strong>HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship.</strong> Hum. Molec. Genet. 25: 853-865, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26681808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26681808</a>] [<a href="https://doi.org/10.1093/hmg/ddv611" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26681808">Bode et al. (2016)</a> assessed the enzymatic activity and biochemical consequences of 11 different missense variants in the SPTLC1 gene, including 7 that had previously been identified in HSAN1A patients. None of the variants resulted in a loss of activity, as had previously been suggested. Several variants, including V144D, A310G, A339V, and A352V, showed no change in canonical enzyme activity and did not form increased levels of neurotoxic 1-deoxySL compounds. The authors suggested that these variants are not pathogenic and may not be causative of the phenotype. Two mutations, C133Y and C133W, were associated with increased 1-deoxySL levels compared to wildtype, but had unaltered canonical activity. These mutations were associated with a typical late-onset phenotype with primarily sensory and mild motor impairment. Two mutations, S331F and S331Y, were characterized by increased canonical enzyme activity as well as increased formation of C18-, 1-deoxy-, and C20-sphingoid bases, the latter of which was a unique and particular hallmark of these mutations. These mutations were associated with a severe phenotype characterized by early onset of symptoms, autonomic impairment, and juvenile cataracts. Further studies showed that the formation of toxic 1-deoxySL in animal models and patients with HSAN1 was reduced by increased availability of serine through oral supplementation. In contrast, increased availability of alanine resulted in augmented 1-deoxySL formation and aggravated neuropathic symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26681808" 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="#27" class="mim-tip-reference" title="Nicholson, G. A., Dawkins, J. L., Blair, I. P., Auer-Grumbach, M., Brahmbhatt, S. B., Hulme, D. J. <strong>Hereditary sensory neuropathy type I: haplotype analysis shows founders in southern England and Europe.</strong> Am. J. Hum. Genet. 69: 655-659, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479835</a>] [<a href="https://doi.org/10.1086/323252" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11479835">Nicholson et al. (2001)</a> found that 3 Australian families of English extraction and 3 English families with HSAN1A had the same SPTLC1 mutation (<a href="/entry/605712#0002">605712.0002</a>), the same chromosome 9 haplotype, and the same phenotype. They therefore concluded that the Australian and English families had the same founder who, on the basis of historical information, lived in southern England before 1800. The phenotype caused by this mutation is the same as that in the English families of <a href="#6" class="mim-tip-reference" title="Campbell, A. M. G., Hoffman, H. L. <strong>Sensory radicular neuropathy associated with muscle wasting in two cases.</strong> Brain 87: 67-74, 1964.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14152213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14152213</a>] [<a href="https://doi.org/10.1093/brain/87.1.67" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14152213">Campbell and Hoffman (1964)</a> and possibly in the original English family of <a href="#20" class="mim-tip-reference" title="Hicks, E. P. <strong>Hereditary perforating ulcer of the foot.</strong> Lancet 199: 319-321, 1922. Note: Originally Volume I."None>Hicks (1922)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11479835+14152213" 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="#Clarke1909" class="mim-tip-reference" title="Clarke, J. M., Groves, E. W. H. <strong>Remarks on syringomyelia (sacro-lumbar type) occurring in a brother and sister.</strong> Brit. Med. J. 2: 737-740, 1909.">Clarke and Groves (1909)</a>; <a href="#Danon1985" class="mim-tip-reference" title="Danon, M. J., Carpenter, S. <strong>Hereditary sensory neuropathy: biopsy study of an autosomal dominant variety.</strong> Neurology 35: 1226-1229, 1985.">Danon and Carpenter (1985)</a>; <a href="#Miller1976" class="mim-tip-reference" title="Miller, R. G., Nielsen, S. L., Sumner, A. J. <strong>Hereditary sensory neuropathy and tonic pupils.</strong> Neurology 26: 931-935, 1976.">Miller et al.
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(1976)</a>; <a href="#Ogryzlo1946" class="mim-tip-reference" title="Ogryzlo, M. A. <strong>A familial peripheral neuropathy of unknown etiology resembling Morvan's disease.</strong> Canad. Med. Assoc. J. 54: 547-553, 1946.">Ogryzlo (1946)</a>; <a href="#Schultze1917" class="mim-tip-reference" title="Schultze, F. <strong>Familiaer auftretendes malum perforans der Fuesse (familiaere lumbale Syringomyelie).</strong> Dtsch. Med. Wschr. 43: 545-547, 1917.">Schultze (1917)</a>; <a href="#Smith1934" class="mim-tip-reference" title="Smith, E. M. <strong>Familial neurotrophic osseous atrophy: a familial neurotrophic condition of the feet with anesthesia and loss of bone.</strong> JAMA 102: 593-595, 1934.">Smith (1934)</a>; <a href="#Tocantins1939" class="mim-tip-reference" title="Tocantins, L. M., Reimann, H. A. <strong>Perforating ulcers of feet, with osseous atrophy in family with other evidences of dysgenesis (hare lip, cleft palate): an instance of probable myelodysplasia.</strong> JAMA 112: 2251-2255, 1939.">Tocantins and
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Reimann (1939)</a>
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Auer-Grumbach, M., Bode, H., Pieber, T. R., Schabhuttl, M., Fischer, D., Seidl, R., Graf, E., Wieland, T., Schuh, R., Vacariu, G., Grill, F., Timmerman, V., Strom, T. M., Hornemann, T.
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<strong>Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype.</strong>
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Europ. J. Med. Genet. 56: 266-269, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23454272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23454272</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23454272[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=23454272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ejmg.2013.02.002" target="_blank">Full Text</a>]
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Bejaoui, K., Wu, C., Scheffler, M. D., Haan, G., Ashby, P., Wu, L., de Jong, P., Brown, R. H., Jr.
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<strong>SPTLC1 is mutated in hereditary sensory neuropathy, type 1.</strong>
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Nature Genet. 27: 261-262, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242106</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242106" 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/10.1038/85817" target="_blank">Full Text</a>]
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Blair, I. P., Dawkins, J. L., Nicholson, G. A.
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<strong>Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q21.1-q22.3: exclusion of GAS1 and XPA.</strong>
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Cytogenet. Cell Genet. 78: 140-141, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9371409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9371409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9371409" 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/10.1159/000134649" target="_blank">Full Text</a>]
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Blair, I. P., Hulme, D., Dawkins, J. L., Nicholson, G. A.
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<strong>A YAC-based transcript map of human chromosome 9q22.1-q22.3 encompassing the loci for hereditary sensory neuropathy type I and multiple self-healing squamous epithelioma.</strong>
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Genomics 51: 277-281, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9722951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9722951</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9722951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1998.5373" target="_blank">Full Text</a>]
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Bode, H., Bourquin, F., Suriyanarayanan, S., Wei, Y., Alecu, I., Othman, A., Von Eckardstein, A., Hornemann, T.
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<strong>HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship.</strong>
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Hum. Molec. Genet. 25: 853-865, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26681808/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26681808</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26681808" 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/ddv611" target="_blank">Full Text</a>]
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Campbell, A. M. G., Hoffman, H. L.
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<strong>Sensory radicular neuropathy associated with muscle wasting in two cases.</strong>
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Brain 87: 67-74, 1964.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14152213/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14152213</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14152213" 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/brain/87.1.67" target="_blank">Full Text</a>]
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Clarke, J. M., Groves, E. W. H.
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<strong>Remarks on syringomyelia (sacro-lumbar type) occurring in a brother and sister.</strong>
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Brit. Med. J. 2: 737-740, 1909.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20764666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20764666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20764666" 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/10.1136/bmj.2.2542.737" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/wnl.35.8.1226" target="_blank">Full Text</a>]
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<strong>Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I.</strong>
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[<a href="https://doi.org/10.1038/85879" target="_blank">Full Text</a>]
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<strong>Progressive ventral sensory loss in sensory radicular neuropathy and hypertrophic neuritis.</strong>
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[<a href="https://doi.org/10.1136/jnnp.14.4.237" target="_blank">Full Text</a>]
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<strong>Phenotypic and genetic study of a family with hereditary sensory neuropathy and prominent weakness.</strong>
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[<a href="https://doi.org/10.1002/1097-4598(200010)23:10<1508::aid-mus6>3.0.co;2-d" target="_blank">Full Text</a>]
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<strong>A Virginia kinship with hereditary sensory neuropathy: peroneal muscular atrophy and pes cavus.</strong>
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<strong>Randomized trial of I-serine in patients with hereditary sensory and autonomic neuropathy type 1.</strong>
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[<a href="https://doi.org/10.1212/WNL.0000000000006811" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.M110.122259" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJMoa1815111" target="_blank">Full Text</a>]
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<strong>Is there involvement of the central nervous system in hereditary sensory radicular neuropathy?</strong>
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[<a href="https://doi.org/10.1016/0303-8467(92)90119-n" target="_blank">Full Text</a>]
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<strong>Hereditary perforating ulcer of the foot.</strong>
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Lancet 199: 319-321, 1922. Note: Originally Volume I.
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<strong>A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19132419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19132419</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19132419" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10048-008-0168-7" target="_blank">Full Text</a>]
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<a id="Huehne2008" class="mim-anchor"></a>
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<strong>Novel missense, insertion and deletion mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with congenital insensitivity to pain with anhidrosis.</strong>
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[<a href="https://doi.org/10.1016/j.nmd.2007.10.005" target="_blank">Full Text</a>]
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<strong>Hereditary sensory radicular neuropathy.</strong>
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[<a href="https://doi.org/10.1212/wnl.10.7.627" target="_blank">Full Text</a>]
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<strong>Hereditary sensory neuropathy and tonic pupils.</strong>
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[<a href="https://doi.org/10.1212/wnl.26.10.931" target="_blank">Full Text</a>]
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<a id="26" class="mim-anchor"></a>
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<a id="Montanini1958" class="mim-anchor"></a>
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Montanini, R.
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<strong>Acropatia ulcero-mutilante, amiotrofia frusta tipo Charcot-Marie e alessia in due gemelle univitelline.</strong>
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Riv. Neurol. 28: 593-609, 1958.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13646503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13646503</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13646503" 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="Nicholson2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nicholson, G. A., Dawkins, J. L., Blair, I. P., Auer-Grumbach, M., Brahmbhatt, S. B., Hulme, D. J.
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<strong>Hereditary sensory neuropathy type I: haplotype analysis shows founders in southern England and Europe.</strong>
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Am. J. Hum. Genet. 69: 655-659, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11479835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11479835</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11479835" 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/10.1086/323252" target="_blank">Full Text</a>]
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<a id="28" class="mim-anchor"></a>
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<a id="Nicholson1996" class="mim-anchor"></a>
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<div class="">
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Nicholson, G. A., Dawkins, J. L., Blair, I. P., Kennerson, M. L., Gordon, M. J., Cherryson, A. K., Nash, J., Bananis, T.
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<strong>The gene for hereditary sensory neuropathy type I (HSN-1) maps to chromosome 9q22.1-q22.3.</strong>
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Nature Genet. 13: 101-104, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673084</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673084" 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/ng0596-101" target="_blank">Full Text</a>]
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<a id="29" class="mim-anchor"></a>
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<a id="Ogryzlo1946" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ogryzlo, M. A.
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<strong>A familial peripheral neuropathy of unknown etiology resembling Morvan's disease.</strong>
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Canad. Med. Assoc. J. 54: 547-553, 1946.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20983620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20983620</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20983620" 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="Penno2010" class="mim-anchor"></a>
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Penno, A., Reilly, M. M., Houlden, H., Laura, M., Rentsch, K., Niederkofler, V., Stoeckli, E. T., Nicholson, G., Eichler, F., Brown, R. H., Jr., von Eckardstein, A., Hornemann, T.
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<strong>Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids.</strong>
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J. Biol. Chem. 285: 11178-11187, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20097765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20097765</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20097765[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=20097765" 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/10.1074/jbc.M109.092973" target="_blank">Full Text</a>]
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<a id="Rotthier2010" class="mim-anchor"></a>
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<div class="">
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Rotthier, A., Auer-Grumbach, M., Janssens, K., Baets, J., Penno, A., Almeida-Souza, L., Van Hoof, K., Jacobs, A., De Vriendt, E., Schlotter-Weigel, B., Loscher, W., Vondracek, P., Seeman, P., De Jonghe, P., Van Dijck, P., Jordanova, A., Hornemann, T., Timmerman, V.
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<strong>Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I.</strong>
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Am. J. Hum. Genet. 87: 513-522, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20920666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20920666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20920666[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=20920666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2010.09.010" target="_blank">Full Text</a>]
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<a id="Rotthier2009" class="mim-anchor"></a>
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Rotthier, A., Baets, J., De Vriendt, E., Jacobs, A., Auer-Grumbach, M., Levy, N., Bonello-Palot, N., Kilic, S. S., Weis, J., Nascimento, A., Swinkels, M., Kruyt, M. C., Jordanova, A., De Jonghe, P., Timmerman, V.
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<strong>Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.</strong>
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Brain 132: 2699-2711, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19651702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19651702</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19651702[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=19651702" 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/brain/awp198" target="_blank">Full Text</a>]
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<a id="Schultze1917" class="mim-anchor"></a>
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<div class="">
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Schultze, F.
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<strong>Familiaer auftretendes malum perforans der Fuesse (familiaere lumbale Syringomyelie).</strong>
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Dtsch. Med. Wschr. 43: 545-547, 1917.
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<a id="Silverman1959" class="mim-anchor"></a>
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<p class="mim-text-font">
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Silverman, F. N., Gilden, J. J.
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<strong>Congenital insensitivity to pain, a neurologic syndrome with bizarre skeletal lesions.</strong>
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Radiology 72: 176-190, 1959.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13634374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13634374</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13634374" 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/10.1148/72.2.176" target="_blank">Full Text</a>]
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<a id="Smith1934" class="mim-anchor"></a>
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<div class="">
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Smith, E. M.
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<strong>Familial neurotrophic osseous atrophy: a familial neurotrophic condition of the feet with anesthesia and loss of bone.</strong>
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JAMA 102: 593-595, 1934.
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<a id="Tocantins1939" class="mim-anchor"></a>
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<div class="">
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Tocantins, L. M., Reimann, H. A.
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<strong>Perforating ulcers of feet, with osseous atrophy in family with other evidences of dysgenesis (hare lip, cleft palate): an instance of probable myelodysplasia.</strong>
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JAMA 112: 2251-2255, 1939.
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Verhoeven, K., Coen, K., De Vriendt, E., Jacobs, A., Van Gerwen, V., Smouts, I., Pou-Serradell, A., Martin, J.-J., Timmerman, V., De Jonghe, P.
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<strong>SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I.</strong>
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Neurology 62: 1001-1002, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15037712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15037712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15037712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000115388.10828.5c" target="_blank">Full Text</a>]
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Wallace, D. C.
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<strong>A Study of an Hereditary Neuropathy.</strong>
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Thesis: Univ. of Sydney (pub.) 1968.
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Wallace, D. C.
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<strong>Hereditary sensory radicular neuropathy. In: Archdall Medical Monograph 8.</strong>
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Sydney: Australasian Med. Pub. Co. 1970.
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 11/04/2019
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<span class="mim-text-font">
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Carol A. Bocchini - updated : 10/22/2019<br>Cassandra L. Kniffin - updated : 11/12/2010<br>Cassandra L. Kniffin - updated : 9/23/2010<br>Cassandra L. Kniffin - updated : 5/14/2009<br>Cassandra L. Kniffin - updated : 2/6/2009<br>Cassandra L. Kniffin - updated : 9/1/2005<br>Cassandra L. Kniffin - updated : 5/18/2004<br>Denise L. M. Goh - updated : 4/10/2003<br>Carol A. Bocchini - reorganized : 10/5/2001<br>Victor A. McKusick - updated : 9/27/2001<br>Ada Hamosh - updated : 3/2/2001<br>Sheryl A. Jankowski - updated : 12/22/1998<br>Victor A. McKusick - updated : 12/2/1997
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Victor A. McKusick : 6/2/1986
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carol : 04/02/2021
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carol : 11/23/2020<br>carol : 11/04/2019<br>ckniffin : 11/04/2019<br>carol : 10/28/2019<br>carol : 10/25/2019<br>carol : 10/23/2019<br>carol : 10/22/2019<br>carol : 07/12/2017<br>carol : 07/11/2017<br>carol : 10/13/2016<br>carol : 05/13/2016<br>alopez : 7/29/2015<br>ckniffin : 7/28/2015<br>carol : 11/19/2014<br>carol : 11/10/2014<br>ckniffin : 10/28/2014<br>ckniffin : 2/10/2014<br>carol : 12/4/2013<br>ckniffin : 12/3/2013<br>alopez : 5/29/2012<br>ckniffin : 5/29/2012<br>carol : 9/16/2011<br>ckniffin : 9/15/2011<br>alopez : 7/29/2011<br>ckniffin : 7/27/2011<br>wwang : 2/23/2011<br>ckniffin : 1/28/2011<br>carol : 11/16/2010<br>ckniffin : 11/12/2010<br>wwang : 10/6/2010<br>ckniffin : 9/23/2010<br>terry : 12/16/2009<br>terry : 6/3/2009<br>wwang : 5/27/2009<br>ckniffin : 5/14/2009<br>wwang : 2/6/2009<br>terry : 2/3/2009<br>carol : 7/12/2007<br>wwang : 9/6/2005<br>ckniffin : 9/1/2005<br>ckniffin : 8/17/2005<br>tkritzer : 9/8/2004<br>ckniffin : 8/27/2004<br>alopez : 8/17/2004<br>terry : 7/27/2004<br>tkritzer : 6/11/2004<br>carol : 5/21/2004<br>ckniffin : 5/18/2004<br>ckniffin : 5/18/2004<br>cwells : 11/5/2003<br>carol : 4/29/2003<br>carol : 4/10/2003<br>carol : 10/5/2001<br>carol : 10/5/2001<br>mcapotos : 10/4/2001<br>terry : 9/27/2001<br>alopez : 3/2/2001<br>terry : 3/2/2001<br>carol : 10/22/1999<br>psherman : 1/6/1999<br>psherman : 12/22/1998<br>carol : 7/8/1998<br>carol : 5/20/1998<br>mark : 12/10/1997<br>terry : 12/2/1997<br>randy : 8/31/1996<br>terry : 5/14/1996<br>terry : 5/6/1996<br>mimadm : 12/2/1994<br>terry : 7/15/1994<br>warfield : 4/21/1994<br>carol : 10/26/1993<br>carol : 8/31/1993<br>supermim : 3/16/1992
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<strong>#</strong> 162400
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NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IA; HSAN1A
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<em>Alternative titles; symbols</em>
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HSAN IA<br />
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HSAN1<br />
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NEUROPATHY, HEREDITARY SENSORY, TYPE IA; HSN1A<br />
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HSN IA<br />
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NEUROPATHY, HEREDITARY SENSORY RADICULAR, AUTOSOMAL DOMINANT, TYPE 1A
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<strong>SNOMEDCT:</strong> 230553002, 397734008, 860813007;
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<strong>ORPHA:</strong> 36386;
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<strong>DO:</strong> 0070152;
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<strong>Phenotype-Gene Relationships</strong>
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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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9q22.31
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Neuropathy, hereditary sensory and autonomic, type IA
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162400
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Autosomal dominant
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<span class="mim-font">
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3
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SPTLC1
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605712
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because hereditary sensory neuropathy type IA (HSAN1A) is caused by heterozygous mutation in the SPTLC1 gene (605712) on chromosome 9q22.</p>
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<strong>Description</strong>
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<p>Hereditary sensory and autonomic neuropathy type IA (HSAN1A) is an autosomal dominant neurologic disorder characterized by sensory neuropathy with variable autonomic and motor involvement. Most patients have adult onset of slowly progressive distal sensory impairment manifest as numbness, tingling, or pain, as well as distal muscle atrophy. Complications include ulceration and osteomyelitis. Some patients may have a more severe phenotype with onset in childhood. Electrophysiologic studies show a predominantly axonal neuropathy with some demyelinating features. Some patients may have evidence of central nervous system involvement, including macular telangiectasia type 2. Affected individuals have increased levels of plasma 1-deoxysphingolipids (1-deoxySLs), which are thought to be neurotoxic (summary by Rotthier et al., 2010 and Gantner et al., 2019). Oral supplementation with serine decreases 1-deoxySL and may offer some clinical benefits (Fridman et al., 2019). </p><p><strong><em>Genetic Heterogeneity of Hereditary Sensory and Autonomic Neuropathy</em></strong></p><p>
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See also HSAN1C (613640), caused by mutation in the SPTLC2 gene (605713) on 14q24; HSN1D (613708), caused by mutation in the ATL1 gene (606439) on 14q22; HSN1E (614116), caused by mutation in the DNMT1 gene (126375) on 19p13; HSN1F (615632), caused by mutation in the ATL3 gene (609369) on 11q13; HSAN2A (201300), caused by mutation in the HSN2 isoform of the WNK1 gene (605232) on 12p13; HSAN2B (613115), caused by mutation in the FAM134B gene (613114) on 5p15; HSN2C (614213), caused by mutation in the KIF1A gene (601255) on 2q37; HSAN2D (see 243000), caused by mutation in the SCN9A gene (603415) on 2q24; HSAN3 (223900), caused by mutation in the ELP1 gene (603722) on 9q31; HSAN4 (256800), caused by mutation in the NTRK1 gene (191315) on 1q23; HSAN5 (608654), caused by mutation in the NGF gene (162030) on 1p13; HSAN6 (614653), caused by mutation in the DST gene (113810) on 6p12; HSAN7 (615548), caused by mutation in the SCN11A gene (604385) on 3p22; and HSAN8 (616488), caused by mutation in the PRDM12 gene (616458) on chromosome 9q34.</p><p>Adult-onset HSAN with anosmia (608720) may be another distinct form of HSAN, and HSAN1B (608088) with cough and gastroesophageal reflux maps to chromosome 3p24-p22.</p>
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<strong>Clinical Features</strong>
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<p>Hicks (1922) described an English family in which 10 members suffered from perforating ulcers of the feet, shooting pains, and deafness. Age of onset ranged from 15 to 36 years. Presentation was usually with a corn on a big toe followed by a painless ulcer with bony debris. Patients later experienced shooting pains similar to the lightning pains of tabes dorsalis and developed bilateral deafness progressing to total deafness over several years. Neurologic examination showed disappearance of ankle and knee jerks and absence of an extensor plantar response. There was loss of pain, touch, heat, and cold sensation over the feet, but sensation of the arms remained normal. Cranial nerves were normal, with the exception of the auditory nerve, pupils reacted normally, and there was no nystagmus. Hicks (1922) noted that although hereditary perforating ulcers of the feet had been reported in patients in the past, there had been no previous mention of accompanying deafness or shooting pains. Denny-Brown (1951) reported the clinical and autopsy findings of a 53-year-old woman who was a member of the family reported by Hicks (1922). When she was 22 years of age, an ulcer formed on her right great toe, requiring a year to heal. She subsequently suffered from recurrent ulceration, each episode lasting 6 to 9 months and sometimes extending to bone. In her early twenties, she first noticed shooting pains in her legs, sometimes in her arms. Deafness began at the age of 40 years and progressed to almost total deafness by 53 years of age. Neurologic examination at 53 years of age showed loss of all sensation in the lower legs, with loss of pain and temperature sensation in the thighs and hands. Autopsy showed a small brain and marked loss of ganglion cells in the sacral and lumbar dorsal root ganglia. Remaining ganglion cells showed proliferation of subcapsular dendrites and hyaline bodies, possibly representing an amyloid mass around capillaries. There were less severe changes in C-8 and T-1 ganglia. The affected families reported by Ervin and Sternbach (1960) and Silverman and Gilden (1959) appeared to show autosomal dominant inheritance. Mandell and Smith (1960) observed sensory radicular neuropathy in 3 generations of a family. Clinical features included neuropathic arthropathy, recurrent ulceration of the lower extremities, and signs of radicular sensory deficiency in both the upper and the lower extremities without any motor dysfunction. Dyck et al. (1965) described a family with sensory neuropathy accompanied by peroneal muscular atrophy and pes cavus. Campbell and Hoffman (1964) and DeLeon (1969) also reported cases in which amyotrophy was a feature. Using a cholinesterase technique on skin biopsies from the pad of the great toe of affected persons, Dyck et al. (1965) found normal numbers of Meissner corpuscles in a 14-year-old boy with early signs suggestive of the disorder, but no corpuscles in a 37-year-old man and a 28-year-old woman with well-developed disease. </p><p>Dyck et al. (1983) noted that 'burning feet' may be the only manifestation of dominantly inherited sensory neuropathy. The symptoms are ameliorated by cold and aggravated by heat. Restless legs and lancinating pain are other presentations of the disorder, which often resulted in severe distal sensory loss, mutilating acropathy, and neurotrophic arthropathy. </p><p>In a detailed clinical study of a patient with HSN1, including audiometric testing, autonomic functions, electromyography, transcranial magnetic stimulation, and brain imaging, Hageman et al. (1992) determined that there were no signs of central nervous system involvement and stated that HSN1 is a disorder of the dorsal root ganglia and peripheral nerves. </p><p>Wallace (1968, 1970) studied an extensively affected Australian kindred. In a study of this kindred and 3 other Australian kindreds with HSAN1, Nicholson et al. (1996) found that a typical history included lightning pains, painless skin injuries and ulceration, and signs including distal sensory loss to sharp, hot, and cold sensation, with loss of distal reflexes and distal muscle wasting. Nerve conduction velocities showed an axonal neuropathy, particularly of the lower limbs. </p><p>Dubourg et al. (2000) reported a French family with autosomal dominant hereditary sensory neuropathy suggestive of linkage to chromosome 9q. Mean age at onset was 34 years. All patients presented with distal sensory loss and distal muscle weakness of both the upper and lower limbs. Four patients had foot ulcerations, and 3 patients had hyperhidrosis. Motor nerve conduction velocities were normal or mildly decreased, consistent with an axonal neuropathy. Sensory nerve action potentials were either reduced or could not be recorded. </p><p><strong><em>Severe Phenotype</em></strong></p><p>
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Rotthier et al. (2009) reported a French Gypsy patient with an unusually severe form of HSAN1. The patient had congenital insensitivity to pain with eschar and foot ulceration, pes cavus/equinovarus, vocal cord paralysis, and gastroesophageal reflux. The patient also had severe growth and mental retardation, microcephaly, hypotonia, amyotrophy, and respiratory insufficiency. Nerve conduction studies showed absent sensory and motor responses in the upper and lower limbs. Genetic analysis identified a de novo heterozygous mutation in the SPTLC1 gene (S331F; 605712.0005). The phenotype expanded the clinical spectrum of HSAN1. </p><p>Auer-Grumbach et al. (2013) reported that a patient (ER-CIPA-20374) described by Huehne et al. (2008) with a severe form of HSAN1 had the same heterozygous S331F mutation in the SPTLC1 gene as that reported by Rotthier et al. (2009) in a patient with early-onset severe HSAN1A. The patient described by Huehne et al. (2008) and Auer-Grumbach et al. (2013) had onset in early childhood or muscle weakness and hypotrophy in addition to prominent sensory disturbances, bone fractures, and osteomyelitis. The patient developed cataract at age 9 years, complete retinal detachment at age 10, and repetitive corneal ulceration and keratitis with poor wound healing. </p><p>In another patient with a severe form of HSAN1, Auer-Grumbach et al. (2013) identified a different de novo heterozygous mutation at the same codon (S331Y; 605712.0007). This patient had onset at age 4 years of unsteady gait, hand tremor, mild sensory disturbances, and a pes cavus foot deformity necessitating triple arthrodesis at age 5. At examination at age 12, there was general muscle hypotrophy and hypotonia with pronounced weakness in the distal muscles of the upper and lower limbs. There were prominent sensory disturbances; these were pronounced in the feet and affected all qualities except for the vibration sense, which remained completely preserved. At the toes, scars from burns due to reduced pain and temperature sensation were evident. There was also hypermobility of the joints, bilateral hand tremor, and fasciculations, most prominent in the tongue. At age 13, she developed bilateral cataracts. Disease progression was rapid and led to severe scoliosis, respiratory problems, and wheelchair dependence at age 14. The patient had prominent growth retardation but normal intellectual development. The level of 1-deoxySL was significantly elevated in the patient's plasma. </p><p><strong><em>Association with Macular Telangiectasia Type 2</em></strong></p><p>
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Gantner et al. (2019) identified 9 patients, including 8 patients from 2 unrelated families and an additional unrelated patient, with genetically confirmed HSAN1A who also had type 2 macular telangiectasia. All carried the same heterozygous C133Y mutation in the SPTLC1 gene (605712.0001). The proband in the first family presented with bilateral bull's eye maculopathy at 21 years of age. Detailed ophthalmologic examination showed findings diagnostic for macular telangiectasia type 2, including parafoveal telangiectatic retinal vessels, 'right angle' venules, retinal opacification, pigment clumping, low levels of macular carotenoid pigment, leakage on fluorescein angiography, blue light-reflectance abnormalities, and intraretinal cysts and ellipsoid zone defects on optical coherence tomography (OCT). His father and sister had similar ocular findings, although the features in the sister were milder. None of these patients had received serine supplementation. All 3 patients had also been diagnosed clinically with a peripheral neuropathy, although details of the neuropathy were not provided. After exome sequencing identified the SPTLC1 mutation in this family, Gantner et al. (2019) examined additional patients with HSAN1 for macular telangiectasia. Five patients from family 2 and an unrelated woman (patient 1), all of whom also carried the C133Y SPTLC1 mutation, were similarly affected. The individuals from family 2 and patient 1 had received serine supplementation. Two additional unrelated patients (patients 2 and 3), who had HSAN1A due to a heterozygous C133W mutation in the SPTLC1 gene (605712.0002), did not have macular telangiectasia. However, both patients were under the age of 50 and had been treated with serine supplementation. Two patients from another family (family 3) with HSAN1C (613610) due to a heterozygous S384F missense mutation in the SPTLC2 gene (605713.0005) also had macular telangiectasia; they had not received serine supplementation. Gantner et al. (2019) noted that the macular phenotype in patients with HSAN1A and HSAN1C was typical of that observed in those with isolated macular telangiectasia. Moreover, previous studies (see, e.g., Penno et al., 2010, Rotthier et al., 2010, Bode et al., 2016) had demonstrated that mutations in these genes result in abnormal accumulation of neurotoxic deoxysphingolipids. There was a dose-response effect. Studies in mouse models and in cell-based retinal organoids demonstrated that low serine levels were associated with increased deoxysphingolipids that were toxic to photoreceptor cells in the retina and caused peripheral sensory deficits; the main neurotoxic species was identified as deoxydihydroceramide. Overall, the findings provided a link between altered serine and lipid metabolism, whether caused by an identified genetic defect or unknown factors, and peripheral neuropathy as well as macular telangiectasia type 2. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of HSAN1A in the families reported by Dawkins et al. (2001) was consistent with autosomal dominant inheritance. </p>
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<strong>Mapping</strong>
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<p>Nicholson et al. (1996) undertook a genomewide linkage screen in 4 Australian kindreds with hereditary sensory neuropathy, including 1 family that had been reported by Jackson (1949) and followed up by Wallace (1968, 1970). Nicholson et al. (1996) found that the disease locus, which they symbolized HSN1, mapped to an 8-cM region flanked by D9S318 and D9S176 on 9q22.1-q22.3. Multipoint linkage analysis suggested a most likely location at D9S287, within a 4.9-cM confidence interval. </p><p>Blair et al. (1997) refined the mapping of HSN1 to a 3- to 4-cM interval within the 9q22.1-q22.3 region, and excluded GAS1 (139185) and XPA (611153) as candidate genes. Using composite mapping data, Blair et al. (1998) estimated the HSN1 critical region, flanked by D9S1781 and FB19B7, at 3 to 4 Mb. </p>
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<strong>Pathogenesis</strong>
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<p>In studies of Chinese hamster ovary (CHO) cells and yeast, Gable et al. (2010) demonstrated that the mutant SPTLC1 C133W protein (605712.0002) provided sufficient SPT activity to support growth, although total enzyme activity was only 10 to 20% of wildtype. Yeast and CHO cells expressing the C133W mutant along with SPTLC2 (605713) and SSSPTA (613540) or SSSPTB (610412) showed a preferential condensation of palmitoyl-CoA to alanine rather than serine. These results were not found with wildtype SPTLC1. Kinetic studies showed that the mutant protein had the same affinity to serine as the wildtype protein, but a lower Vmax for serine. These results suggested that the mutation perturbs the active site of the protein, facilitating the formation of alanine condensation products. However, small increases in extracellular serine levels were able to inhibit the reaction with alanine. The palmitoyl-CoA/alanine product, 1-deoxysphinganine (1-deoxySa), was shown to increased endoplasmic reticulum stress and the unfolded protein response, which may ultimately be toxic to neurons. Gable et al. (2010) concluded that their findings were consistent with a gain of function that is responsible for the HSAN1 phenotype. </p><p>SPT catalyzes the condensation of serine and palmitoyl-CoA, the initial step in the de novo synthesis of sphingolipids. Penno et al. (2010) showed that HSAN1A-related mutations in the SPTLC1 gene induced a shift in the substrate specificity of SPT, which leads to the formation of 2 atypical deoxysphingoid bases: 1-deoxysphinganine from condensation with alanine and 1-deoxymethylsphinganine from condensation with glycine. Neither of these metabolites can be converted to complex sphingolipids or degraded, resulting in their intracellular accumulation. These atypical agents showed pronounced neurotoxic effects on neurite formation in cultured sensory neurons, and was associated with disturbed neurofilament structure. Penno et al. (2010) found increased levels of these atypical agents in lymphocytes and plasma of HSAN1A patients with different SPTLC1 mutations. The findings indicated that HSAN1 results from gain-of-function mutations that cause the formation of atypical and neurotoxic sphingolipid metabolites, rather than from lack of de novo sphingolipid synthesis. </p>
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<strong>Molecular Genetics</strong>
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<p>In all affected members of 11 families with HSAN1A, Dawkins et al. (2001) identified heterozygous missense mutations in the SPTLC1 gene (C133Y, 605712.0001; C133W, 605712.0002; V144D, 605712.0003). Four of the families had previously been reported by Nicholson et al. (1996), including the multigenerational Australian family originally reported by Jackson (1949) and followed up by Wallace (1968, 1970). </p><p>Bejaoui et al. (2001) independently identified 2 of the same SPTLC1 mutations in 2 unrelated families with HSN1. </p><p>In twin sisters with HSN1 from a Belgian family originally reported by Montanini (1958), Verhoeven et al. (2004) identified a mutation in the SPTLC1 gene (G387A; 605712.0004). </p><p>The findings of Hornemann et al. (2009) cast doubt on the pathogenicity of the G387A mutation. By in vitro functional expression assays in HEK293 cells, Hornemann et al. (2009) found that none of the 4 SPTLC1 mutations, C133Y, C133W, V144D, or G387A, interfered with formation of the SPT complex. The first 3 mutant proteins resulted in 40 to 50% decreased SPT activity, but the G387A protein showed no effect on SPT activity. Further studies showed that the G387A protein could rescue a SPTLC1-deficient cell line. Finally, Hornemann et al. (2009) identified an unaffected woman who was homozygous for the G387A mutation, suggesting that it is not pathogenic. Hornemann et al. (2009) postulated that the G387A variant, and perhaps the other 3 SPTLC1 variants previously associated with HSN1, may not be directly disease-causing, but rather have an indirect or bystander effect by increasing the risk for HSN1 in conjunction with another mutation. </p><p>Three patients with a severe form of HSAN1 were heterozygous for mutations at the same codon in the SPTLC1 gene (S331F, 605712.0005 and S331Y, 605712.0007) (Rotthier et al., 2009; Auer-Grumbach et al., 2013). </p>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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<span class="mim-text-font">
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<p>Using biochemical assays in transfected cells, Bode et al. (2016) assessed the enzymatic activity and biochemical consequences of 11 different missense variants in the SPTLC1 gene, including 7 that had previously been identified in HSAN1A patients. None of the variants resulted in a loss of activity, as had previously been suggested. Several variants, including V144D, A310G, A339V, and A352V, showed no change in canonical enzyme activity and did not form increased levels of neurotoxic 1-deoxySL compounds. The authors suggested that these variants are not pathogenic and may not be causative of the phenotype. Two mutations, C133Y and C133W, were associated with increased 1-deoxySL levels compared to wildtype, but had unaltered canonical activity. These mutations were associated with a typical late-onset phenotype with primarily sensory and mild motor impairment. Two mutations, S331F and S331Y, were characterized by increased canonical enzyme activity as well as increased formation of C18-, 1-deoxy-, and C20-sphingoid bases, the latter of which was a unique and particular hallmark of these mutations. These mutations were associated with a severe phenotype characterized by early onset of symptoms, autonomic impairment, and juvenile cataracts. Further studies showed that the formation of toxic 1-deoxySL in animal models and patients with HSAN1 was reduced by increased availability of serine through oral supplementation. In contrast, increased availability of alanine resulted in augmented 1-deoxySL formation and aggravated neuropathic symptoms. </p>
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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>Nicholson et al. (2001) found that 3 Australian families of English extraction and 3 English families with HSAN1A had the same SPTLC1 mutation (605712.0002), the same chromosome 9 haplotype, and the same phenotype. They therefore concluded that the Australian and English families had the same founder who, on the basis of historical information, lived in southern England before 1800. The phenotype caused by this mutation is the same as that in the English families of Campbell and Hoffman (1964) and possibly in the original English family of Hicks (1922). </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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Clarke and Groves (1909); Danon and Carpenter (1985); Miller et al.
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(1976); Ogryzlo (1946); Schultze (1917); Smith (1934); Tocantins and
|
|
Reimann (1939)
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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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<strong>Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype.</strong>
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Europ. J. Med. Genet. 56: 266-269, 2013.
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<strong>A Virginia kinship with hereditary sensory neuropathy: peroneal muscular atrophy and pes cavus.</strong>
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Dyck, P. J., Low, P. A., Stevens, J. C.
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Mayo Clin. Proc. 58: 426-429, 1983.
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Fridman, V., Suriyanarayanan, S., Novak, P., David, W., Macklin, E. A., McKenna-Yasek, D., Walsh, K., Aziz-Bose, R., Oaklander, A. L., Brown, R., Hornemann, T., Eichler, F.
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<strong>Randomized trial of I-serine in patients with hereditary sensory and autonomic neuropathy type 1.</strong>
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Neurology 10: 627-630, 1960.
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Miller, R. G., Nielsen, S. L., Sumner, A. J.
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<strong>Hereditary sensory neuropathy and tonic pupils.</strong>
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Neurology 26: 931-935, 1976.
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<p class="mim-text-font">
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Montanini, R.
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Riv. Neurol. 28: 593-609, 1958.
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<p class="mim-text-font">
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Nicholson, G. A., Dawkins, J. L., Blair, I. P., Auer-Grumbach, M., Brahmbhatt, S. B., Hulme, D. J.
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<strong>Hereditary sensory neuropathy type I: haplotype analysis shows founders in southern England and Europe.</strong>
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[PubMed: 11479835]
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<p class="mim-text-font">
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Nicholson, G. A., Dawkins, J. L., Blair, I. P., Kennerson, M. L., Gordon, M. J., Cherryson, A. K., Nash, J., Bananis, T.
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<strong>The gene for hereditary sensory neuropathy type I (HSN-1) maps to chromosome 9q22.1-q22.3.</strong>
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Ogryzlo, M. A.
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<strong>A familial peripheral neuropathy of unknown etiology resembling Morvan's disease.</strong>
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Canad. Med. Assoc. J. 54: 547-553, 1946.
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[PubMed: 20983620]
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<p class="mim-text-font">
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Penno, A., Reilly, M. M., Houlden, H., Laura, M., Rentsch, K., Niederkofler, V., Stoeckli, E. T., Nicholson, G., Eichler, F., Brown, R. H., Jr., von Eckardstein, A., Hornemann, T.
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<strong>Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids.</strong>
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[PubMed: 20097765]
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Rotthier, A., Auer-Grumbach, M., Janssens, K., Baets, J., Penno, A., Almeida-Souza, L., Van Hoof, K., Jacobs, A., De Vriendt, E., Schlotter-Weigel, B., Loscher, W., Vondracek, P., Seeman, P., De Jonghe, P., Van Dijck, P., Jordanova, A., Hornemann, T., Timmerman, V.
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<strong>Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I.</strong>
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Am. J. Hum. Genet. 87: 513-522, 2010.
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[PubMed: 20920666]
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Rotthier, A., Baets, J., De Vriendt, E., Jacobs, A., Auer-Grumbach, M., Levy, N., Bonello-Palot, N., Kilic, S. S., Weis, J., Nascimento, A., Swinkels, M., Kruyt, M. C., Jordanova, A., De Jonghe, P., Timmerman, V.
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<strong>Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.</strong>
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[PubMed: 19651702]
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[Full Text: https://doi.org/10.1093/brain/awp198]
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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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Schultze, F.
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<strong>Familiaer auftretendes malum perforans der Fuesse (familiaere lumbale Syringomyelie).</strong>
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Dtsch. Med. Wschr. 43: 545-547, 1917.
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</p>
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<li>
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<p class="mim-text-font">
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Silverman, F. N., Gilden, J. J.
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<strong>Congenital insensitivity to pain, a neurologic syndrome with bizarre skeletal lesions.</strong>
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Radiology 72: 176-190, 1959.
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[PubMed: 13634374]
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[Full Text: https://doi.org/10.1148/72.2.176]
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<p class="mim-text-font">
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Smith, E. M.
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<strong>Familial neurotrophic osseous atrophy: a familial neurotrophic condition of the feet with anesthesia and loss of bone.</strong>
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JAMA 102: 593-595, 1934.
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</li>
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<li>
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<p class="mim-text-font">
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Tocantins, L. M., Reimann, H. A.
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<strong>Perforating ulcers of feet, with osseous atrophy in family with other evidences of dysgenesis (hare lip, cleft palate): an instance of probable myelodysplasia.</strong>
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JAMA 112: 2251-2255, 1939.
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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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Verhoeven, K., Coen, K., De Vriendt, E., Jacobs, A., Van Gerwen, V., Smouts, I., Pou-Serradell, A., Martin, J.-J., Timmerman, V., De Jonghe, P.
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<strong>SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I.</strong>
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Neurology 62: 1001-1002, 2004.
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[PubMed: 15037712]
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[Full Text: https://doi.org/10.1212/01.wnl.0000115388.10828.5c]
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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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Wallace, D. C.
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<strong>A Study of an Hereditary Neuropathy.</strong>
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Thesis: Univ. of Sydney (pub.) 1968.
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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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Wallace, D. C.
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<strong>Hereditary sensory radicular neuropathy. In: Archdall Medical Monograph 8.</strong>
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Sydney: Australasian Med. Pub. Co. 1970.
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Cassandra L. Kniffin - updated : 11/04/2019<br>Carol A. Bocchini - updated : 10/22/2019<br>Cassandra L. Kniffin - updated : 11/12/2010<br>Cassandra L. Kniffin - updated : 9/23/2010<br>Cassandra L. Kniffin - updated : 5/14/2009<br>Cassandra L. Kniffin - updated : 2/6/2009<br>Cassandra L. Kniffin - updated : 9/1/2005<br>Cassandra L. Kniffin - updated : 5/18/2004<br>Denise L. M. Goh - updated : 4/10/2003<br>Carol A. Bocchini - reorganized : 10/5/2001<br>Victor A. McKusick - updated : 9/27/2001<br>Ada Hamosh - updated : 3/2/2001<br>Sheryl A. Jankowski - updated : 12/22/1998<br>Victor A. McKusick - updated : 12/2/1997
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<span class="mim-text-font">
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Victor A. McKusick : 6/2/1986
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carol : 04/02/2021<br>carol : 11/23/2020<br>carol : 11/04/2019<br>ckniffin : 11/04/2019<br>carol : 10/28/2019<br>carol : 10/25/2019<br>carol : 10/23/2019<br>carol : 10/22/2019<br>carol : 07/12/2017<br>carol : 07/11/2017<br>carol : 10/13/2016<br>carol : 05/13/2016<br>alopez : 7/29/2015<br>ckniffin : 7/28/2015<br>carol : 11/19/2014<br>carol : 11/10/2014<br>ckniffin : 10/28/2014<br>ckniffin : 2/10/2014<br>carol : 12/4/2013<br>ckniffin : 12/3/2013<br>alopez : 5/29/2012<br>ckniffin : 5/29/2012<br>carol : 9/16/2011<br>ckniffin : 9/15/2011<br>alopez : 7/29/2011<br>ckniffin : 7/27/2011<br>wwang : 2/23/2011<br>ckniffin : 1/28/2011<br>carol : 11/16/2010<br>ckniffin : 11/12/2010<br>wwang : 10/6/2010<br>ckniffin : 9/23/2010<br>terry : 12/16/2009<br>terry : 6/3/2009<br>wwang : 5/27/2009<br>ckniffin : 5/14/2009<br>wwang : 2/6/2009<br>terry : 2/3/2009<br>carol : 7/12/2007<br>wwang : 9/6/2005<br>ckniffin : 9/1/2005<br>ckniffin : 8/17/2005<br>tkritzer : 9/8/2004<br>ckniffin : 8/27/2004<br>alopez : 8/17/2004<br>terry : 7/27/2004<br>tkritzer : 6/11/2004<br>carol : 5/21/2004<br>ckniffin : 5/18/2004<br>ckniffin : 5/18/2004<br>cwells : 11/5/2003<br>carol : 4/29/2003<br>carol : 4/10/2003<br>carol : 10/5/2001<br>carol : 10/5/2001<br>mcapotos : 10/4/2001<br>terry : 9/27/2001<br>alopez : 3/2/2001<br>terry : 3/2/2001<br>carol : 10/22/1999<br>psherman : 1/6/1999<br>psherman : 12/22/1998<br>carol : 7/8/1998<br>carol : 5/20/1998<br>mark : 12/10/1997<br>terry : 12/2/1997<br>randy : 8/31/1996<br>terry : 5/14/1996<br>terry : 5/6/1996<br>mimadm : 12/2/1994<br>terry : 7/15/1994<br>warfield : 4/21/1994<br>carol : 10/26/1993<br>carol : 8/31/1993<br>supermim : 3/16/1992
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