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<title>
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Entry
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- #618752 - NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT; SCN8
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- OMIM
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<span class="h4">#618752</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/618752"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS202700"> <strong>Phenotypic Series</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="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT) OR (SRP54)" class="mim-tip-hint" title="Clinical Trials" 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=32126&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/gtr/all/tests/?term=618752[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=675767" 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 style="display: table-cell;">Animal Models</div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0112135" 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/618752" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0112135" 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>
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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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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 675767<br />
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<strong>DO:</strong> 0112135<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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618752
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT; SCN8
|
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</span>
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</h3>
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</div>
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<div>
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<br />
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT, WITH OR WITHOUT PANCREATIC DYSFUNCTION AND/OR NEUROLOGIC ABNORMALITIES<br />
|
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SHWACHMAN-DIAMOND SYNDROME-LIKE; SDSL
|
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</span>
|
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</h4>
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</div>
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</div>
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<div>
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<br />
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<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>
|
|
Gene/Locus <br /> MIM number
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
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<tr>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/geneMap/14/166?start=-3&limit=10&highlight=166">
|
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14q13.2
|
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</a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Neutropenia, severe congenital, 8, autosomal dominant
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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/618752"> 618752 </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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SRP54
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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/604857"> 604857 </a>
|
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</span>
|
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</td>
|
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</tr>
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</tbody>
|
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/618752" 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>
|
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<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
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|
|
<div class="btn-group">
|
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|
|
<a href="/phenotypicSeries/PS202700" 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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|
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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/618752" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/618752" 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>
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<div>
|
|
<p />
|
|
</div>
|
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|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
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<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> GROWTH </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Height </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Other </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Poor overall growth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552219&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552219</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</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> Face </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Dysmorphic facial features (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248200007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248200007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424503&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424503</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001999" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001999</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001999" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001999</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Mouth </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Stomatitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61170000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61170000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K12.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K12.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010280</a>]</span><br /> -
|
|
Gingivitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/66383009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">66383009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K05.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K05.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0017574&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017574</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000230" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000230</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000230" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000230</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
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|
|
|
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|
|
|
|
|
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|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Pancreas </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Exocrine pancreatic insufficiency (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/47367009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">47367009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K86.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K86.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0267963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0267963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001738</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001738</a>]</span><br /> -
|
|
Fatty infiltration of the pancreas on imaging (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233757&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233757</a>]</span><br /> -
|
|
Decreased fecal elastase (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233758</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
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|
|
|
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|
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|
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|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Hypotonia (group B) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233756</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Developmental delay (group B) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436424&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436424</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
|
|
Impaired intellectual development (group B) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233753&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233753</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
|
|
Language delay (group B) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233754&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233754</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000750</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Behavioral Psychiatric Manifestations </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Autism spectrum disorder (group B) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233755&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233755</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35919005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35919005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F84.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F84.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F84</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F84.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F84.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/299" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">299</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/299.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">299.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000729" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000729</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
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|
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|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEMATOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Anemia, mild (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858586&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858586</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271737000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271737000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D64.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D64.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/285.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">285.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001903" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001903</a>]</span><br /> -
|
|
Thrombocytopenia, transient (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233764&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233764</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415116008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415116008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302215000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302215000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D69.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D69.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/287.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">287.5</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> IMMUNOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Neutropenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/303011007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">303011007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/165517008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">165517008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84828003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84828003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D70" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D70</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.819" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.819</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D70.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D70.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/288.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/288.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.50</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/288.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0853697&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853697</a>, <a href="https://bioportal.bioontology.org/search?q=C0027947&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027947</a>, <a href="https://bioportal.bioontology.org/search?q=C0023530&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023530</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001875" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001875</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001882</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001875" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001875</a>]</span><br /> -
|
|
Recurrent bacterial infections <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/428875002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">428875002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844383&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844383</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002718" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002718</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002718" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002718</a>]</span><br /> -
|
|
Hypocellular bone marrow <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/416995001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">416995001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/307762000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">307762000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D61.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D61.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151773&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151773</a>]</span><br /> -
|
|
Dysgranulopoiesis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233760&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233760</a>]</span><br /> -
|
|
Maturational arrest of the granulocytic neutrophil line <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233761&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233761</a>]</span><br /> -
|
|
Promyelocytes and myeloblasts contain abnormal cytoplasmic vacuoles <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233762&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233762</a>]</span><br /> -
|
|
Myelocytes contain enlarged ER and autophagosomes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5233763&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5233763</a>]</span><br /> -
|
|
Increased monocytes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0553698&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0553698</a>]</span><br /> -
|
|
Increased lymphocytes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/418010004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">418010004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0853698&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853698</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
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|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset in infancy or early childhood<br /> -
|
|
Two main phenotypic categories (group A and group B)<br /> -
|
|
Patients in group A have normal psychomotor development<br /> -
|
|
Patients in group B have delayed development and/or autistic features<br /> -
|
|
Treatment with G-CSF is partially or not effective<br /> -
|
|
De novo mutation (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2985439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2985439</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
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|
|
</div>
|
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|
|
</div>
|
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|
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|
|
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|
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<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 signal recognition particle, 54-kD gene (SRP54, <a href="/entry/604857#0001">604857.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
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|
|
</div>
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|
|
</div>
|
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<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" 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 id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
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<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
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<h5>
|
|
Neutropenia, severe congenital
|
|
- <a href="/phenotypicSeries/PS202700">PS202700</a>
|
|
- 13 Entries
|
|
</h5>
|
|
</div>
|
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</div>
|
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|
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<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/1/446?start=-3&limit=10&highlight=446"> 1p34.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617014"> Neutropenia, severe congenital, 7, autosomal recessive </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/617014"> 617014 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/138971"> CSF3R </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/138971"> 138971 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/802?start=-3&limit=10&highlight=802"> 1p22.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613107"> Neutropenia, severe congenital 2, autosomal dominant </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/613107"> 613107 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600871"> GFI1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600871"> 600871 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1059?start=-3&limit=10&highlight=1059"> 1q21.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615285"> Neutropenia, severe congenital, 5, autosomal recessive </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/615285"> 615285 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610035"> VPS45 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610035"> 610035 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1187?start=-3&limit=10&highlight=1187"> 1q21.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610738"> Neutropenia, severe congenital 3, autosomal recessive </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/610738"> 610738 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605998"> HAX1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605998"> 605998 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/42?start=-3&limit=10&highlight=42"> 3p25.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616022"> Neutropenia, severe congenital, 6, autosomal recessive </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/616022"> 616022 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616012"> JAGN1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616012"> 616012 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/647?start=-3&limit=10&highlight=647"> 3q21.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620674"> ?Neutropenia, severe congenital, 11, autosomal dominant </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/620674"> 620674 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609213"> SEC61A1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609213"> 609213 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/722?start=-3&limit=10&highlight=722"> 11q13.4 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/619813"> Neutropenia, severe congenital, 9, autosomal dominant </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/619813"> 619813 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616254"> CLPB </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616254"> 616254 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/166?start=-3&limit=10&highlight=166"> 14q13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618752"> Neutropenia, severe congenital, 8, autosomal dominant </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/618752"> 618752 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604857"> SRP54 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604857"> 604857 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/628?start=-3&limit=10&highlight=628"> 17q21.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612541"> Dursun syndrome </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/612541"> 612541 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611045"> G6PC3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611045"> 611045 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/628?start=-3&limit=10&highlight=628"> 17q21.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612541"> Neutropenia, severe congenital 4, autosomal recessive </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/612541"> 612541 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611045"> G6PC3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611045"> 611045 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/964?start=-3&limit=10&highlight=964"> 17q25.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620534"> ?Neutropenia, severe congenital, 10, autosomal recessive </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/620534"> 620534 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604858"> SRP68 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604858"> 604858 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/32?start=-3&limit=10&highlight=32"> 19p13.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/202700"> Neutropenia, severe congenital 1, autosomal dominant </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/202700"> 202700 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/130130"> ELANE </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/130130"> 130130 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/X/253?start=-3&limit=10&highlight=253"> Xp11.23 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/300299"> Neutropenia, severe congenital, X-linked </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
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<p>A number sign (#) is used with this entry because of evidence that autosomal dominant severe congenital neutropenia-8 (SCN8) is caused by heterozygous mutation in the SRP54 gene (<a href="/entry/604857">604857</a>) on chromosome 14q13.</p>
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<p>Autosomal dominant severe congenital neutropenia-8 (SCN8) is a pleiotropic disorder with the consistent feature of decreased neutrophils associated with recurrent bacterial infections apparent from early infancy. Other hematologic parameters are usually normal, although some patients may have mild anemia. Bone marrow examination shows hypocellularity with arrested maturation of the granulocyte lineage at the level of promyelocytes or myeloblasts. Treatment with granulocyte colony-stimulating factor (GCSF; <a href="/entry/138970">138970</a>) is usually ineffective or only partially effective, whereas hematopoietic bone marrow transplantation is effective. A subset of patients have additional features, including exocrine pancreatic insufficiency, which resembles Shwachman-Diamond syndrome (see SDS1, <a href="/entry/260400">260400</a>), and/or neurologic deficits, including developmental delay, impaired intellectual development, speech delay, and/or autistic features (summary by <a href="#2" class="mim-tip-reference" title="Carapito, R., Konantz, M., Paillard, C., Miao, Z., Pichot, A., Leduc, M. S., Yang, Y., Bergstrom, K. L., Mahoney, D. H., Shardy, D. L., Alsaleh, G., Naegely, L., and 38 others. <strong>Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.</strong> J. Clin. Invest. 127: 4090-4103, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28972538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28972538</a>] [<a href="https://doi.org/10.1172/JCI92876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28972538">Carapito et al., 2017</a> and <a href="#1" class="mim-tip-reference" title="Bellanne-Chantelot, C., Schmaltz-Panneau, B., Marty, C., Fenneteau, O., Callebaut, I., Clauin, S., Docet, A., Damaj, G.-L., Leblanc, T., Pellier, I., Stoven, C., Souquere, S., and 26 others. <strong>Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.</strong> Blood 132: 1318-1331, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29914977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29914977</a>] [<a href="https://doi.org/10.1182/blood-2017-12-820308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29914977">Bellanne-Chantelot et al., 2018</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28972538+29914977" 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>For discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (<a href="/entry/202700">202700</a>).</p>
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<p><a href="#2" class="mim-tip-reference" title="Carapito, R., Konantz, M., Paillard, C., Miao, Z., Pichot, A., Leduc, M. S., Yang, Y., Bergstrom, K. L., Mahoney, D. H., Shardy, D. L., Alsaleh, G., Naegely, L., and 38 others. <strong>Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.</strong> J. Clin. Invest. 127: 4090-4103, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28972538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28972538</a>] [<a href="https://doi.org/10.1172/JCI92876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28972538">Carapito et al. (2017)</a> reported 3 unrelated patients with SCN8. All 3 presented in early infancy with severe neutropenia that was not responsive to treatment with GCSF in 2 of the 3 patients. The patients had poor overall growth with short stature. The patient from family A was a 6-year-old boy who presented in the neonatal period with respiratory distress and hypotonia, as well as neutropenia; other hematologic parameters were normal. Hematologic stem cell transplantation was successful with reconstitution. However, this patient also had significant additional systemic abnormalities, including delayed psychomotor development with autistic features, congenital cardiac septal defects requiring surgery, and dysmorphic features, such as low-set asymmetric ears, thin hair, microretrognathia, high-arched palate, small teeth, and pectus carinatum. The affected girl from family B had otherwise normal hematologic parameters and underwent unrelated cord blood transplantation, but died at 16 months of age. No dysmorphic features or developmental delay were noted in this patient. The patient from family C was an 18-year-old Hispanic man with autism who presented with mild anemia in addition to neutropenia associated with recurrent infections at age 2 years; his features were responsive to GCSF treatment and he did not undergo hematopoietic stem cell transplant. Bone marrow examination of all 3 patients showed mildly hypocellular marrow with retarded granulocyte maturation at the promyelocytic stage and hypoplasia of the neutrophil lineage. Myeloblasts and promyelocytes contained cytoplasmic vacuoles. Lymphocytes were mildly increased and platelets were normal. The patients from families A and B had low fecal elastase and fatty infiltration of the pancreas on imaging, suggesting mild pancreatic involvement. Pancreatic abnormalities were not observed in the patient from family C. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28972538" 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="Bellanne-Chantelot, C., Schmaltz-Panneau, B., Marty, C., Fenneteau, O., Callebaut, I., Clauin, S., Docet, A., Damaj, G.-L., Leblanc, T., Pellier, I., Stoven, C., Souquere, S., and 26 others. <strong>Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.</strong> Blood 132: 1318-1331, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29914977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29914977</a>] [<a href="https://doi.org/10.1182/blood-2017-12-820308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29914977">Bellanne-Chantelot et al. (2018)</a> reported 23 French patients with SCN8, including 16 patients with sporadic disease and 7 familial cases. All patients were noted to have profound neutropenia in the first year of life associated with promyelocytic maturation arrest on bone marrow analysis. In most cases, the neutropenia was an isolated finding, and most patients had recurrent and severe bacterial infections, including pneumonia, septicemia, cellulitis, stomatitis/gingivitis, and osteitis. Many had increased monocytes and lymphocytes, 7 had transient moderate anemia, and 2 had transient thrombocytopenia. Treatment with GCSF showed a poor overall response, but despite high doses, none of the patients developed acute myeloid leukemia (AML; see <a href="/entry/601626">601626</a>). Two patients underwent hematopoietic stem cell transplantation with favorable results. Most patients (P1 to P18) had no neurologic symptoms, except for P5, who had a possible family history of a neurodevelopmental disorder. In contrast, a subset of 5 patients (P19 to P23), ranging from 1.5 to 43 years of age, also had neurodevelopmental delay with impaired intellectual development and speech delay and, in one case, epilepsy. These 5 patients also had evidence of subclinical or clinical pancreatic insufficiency, whereas pancreatic involvement was not prominent in the first group of patients. Bone marrow studies showed dysgranulopoiesis with promyelocytes containing cytoplasmic vacuoles, abnormal chromatin, characteristics of apoptosis, enlarged endoplasmic reticulum (ER), and autophagosomes. <a href="#1" class="mim-tip-reference" title="Bellanne-Chantelot, C., Schmaltz-Panneau, B., Marty, C., Fenneteau, O., Callebaut, I., Clauin, S., Docet, A., Damaj, G.-L., Leblanc, T., Pellier, I., Stoven, C., Souquere, S., and 26 others. <strong>Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.</strong> Blood 132: 1318-1331, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29914977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29914977</a>] [<a href="https://doi.org/10.1182/blood-2017-12-820308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29914977">Bellanne-Chantelot et al. (2018)</a> proposed a possible genotype/phenotype correlation in that those with neurologic symptoms had mutations affecting the G2, G4, and G5 elements of the SRP54 GTPase domain, whereas the majority of patients without neurologic involvement had mutations in the G1 element. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29914977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Clinical Variability</em></strong></p><p>
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A subset of patients with SCN8 have been reported to have variable neurodevelopmental delay and/or autistic features. These included 2 of the 3 patients reported by <a href="#2" class="mim-tip-reference" title="Carapito, R., Konantz, M., Paillard, C., Miao, Z., Pichot, A., Leduc, M. S., Yang, Y., Bergstrom, K. L., Mahoney, D. H., Shardy, D. L., Alsaleh, G., Naegely, L., and 38 others. <strong>Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.</strong> J. Clin. Invest. 127: 4090-4103, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28972538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28972538</a>] [<a href="https://doi.org/10.1172/JCI92876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28972538">Carapito et al. (2017)</a> and 5 of the 23 patients reported by <a href="#1" class="mim-tip-reference" title="Bellanne-Chantelot, C., Schmaltz-Panneau, B., Marty, C., Fenneteau, O., Callebaut, I., Clauin, S., Docet, A., Damaj, G.-L., Leblanc, T., Pellier, I., Stoven, C., Souquere, S., and 26 others. <strong>Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.</strong> Blood 132: 1318-1331, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29914977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29914977</a>] [<a href="https://doi.org/10.1182/blood-2017-12-820308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29914977">Bellanne-Chantelot et al. (2018)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28972538+29914977" 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>Heterozygous mutations in the SRP54 gene that were identified in 3 unrelated patients with SCN8 by <a href="#2" class="mim-tip-reference" title="Carapito, R., Konantz, M., Paillard, C., Miao, Z., Pichot, A., Leduc, M. S., Yang, Y., Bergstrom, K. L., Mahoney, D. H., Shardy, D. L., Alsaleh, G., Naegely, L., and 38 others. <strong>Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.</strong> J. Clin. Invest. 127: 4090-4103, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28972538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28972538</a>] [<a href="https://doi.org/10.1172/JCI92876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28972538">Carapito et al. (2017)</a> occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28972538" 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 transmission pattern of SCN8 in 3 families reported by <a href="#1" class="mim-tip-reference" title="Bellanne-Chantelot, C., Schmaltz-Panneau, B., Marty, C., Fenneteau, O., Callebaut, I., Clauin, S., Docet, A., Damaj, G.-L., Leblanc, T., Pellier, I., Stoven, C., Souquere, S., and 26 others. <strong>Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.</strong> Blood 132: 1318-1331, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29914977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29914977</a>] [<a href="https://doi.org/10.1182/blood-2017-12-820308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29914977">Bellanne-Chantelot et al. (2018)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29914977" 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 3 unrelated patients with SCN8, in whom mutations in the SBDS gene (<a href="/entry/607444">607444</a>) and other bone marrow failure syndrome genes were excluded, <a href="#2" class="mim-tip-reference" title="Carapito, R., Konantz, M., Paillard, C., Miao, Z., Pichot, A., Leduc, M. S., Yang, Y., Bergstrom, K. L., Mahoney, D. H., Shardy, D. L., Alsaleh, G., Naegely, L., and 38 others. <strong>Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.</strong> J. Clin. Invest. 127: 4090-4103, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28972538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28972538</a>] [<a href="https://doi.org/10.1172/JCI92876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28972538">Carapito et al. (2017)</a> identified de novo heterozygous mutations in the SRP54 gene (<a href="/entry/604857#0001">604857.0001</a>-<a href="/entry/604857#0003">604857.0003</a>). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, affected highly conserved residues in the GTPase domain and were predicted to affect GTP binding. The patients were identified from a cohort of over 84 patients with a similar phenotype who underwent genetic analysis or were ascertained through collaborative efforts. Patient bone marrow cells showed decreased levels of SRP54 mRNA, and the GTPase activity of the mutant proteins was variably reduced compared to controls. Morpholino knockdown of the srp54 gene resulted in similar phenotypic defects that were rescued by wildtype, but not mutant, SRP54. <a href="#2" class="mim-tip-reference" title="Carapito, R., Konantz, M., Paillard, C., Miao, Z., Pichot, A., Leduc, M. S., Yang, Y., Bergstrom, K. L., Mahoney, D. H., Shardy, D. L., Alsaleh, G., Naegely, L., and 38 others. <strong>Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.</strong> J. Clin. Invest. 127: 4090-4103, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28972538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28972538</a>] [<a href="https://doi.org/10.1172/JCI92876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28972538">Carapito et al. (2017)</a> postulated either haploinsufficiency or a dominant-negative molecular mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28972538" 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 23 French patients with SCN8, including 16 patients with sporadic disease and 7 with familial disease, <a href="#1" class="mim-tip-reference" title="Bellanne-Chantelot, C., Schmaltz-Panneau, B., Marty, C., Fenneteau, O., Callebaut, I., Clauin, S., Docet, A., Damaj, G.-L., Leblanc, T., Pellier, I., Stoven, C., Souquere, S., and 26 others. <strong>Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.</strong> Blood 132: 1318-1331, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29914977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29914977</a>] [<a href="https://doi.org/10.1182/blood-2017-12-820308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29914977">Bellanne-Chantelot et al. (2018)</a> identified heterozygous mutations in the SRP54 gene (see, e.g, <a href="/entry/604857#0001">604857.0001</a>; <a href="/entry/604857#0003">604857.0003</a>; <a href="/entry/604857#0004">604857.0004</a>-<a href="/entry/604857#0006">604857.0006</a>). The mutations, which occurred de novo in the sporadic cases, were all missense variants, except for a recurrent in-frame deletion of conserved residue thr117 (<a href="/entry/604857#0003">604857.0003</a>). All mutations occurred in the GTPase domain. The mutations were initially found by whole-exome sequencing in 3 of 8 unrelated patients with sporadic disease (P11, P13, and P19) and in an affected father and daughter (family 14) out of 6 families with the disease. The mutations were confirmed by Sanger sequencing. The subsequent patients were identified from a second cohort of 66 French probands who underwent direct sequencing of the SRP54 gene. In vitro studies showed that patient granulocytes had decreased cellular proliferation and increased apoptosis compared to controls, as well as evidence of ER stress and induction of autophagy. Knockdown of SRP54 using shRNA in a cell line resulted in similar abnormalities. The authors noted that both neutrophils and pancreatic exocrine cells are highly secretory, possibly rendering them more susceptible to defects in the STP54 gene, which is involved in the maturation of secretory and membrane proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29914977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Carapito, R., Konantz, M., Paillard, C., Miao, Z., Pichot, A., Leduc, M. S., Yang, Y., Bergstrom, K. L., Mahoney, D. H., Shardy, D. L., Alsaleh, G., Naegely, L., and 38 others. <strong>Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.</strong> J. Clin. Invest. 127: 4090-4103, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28972538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28972538</a>] [<a href="https://doi.org/10.1172/JCI92876" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28972538">Carapito et al. (2017)</a> found that morpholino knockdown of the srp54 orthologs in zebrafish resulted in decreased number of basal neutrophils and decreased neutrophil migration and chemotaxis in response to injury compared to controls, as well as impaired pancreatic development and exocrine pancreatic dysfunction. These defects could be rescued with wildtype SRP54. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28972538" 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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Bellanne-Chantelot, C., Schmaltz-Panneau, B., Marty, C., Fenneteau, O., Callebaut, I., Clauin, S., Docet, A., Damaj, G.-L., Leblanc, T., Pellier, I., Stoven, C., Souquere, S., and 26 others.
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Blood 132: 1318-1331, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29914977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29914977</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29914977" 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/10.1182/blood-2017-12-820308" target="_blank">Full Text</a>]
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Carapito, R., Konantz, M., Paillard, C., Miao, Z., Pichot, A., Leduc, M. S., Yang, Y., Bergstrom, K. L., Mahoney, D. H., Shardy, D. L., Alsaleh, G., Naegely, L., and 38 others.
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<strong>Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.</strong>
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J. Clin. Invest. 127: 4090-4103, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28972538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28972538</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28972538" 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/10.1172/JCI92876" target="_blank">Full Text</a>]
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Cassandra L. Kniffin : 01/27/2020
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alopez : 01/31/2020
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ckniffin : 01/29/2020
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NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT; SCN8
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NEUTROPENIA, SEVERE CONGENITAL, 8, AUTOSOMAL DOMINANT, WITH OR WITHOUT PANCREATIC DYSFUNCTION AND/OR NEUROLOGIC ABNORMALITIES<br />
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SHWACHMAN-DIAMOND SYNDROME-LIKE; SDSL
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<strong>ORPHA:</strong> 675767;
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<strong>DO:</strong> 0112135;
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14q13.2
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Neutropenia, severe congenital, 8, autosomal dominant
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618752
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Autosomal dominant
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SRP54
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604857
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<p>A number sign (#) is used with this entry because of evidence that autosomal dominant severe congenital neutropenia-8 (SCN8) is caused by heterozygous mutation in the SRP54 gene (604857) on chromosome 14q13.</p>
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<p>Autosomal dominant severe congenital neutropenia-8 (SCN8) is a pleiotropic disorder with the consistent feature of decreased neutrophils associated with recurrent bacterial infections apparent from early infancy. Other hematologic parameters are usually normal, although some patients may have mild anemia. Bone marrow examination shows hypocellularity with arrested maturation of the granulocyte lineage at the level of promyelocytes or myeloblasts. Treatment with granulocyte colony-stimulating factor (GCSF; 138970) is usually ineffective or only partially effective, whereas hematopoietic bone marrow transplantation is effective. A subset of patients have additional features, including exocrine pancreatic insufficiency, which resembles Shwachman-Diamond syndrome (see SDS1, 260400), and/or neurologic deficits, including developmental delay, impaired intellectual development, speech delay, and/or autistic features (summary by Carapito et al., 2017 and Bellanne-Chantelot et al., 2018). </p><p>For discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700).</p>
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<p>Carapito et al. (2017) reported 3 unrelated patients with SCN8. All 3 presented in early infancy with severe neutropenia that was not responsive to treatment with GCSF in 2 of the 3 patients. The patients had poor overall growth with short stature. The patient from family A was a 6-year-old boy who presented in the neonatal period with respiratory distress and hypotonia, as well as neutropenia; other hematologic parameters were normal. Hematologic stem cell transplantation was successful with reconstitution. However, this patient also had significant additional systemic abnormalities, including delayed psychomotor development with autistic features, congenital cardiac septal defects requiring surgery, and dysmorphic features, such as low-set asymmetric ears, thin hair, microretrognathia, high-arched palate, small teeth, and pectus carinatum. The affected girl from family B had otherwise normal hematologic parameters and underwent unrelated cord blood transplantation, but died at 16 months of age. No dysmorphic features or developmental delay were noted in this patient. The patient from family C was an 18-year-old Hispanic man with autism who presented with mild anemia in addition to neutropenia associated with recurrent infections at age 2 years; his features were responsive to GCSF treatment and he did not undergo hematopoietic stem cell transplant. Bone marrow examination of all 3 patients showed mildly hypocellular marrow with retarded granulocyte maturation at the promyelocytic stage and hypoplasia of the neutrophil lineage. Myeloblasts and promyelocytes contained cytoplasmic vacuoles. Lymphocytes were mildly increased and platelets were normal. The patients from families A and B had low fecal elastase and fatty infiltration of the pancreas on imaging, suggesting mild pancreatic involvement. Pancreatic abnormalities were not observed in the patient from family C. </p><p>Bellanne-Chantelot et al. (2018) reported 23 French patients with SCN8, including 16 patients with sporadic disease and 7 familial cases. All patients were noted to have profound neutropenia in the first year of life associated with promyelocytic maturation arrest on bone marrow analysis. In most cases, the neutropenia was an isolated finding, and most patients had recurrent and severe bacterial infections, including pneumonia, septicemia, cellulitis, stomatitis/gingivitis, and osteitis. Many had increased monocytes and lymphocytes, 7 had transient moderate anemia, and 2 had transient thrombocytopenia. Treatment with GCSF showed a poor overall response, but despite high doses, none of the patients developed acute myeloid leukemia (AML; see 601626). Two patients underwent hematopoietic stem cell transplantation with favorable results. Most patients (P1 to P18) had no neurologic symptoms, except for P5, who had a possible family history of a neurodevelopmental disorder. In contrast, a subset of 5 patients (P19 to P23), ranging from 1.5 to 43 years of age, also had neurodevelopmental delay with impaired intellectual development and speech delay and, in one case, epilepsy. These 5 patients also had evidence of subclinical or clinical pancreatic insufficiency, whereas pancreatic involvement was not prominent in the first group of patients. Bone marrow studies showed dysgranulopoiesis with promyelocytes containing cytoplasmic vacuoles, abnormal chromatin, characteristics of apoptosis, enlarged endoplasmic reticulum (ER), and autophagosomes. Bellanne-Chantelot et al. (2018) proposed a possible genotype/phenotype correlation in that those with neurologic symptoms had mutations affecting the G2, G4, and G5 elements of the SRP54 GTPase domain, whereas the majority of patients without neurologic involvement had mutations in the G1 element. </p><p><strong><em>Clinical Variability</em></strong></p><p>
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A subset of patients with SCN8 have been reported to have variable neurodevelopmental delay and/or autistic features. These included 2 of the 3 patients reported by Carapito et al. (2017) and 5 of the 23 patients reported by Bellanne-Chantelot et al. (2018). </p>
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<p>Heterozygous mutations in the SRP54 gene that were identified in 3 unrelated patients with SCN8 by Carapito et al. (2017) occurred de novo. </p><p>The transmission pattern of SCN8 in 3 families reported by Bellanne-Chantelot et al. (2018) was consistent with autosomal dominant inheritance. </p>
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<p>In 3 unrelated patients with SCN8, in whom mutations in the SBDS gene (607444) and other bone marrow failure syndrome genes were excluded, Carapito et al. (2017) identified de novo heterozygous mutations in the SRP54 gene (604857.0001-604857.0003). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, affected highly conserved residues in the GTPase domain and were predicted to affect GTP binding. The patients were identified from a cohort of over 84 patients with a similar phenotype who underwent genetic analysis or were ascertained through collaborative efforts. Patient bone marrow cells showed decreased levels of SRP54 mRNA, and the GTPase activity of the mutant proteins was variably reduced compared to controls. Morpholino knockdown of the srp54 gene resulted in similar phenotypic defects that were rescued by wildtype, but not mutant, SRP54. Carapito et al. (2017) postulated either haploinsufficiency or a dominant-negative molecular mechanism. </p><p>In 23 French patients with SCN8, including 16 patients with sporadic disease and 7 with familial disease, Bellanne-Chantelot et al. (2018) identified heterozygous mutations in the SRP54 gene (see, e.g, 604857.0001; 604857.0003; 604857.0004-604857.0006). The mutations, which occurred de novo in the sporadic cases, were all missense variants, except for a recurrent in-frame deletion of conserved residue thr117 (604857.0003). All mutations occurred in the GTPase domain. The mutations were initially found by whole-exome sequencing in 3 of 8 unrelated patients with sporadic disease (P11, P13, and P19) and in an affected father and daughter (family 14) out of 6 families with the disease. The mutations were confirmed by Sanger sequencing. The subsequent patients were identified from a second cohort of 66 French probands who underwent direct sequencing of the SRP54 gene. In vitro studies showed that patient granulocytes had decreased cellular proliferation and increased apoptosis compared to controls, as well as evidence of ER stress and induction of autophagy. Knockdown of SRP54 using shRNA in a cell line resulted in similar abnormalities. The authors noted that both neutrophils and pancreatic exocrine cells are highly secretory, possibly rendering them more susceptible to defects in the STP54 gene, which is involved in the maturation of secretory and membrane proteins. </p>
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<p>Carapito et al. (2017) found that morpholino knockdown of the srp54 orthologs in zebrafish resulted in decreased number of basal neutrophils and decreased neutrophil migration and chemotaxis in response to injury compared to controls, as well as impaired pancreatic development and exocrine pancreatic dysfunction. These defects could be rescued with wildtype SRP54. </p>
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<strong>REFERENCES</strong>
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Bellanne-Chantelot, C., Schmaltz-Panneau, B., Marty, C., Fenneteau, O., Callebaut, I., Clauin, S., Docet, A., Damaj, G.-L., Leblanc, T., Pellier, I., Stoven, C., Souquere, S., and 26 others.
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<strong>Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.</strong>
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Blood 132: 1318-1331, 2018.
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[PubMed: 29914977]
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[Full Text: https://doi.org/10.1182/blood-2017-12-820308]
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Carapito, R., Konantz, M., Paillard, C., Miao, Z., Pichot, A., Leduc, M. S., Yang, Y., Bergstrom, K. L., Mahoney, D. H., Shardy, D. L., Alsaleh, G., Naegely, L., and 38 others.
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<strong>Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features.</strong>
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J. Clin. Invest. 127: 4090-4103, 2017.
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[PubMed: 28972538]
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[Full Text: https://doi.org/10.1172/JCI92876]
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Creation Date:
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<span class="mim-text-font">
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Cassandra L. Kniffin : 01/27/2020
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<span class="mim-text-font">
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alopez : 01/31/2020<br>ckniffin : 01/29/2020
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