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Entry
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- #159550 - ATAXIA-PANCYTOPENIA SYNDROME; ATXPC
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- OMIM
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<p>
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<span class="h4">#159550</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/159550"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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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="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=ATAXIA-PANCYTOPENIA SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=2383&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK435692/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/5018" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=159550[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=2585" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/818977e7-19f4-4921-ac39-f12421a2e9e9/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</a>
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</span>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:159550" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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<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>SNOMEDCT:</strong> 768556005<br />
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<strong>ORPHA:</strong> 2585<br />
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">ICD+</a>
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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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159550
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</span>
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</span>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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ATAXIA-PANCYTOPENIA SYNDROME; ATXPC
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</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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MYELOCEREBELLAR DISORDER
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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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</div>
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</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/7/414?start=-3&limit=10&highlight=414">
|
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7q21.2
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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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Ataxia-pancytopenia syndrome
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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/159550"> 159550 </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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</td>
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<td>
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<span class="mim-font">
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SAMD9L
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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/611170"> 611170 </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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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/159550" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
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<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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/159550" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/159550" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<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>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- 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 />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> HEAD & NECK </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Eyes </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Cerebellar ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
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Gait instability <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22631008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22631008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231686</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002317" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002317</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002317" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002317</a>]</span><br /> -
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Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
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|
Dysmetria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32566006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32566006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234162&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234162</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001310" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001310</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001310" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001310</a>]</span><br /> -
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Hyperreflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> -
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|
Extensor plantar responses <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246586009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246586009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366575004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366575004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034935</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span><br /> -
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|
Ankle clonus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39055007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39055007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238651&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238651</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011448" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011448</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011448" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011448</a>]</span><br /> -
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Cerebellar atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740279</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span><br /> -
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Cerebellar degeneration <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95646004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95646004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0262404&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0262404</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span><br /> -
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White matter abnormalities (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0948163&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0948163</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002500" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002500</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002500" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002500</a>]</span><br />
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</span>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Peripheral Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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|
- Distal sensory impairment (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847584&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847584</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002936</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002936</a>]</span><br /> -
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Decreased nerve conduction velocities (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857640&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857640</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000762</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000762</a>]</span><br />
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</span>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<em> Behavioral Psychiatric Manifestations </em>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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- ADHD <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7461003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7461003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/406506008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">406506008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F90</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F90.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F90.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/314.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">314.01</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/314" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">314</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/314.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">314.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1263846&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1263846</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000752" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000752</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0007018" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007018</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007018" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007018</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> HEMATOLOGY </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Pancytopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/127034005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">127034005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D61.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D61.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/284.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">284.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0030312&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030312</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001876" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001876</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001876" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001876</a>]</span><br /> -
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Anemia <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">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002871&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002871</a>, <a href="https://bioportal.bioontology.org/search?q=C1000483&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1000483</a> 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> <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 /> -
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Thrombocytopenia <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">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392386</a>, <a href="https://bioportal.bioontology.org/search?q=C0040034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040034</a> 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> <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 /> -
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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 /> -
|
|
Macrocytosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/72826005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">72826005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397073000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397073000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0684332&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0684332</a>, <a href="https://bioportal.bioontology.org/search?q=C2004480&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2004480</a>, <a href="https://bioportal.bioontology.org/search?q=C0085662&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085662</a>]</span><br /> -
|
|
Bone marrow shows hypocellularity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435577&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435577</a>]</span><br /> -
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Dysplastic features <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435578&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435578</a>]</span><br /> -
|
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Monosomy 7 in bone marrow cells <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435579&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435579</a>]</span><br /> -
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Myelodysplastic syndrome (MDS) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109995007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109995007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/128623006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">128623006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D46" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D46</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D46.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D46.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/238.75" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">238.75</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3463824&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3463824</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002863" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002863</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002863" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002863</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> IMMUNOLOGY </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Recurrent infections <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/451991000124106" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">451991000124106</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239998&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239998</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002719</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002719</a>]</span><br /> -
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Immunodeficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/234532001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">234532001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D84.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D84.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/279.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">279.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4284394&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4284394</a>, <a href="https://bioportal.bioontology.org/search?q=C0021051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0021051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002721" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002721</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002721" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002721</a>]</span><br /> -
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Hypogammaglobulinemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/119250001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">119250001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D80.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D80.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/279.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">279.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086438&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086438</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004313</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004313</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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- Caused by mutation in the sterile alpha motif domain-containing protein 9-like gene (SAMD9L, <a href="/entry/611170#0001">611170.0001</a>)<br />
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<p>A number sign (#) is used with this entry because of evidence that ataxia-pancytopenia syndrome (ATXPC) is caused by heterozygous mutation in the SAMD9L gene (<a href="/entry/611170">611170</a>) on chromosome 7q21.</p><p>Heterozygous mutation in the SAMD9L gene can also cause monosomy 7 myelodysplasia and leukemia syndrome-1 (M7MLS1; <a href="/entry/252270">252270</a>), which shows some overlapping features.</p>
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<p>Ataxia-pancytopenia syndrome (ATXPC) is an autosomal dominant disorder characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to bone marrow failure and myeloid leukemia. The germline genetic defect is associated with somatic loss of chromosome 7 (monosomy 7) resulting in the deletion of several genes on chromosome 7 that may predispose to the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) (summary by <a href="#1" class="mim-tip-reference" title="Chen, D.-H., Below, J. E., Shimamura, A., Keel, S. B., Matsushita, M., Wolff, J., Sul, Y., Bonkowski, E., Castella, M., Taniguchi, T., Nickerson, D., Papayannopoulou, T., Bird, T. D., Raskind, W. H. <strong>Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L.</strong> Am. J. Hum. Genet. 98: 1146-1158, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27259050[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.04.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259050">Chen et al., 2016</a> and <a href="#7" class="mim-tip-reference" title="Tesi, B., Davidsson, J., Voss, M., Rahikkala, E., Holmes, T. D., Chiang, S. C. C., Komulainen-Ebrahim, J., Gorcenco, S., Nilsson, A. R., Ripperger, T., Kokkonen, H., Bryder, D., and 13 others. <strong>Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms.</strong> Blood 129: 2266-2279, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28202457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28202457</a>] [<a href="https://doi.org/10.1182/blood-2016-10-743302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28202457">Tesi et al., 2017</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28202457+27259050" 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>Li et al. (<a href="#5" class="mim-tip-reference" title="Li, F. P., Potter, N. U., Buchanan, G. R., Vawter, G., Whang-Peng, J., Rosen, R. B. <strong>A family with acute leukemia, hypoplastic anemia and cerebellar ataxia: association with bone marrow C-monosomy.</strong> Am. J. Med. 65: 933-940, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/283689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">283689</a>] [<a href="https://doi.org/10.1016/0002-9343(78)90744-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="283689">1978</a>, <a href="#4" class="mim-tip-reference" title="Li, F. P., Hecht, F., Kaiser-McCaw, B., Baranko, P. V., Potter, N. U. <strong>Ataxia-pancytopenia: syndrome of cerebellar ataxia, hypoplastic anemia, monosomy 7, and acute myelogenous leukemia.</strong> Cancer Genet. Cytogenet. 4: 189-196, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6947857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6947857</a>] [<a href="https://doi.org/10.1016/0165-4608(81)90013-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6947857">1981</a>) described a family with ataxia and pancytopenia. The propositus, the youngest of a sibship of 5, had cerebellar ataxia, developed hypoplastic anemia at age 3 years, and died of acute myelomonocytic leukemia at age 7. Serial cytogenetic studies of his hypoplastic bone marrow over a 25-month period showed progressive expansion of a clone of cells with monosomy 7 (<a href="/entry/252270">252270</a>). Cerebellar ataxia was found in the proband's father and all 4 sibs. Two brothers, including 1 with monosomy 7, died with hypoplastic anemia at ages 5 and 9 years, and a third brother died with acute myelocytic leukemia at age 10 years. The only surviving sib at the time of the report of <a href="#4" class="mim-tip-reference" title="Li, F. P., Hecht, F., Kaiser-McCaw, B., Baranko, P. V., Potter, N. U. <strong>Ataxia-pancytopenia: syndrome of cerebellar ataxia, hypoplastic anemia, monosomy 7, and acute myelogenous leukemia.</strong> Cancer Genet. Cytogenet. 4: 189-196, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6947857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6947857</a>] [<a href="https://doi.org/10.1016/0165-4608(81)90013-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6947857">Li et al. (1981)</a> was a 19-year-old sister who had unexplained anemia, decreased mitotic activity in the bone marrow, and a slowly progressive cerebellar ataxia. In addition to progressive cerebellar ataxia, the father had marked progressive cerebellar ataxia, brisk deep tendon reflexes, bilateral Babinski reflexes, and diminished vibratory sensation in the legs. Unsteady gait first brought the father to medical attention at age 28 years and he was not able to work thereafter. Computed tomographic scans of the father, the sister, and 1 brother showed cerebellar atrophy. Autopsy in 1 brother showed marked cerebellar atrophy and loss of 90% of the Purkinje cells; the spinal column was normal. By 1989, the sister had given up her career in nursing because of increasingly severe cerebellar ataxia and the father was largely confined at home (<a href="#6" class="mim-tip-reference" title="Li, F. P. <strong>Personal Communication.</strong> Boston, Mass. 10/3/1989."None>Li, 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6947857+283689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a family reported by <a href="#2" class="mim-tip-reference" title="Daghistani, D., Curless, R., Toledano, S. R., Ayyar, D. R. <strong>Ataxia-pancytopenia and monosomy 7 syndrome.</strong> J. Pediat. 115: 108-110, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2738778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2738778</a>] [<a href="https://doi.org/10.1016/s0022-3476(89)80342-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2738778">Daghistani et al. (1989)</a>, the proband, a 5-year-old boy, presented with left facial abscess and pancytopenia, following a 2-year history of mild incoordination. He had nystagmus and dysmetria. Monosomy 7 was found. He died at the age of about 6 years from pancytopenia. The sister of the proband, 12 years old at the time of report, had the onset of mild progressive unsteadiness at the age of 7 years. She had nystagmus and dysarthria. Nerve conduction studies showed reduced velocities in both sibs. The mother of the 2 children had had onset of incoordination before age 5. She showed severe gait ataxia and pronounced dysarthria with upper extremity dysmetria and horizontal and vertical nystagmus. Nerve conduction studies showed reduced velocities. The father was normal neurologically and hematologically. None of the 3 patients had oculocutaneous telangiectasia, scoliosis, or cardiac dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2738778" 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="Chen, D.-H., Below, J. E., Shimamura, A., Keel, S. B., Matsushita, M., Wolff, J., Sul, Y., Bonkowski, E., Castella, M., Taniguchi, T., Nickerson, D., Papayannopoulou, T., Bird, T. D., Raskind, W. H. <strong>Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L.</strong> Am. J. Hum. Genet. 98: 1146-1158, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27259050[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.04.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259050">Chen et al. (2016)</a> reported a large multigenerational family (UW-AP) of German, Irish, and Native American descent in which at least 9 individuals had ataxia-pancytopenia syndrome. The phenotype was highly variable, with onset of symptoms ranging from 6 to 62 years of age, although manifestations could be detected earlier by examination. Neurologic features included gait imbalance, horizontal and vertical nystagmus, dysmetria, hyperreflexia, ankle clonus, and sometimes extensor plantar responses. Brain imaging, performed in 2 patients, showed cerebellar atrophy or degeneration. Hematologic abnormalities, which were variable and sometimes intermittent, included anemia, leukopenia, and thrombocytopenia. Four adult sibs were described in detail. The first patient presented with pancytopenia at age 3 months. Bone marrow aspirate at age 11 years showed hypoplasia with normal maturation and some immature forms. He developed slowly progressive balance issues at age 30, and by age 47, he had nystagmus, dysarthria, dysmetria, hyperreflexia, and normal gait but difficulty with tandem walking. His brother presented at age 1 year with thrombocytopenia that later evolved to pancytopenia. He developed a retroperitoneal bleed and died at age 16 years. He had no neurologic manifestations or ataxia, but postmortem examination showed cerebellar atrophy with severe loss of Purkinje cells and gliosis in the hippocampus. The third patient developed unsteady gait at age 25 that progressed to severe ataxia requiring a walker by age 38. Other features included severe dysarthria, nystagmus, and hyperreflexia. Laboratory studies showed mild leukopenia and mild to moderate thrombocytopenia. The fourth patient first noted balance problems at age 36, but physical examination at age 25 had shown nystagmus and ankle clonus. She developed intermittent mild neutropenia and thrombocytopenia after age 45. <a href="#1" class="mim-tip-reference" title="Chen, D.-H., Below, J. E., Shimamura, A., Keel, S. B., Matsushita, M., Wolff, J., Sul, Y., Bonkowski, E., Castella, M., Taniguchi, T., Nickerson, D., Papayannopoulou, T., Bird, T. D., Raskind, W. H. <strong>Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L.</strong> Am. J. Hum. Genet. 98: 1146-1158, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27259050[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.04.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259050">Chen et al. (2016)</a> noted that the severities of the hematologic and neurologic abnormalities were not concordant in this family. None of the patients had dysplastic marrow changes and none developed myelodysplasia or leukemia. Patient cells showed normal DNA repair responses, no increased sensitivity to ionizing radiation, and normal telomere lengths. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27259050" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Gonzalez-del Angel, A., Cervera, M., Gomez, L., Perez-Vera, P., Orozco, L., Carnevale, A., Del Castillo, V. <strong>Ataxia-pancytopenia syndrome.</strong> Am. J. Med. Genet. 90: 252-254, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10678666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10678666</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(20000131)90:3<252::aid-ajmg14>3.3.co;2-m" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10678666">Gonzalez-del Angel et al. (2000)</a> described a Mexican girl who developed cerebellar ataxia at age 3 years and pancytopenia at age 13 years. Cerebral computed tomography scan and magnetic resonance imaging showed evidence of severe cerebellar atrophy. Telangiectases were not present, and immunoglobulins and alpha-fetoprotein levels were normal, making ataxia-telangiectasia (<a href="/entry/208900">208900</a>) unlikely. Cytogenetic studies showed no abnormalities except for an increased frequency of chromosomal aberrations in response to bleomycin. The phenotype was considered consistent with the ataxia-pancytopenia syndrome, although monosomy of chromosome 7 was not found in bone marrow. The sensitivity to bleomycin suggested this may be a chromosomal instability disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10678666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Tesi, B., Davidsson, J., Voss, M., Rahikkala, E., Holmes, T. D., Chiang, S. C. C., Komulainen-Ebrahim, J., Gorcenco, S., Nilsson, A. R., Ripperger, T., Kokkonen, H., Bryder, D., and 13 others. <strong>Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms.</strong> Blood 129: 2266-2279, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28202457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28202457</a>] [<a href="https://doi.org/10.1182/blood-2016-10-743302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28202457">Tesi et al. (2017)</a> reported 2 unrelated families of Swedish and Finnish origin, respectively, with a syndromic disorder characterized by hematologic and neurologic dysfunction. The proband in the first family was a 4-year-old boy with a history of CMV infection, trilineage cytopenia, hypogammaglobulinemia, and MDS associated with monosomy 7. He underwent successful hematopoietic stem cell transplantation and thereafter developed neurologic symptoms, including nystagmus, unsteady gait, and lower limb stiffness and weakness. Brain imaging showed white matter abnormalities and progressive cerebellar degeneration. His grandfather developed MDS at age 56 years and did not have monosomy 7. He had mildly impaired balance. None of the other affected family members had MDS, but several had transient thrombocytopenia or pancytopenia, often associated with uniparental disomy of chromosome 7q or a revertant SAMD9L variant. Most, but not all, patients had mild neurologic symptoms, mainly nystagmus and impaired balance. In the second family, a mother and her 2 affected children had recurrent infections suggesting mild immunodeficiency. They also had variable neurologic features, such as nystagmus, balance problems, and attention deficit-hyperactivity disorder. The 2 children had thrombocytopenia and pancytopenia, one with a hypoplastic bone marrow and the other with dysplastic megakaryocytes and MDS. Although both of these patients had uniparental disomy of 7q, only 1 had monosomy 7; the latter patient underwent hematopoietic stem cell transplantation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28202457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of ATXPC in the families reported by <a href="#5" class="mim-tip-reference" title="Li, F. P., Potter, N. U., Buchanan, G. R., Vawter, G., Whang-Peng, J., Rosen, R. B. <strong>A family with acute leukemia, hypoplastic anemia and cerebellar ataxia: association with bone marrow C-monosomy.</strong> Am. J. Med. 65: 933-940, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/283689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">283689</a>] [<a href="https://doi.org/10.1016/0002-9343(78)90744-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="283689">Li et al. (1978)</a> and <a href="#1" class="mim-tip-reference" title="Chen, D.-H., Below, J. E., Shimamura, A., Keel, S. B., Matsushita, M., Wolff, J., Sul, Y., Bonkowski, E., Castella, M., Taniguchi, T., Nickerson, D., Papayannopoulou, T., Bird, T. D., Raskind, W. H. <strong>Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L.</strong> Am. J. Hum. Genet. 98: 1146-1158, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27259050[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.04.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259050">Chen et al. (2016)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=283689+27259050" 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 ATXPC in the families reported by <a href="#7" class="mim-tip-reference" title="Tesi, B., Davidsson, J., Voss, M., Rahikkala, E., Holmes, T. D., Chiang, S. C. C., Komulainen-Ebrahim, J., Gorcenco, S., Nilsson, A. R., Ripperger, T., Kokkonen, H., Bryder, D., and 13 others. <strong>Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms.</strong> Blood 129: 2266-2279, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28202457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28202457</a>] [<a href="https://doi.org/10.1182/blood-2016-10-743302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28202457">Tesi et al. (2017)</a> was consistent with autosomal dominant inheritance with incomplete penetrance and variable expressivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28202457" 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 affected members of 2 unrelated families with ATXPC, including the family originally reported by <a href="#5" class="mim-tip-reference" title="Li, F. P., Potter, N. U., Buchanan, G. R., Vawter, G., Whang-Peng, J., Rosen, R. B. <strong>A family with acute leukemia, hypoplastic anemia and cerebellar ataxia: association with bone marrow C-monosomy.</strong> Am. J. Med. 65: 933-940, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/283689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">283689</a>] [<a href="https://doi.org/10.1016/0002-9343(78)90744-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="283689">Li et al. (1978)</a>, <a href="#1" class="mim-tip-reference" title="Chen, D.-H., Below, J. E., Shimamura, A., Keel, S. B., Matsushita, M., Wolff, J., Sul, Y., Bonkowski, E., Castella, M., Taniguchi, T., Nickerson, D., Papayannopoulou, T., Bird, T. D., Raskind, W. H. <strong>Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L.</strong> Am. J. Hum. Genet. 98: 1146-1158, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27259050[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.04.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259050">Chen et al. (2016)</a> identified 2 different heterozygous missense mutations in the SAMD9L gene (H880Q, <a href="/entry/611170#0001">611170.0001</a> and C1196S, <a href="/entry/611170#0002">611170.0002</a>). The mutation in the first family was found by a combination of linkage analysis and exome sequencing. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=283689+27259050" 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 affected members of 2 unrelated families with ATXPC, <a href="#7" class="mim-tip-reference" title="Tesi, B., Davidsson, J., Voss, M., Rahikkala, E., Holmes, T. D., Chiang, S. C. C., Komulainen-Ebrahim, J., Gorcenco, S., Nilsson, A. R., Ripperger, T., Kokkonen, H., Bryder, D., and 13 others. <strong>Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms.</strong> Blood 129: 2266-2279, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28202457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28202457</a>] [<a href="https://doi.org/10.1182/blood-2016-10-743302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28202457">Tesi et al. (2017)</a> identified germline heterozygous gain-of-function mutations in the SAMD9L gene (R986C, <a href="/entry/611170#0003">611170.0003</a> and I891T, <a href="/entry/611170#0004">611170.0004</a>). The mutations, which were found by whole-exome or Sanger sequencing, segregated with the disorder in the family, although there was variable expressivity. In vitro functional expression studies in cells transfected with the mutations showed that they augmented the growth-suppressing activity of SAMD9L and halted cell proliferation compared to wildtype, consistent with a gain-of-function effect. Some patients developed MDS associated with monosomy 7; loss of chromosome 7 in these patients eliminated the SAMD9L mutations, suggesting that the SAMD9L mutations were not themselves conducive to tumor cell propagation, but that cytogenetic events eradicating the chromosome may explain the predisposition to MDS. This would be an example of 'adaptation by aneuploidy.' In contrast, other family members had less severe or limited manifestations associated with uniparental disomy of 7q or revertant SAMD9L mosaicism that likely mitigated the pathogenic effects of the familial mutations by acting as loss-of-function alleles. In in vitro studies, <a href="#7" class="mim-tip-reference" title="Tesi, B., Davidsson, J., Voss, M., Rahikkala, E., Holmes, T. D., Chiang, S. C. C., Komulainen-Ebrahim, J., Gorcenco, S., Nilsson, A. R., Ripperger, T., Kokkonen, H., Bryder, D., and 13 others. <strong>Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms.</strong> Blood 129: 2266-2279, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28202457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28202457</a>] [<a href="https://doi.org/10.1182/blood-2016-10-743302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28202457">Tesi et al. (2017)</a> found that stimulation of CD34+ hematopoietic stem cells with IFNA (<a href="/entry/147660">147660</a>) or IFNG (<a href="/entry/147570">147570</a>) induced SAMD9L expression. These findings provided a mechanism by which an immune response may indirectly lead to cytopenia, thus providing a basis for the selection of somatic SAMD9L revertant mutants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28202457" 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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Chen, D.-H., Below, J. E., Shimamura, A., Keel, S. B., Matsushita, M., Wolff, J., Sul, Y., Bonkowski, E., Castella, M., Taniguchi, T., Nickerson, D., Papayannopoulou, T., Bird, T. D., Raskind, W. H.
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<strong>Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L.</strong>
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Am. J. Hum. Genet. 98: 1146-1158, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27259050[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27259050" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2016.04.009" target="_blank">Full Text</a>]
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Daghistani, D., Curless, R., Toledano, S. R., Ayyar, D. R.
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<strong>Ataxia-pancytopenia and monosomy 7 syndrome.</strong>
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J. Pediat. 115: 108-110, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2738778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2738778</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2738778" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(89)80342-7" target="_blank">Full Text</a>]
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Gonzalez-del Angel, A., Cervera, M., Gomez, L., Perez-Vera, P., Orozco, L., Carnevale, A., Del Castillo, V.
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<strong>Ataxia-pancytopenia syndrome.</strong>
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Am. J. Med. Genet. 90: 252-254, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10678666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10678666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10678666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/(sici)1096-8628(20000131)90:3<252::aid-ajmg14>3.3.co;2-m" target="_blank">Full Text</a>]
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Li, F. P., Hecht, F., Kaiser-McCaw, B., Baranko, P. V., Potter, N. U.
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<strong>Ataxia-pancytopenia: syndrome of cerebellar ataxia, hypoplastic anemia, monosomy 7, and acute myelogenous leukemia.</strong>
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Cancer Genet. Cytogenet. 4: 189-196, 1981.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6947857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6947857</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6947857" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Li, F. P., Potter, N. U., Buchanan, G. R., Vawter, G., Whang-Peng, J., Rosen, R. B.
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<strong>A family with acute leukemia, hypoplastic anemia and cerebellar ataxia: association with bone marrow C-monosomy.</strong>
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Am. J. Med. 65: 933-940, 1978.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/283689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">283689</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=283689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Tesi, B., Davidsson, J., Voss, M., Rahikkala, E., Holmes, T. D., Chiang, S. C. C., Komulainen-Ebrahim, J., Gorcenco, S., Nilsson, A. R., Ripperger, T., Kokkonen, H., Bryder, D., and 13 others.
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<strong>Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms.</strong>
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Blood 129: 2266-2279, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28202457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28202457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28202457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Cassandra L. Kniffin - updated : 12/07/2020
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Cassandra L. Kniffin - updated : 6/22/2016<br>Cassandra L. Kniffin - updated : 12/30/2008<br>Victor A. McKusick - updated : 2/24/2000
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 12/10/2020
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ckniffin : 12/07/2020<br>alopez : 01/02/2019<br>joanna : 07/01/2016<br>alopez : 6/30/2016<br>ckniffin : 6/22/2016<br>joanna : 7/20/2012<br>wwang : 1/15/2009<br>wwang : 1/15/2009<br>ckniffin : 12/30/2008<br>carol : 4/2/2001<br>terry : 2/24/2000<br>mimadm : 12/2/1994<br>davew : 7/14/1994<br>warfield : 4/21/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>carol : 12/9/1989
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<strong>#</strong> 159550
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ATAXIA-PANCYTOPENIA SYNDROME; ATXPC
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<em>Alternative titles; symbols</em>
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MYELOCEREBELLAR DISORDER
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<strong>SNOMEDCT:</strong> 768556005;
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<strong>ORPHA:</strong> 2585;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus <br /> MIM number
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7q21.2
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Ataxia-pancytopenia syndrome
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159550
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Autosomal dominant
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3
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SAMD9L
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611170
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<p>A number sign (#) is used with this entry because of evidence that ataxia-pancytopenia syndrome (ATXPC) is caused by heterozygous mutation in the SAMD9L gene (611170) on chromosome 7q21.</p><p>Heterozygous mutation in the SAMD9L gene can also cause monosomy 7 myelodysplasia and leukemia syndrome-1 (M7MLS1; 252270), which shows some overlapping features.</p>
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<strong>Description</strong>
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<p>Ataxia-pancytopenia syndrome (ATXPC) is an autosomal dominant disorder characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to bone marrow failure and myeloid leukemia. The germline genetic defect is associated with somatic loss of chromosome 7 (monosomy 7) resulting in the deletion of several genes on chromosome 7 that may predispose to the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) (summary by Chen et al., 2016 and Tesi et al., 2017). </p>
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<strong>Clinical Features</strong>
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<p>Li et al. (1978, 1981) described a family with ataxia and pancytopenia. The propositus, the youngest of a sibship of 5, had cerebellar ataxia, developed hypoplastic anemia at age 3 years, and died of acute myelomonocytic leukemia at age 7. Serial cytogenetic studies of his hypoplastic bone marrow over a 25-month period showed progressive expansion of a clone of cells with monosomy 7 (252270). Cerebellar ataxia was found in the proband's father and all 4 sibs. Two brothers, including 1 with monosomy 7, died with hypoplastic anemia at ages 5 and 9 years, and a third brother died with acute myelocytic leukemia at age 10 years. The only surviving sib at the time of the report of Li et al. (1981) was a 19-year-old sister who had unexplained anemia, decreased mitotic activity in the bone marrow, and a slowly progressive cerebellar ataxia. In addition to progressive cerebellar ataxia, the father had marked progressive cerebellar ataxia, brisk deep tendon reflexes, bilateral Babinski reflexes, and diminished vibratory sensation in the legs. Unsteady gait first brought the father to medical attention at age 28 years and he was not able to work thereafter. Computed tomographic scans of the father, the sister, and 1 brother showed cerebellar atrophy. Autopsy in 1 brother showed marked cerebellar atrophy and loss of 90% of the Purkinje cells; the spinal column was normal. By 1989, the sister had given up her career in nursing because of increasingly severe cerebellar ataxia and the father was largely confined at home (Li, 1989). </p><p>In a family reported by Daghistani et al. (1989), the proband, a 5-year-old boy, presented with left facial abscess and pancytopenia, following a 2-year history of mild incoordination. He had nystagmus and dysmetria. Monosomy 7 was found. He died at the age of about 6 years from pancytopenia. The sister of the proband, 12 years old at the time of report, had the onset of mild progressive unsteadiness at the age of 7 years. She had nystagmus and dysarthria. Nerve conduction studies showed reduced velocities in both sibs. The mother of the 2 children had had onset of incoordination before age 5. She showed severe gait ataxia and pronounced dysarthria with upper extremity dysmetria and horizontal and vertical nystagmus. Nerve conduction studies showed reduced velocities. The father was normal neurologically and hematologically. None of the 3 patients had oculocutaneous telangiectasia, scoliosis, or cardiac dysfunction. </p><p>Chen et al. (2016) reported a large multigenerational family (UW-AP) of German, Irish, and Native American descent in which at least 9 individuals had ataxia-pancytopenia syndrome. The phenotype was highly variable, with onset of symptoms ranging from 6 to 62 years of age, although manifestations could be detected earlier by examination. Neurologic features included gait imbalance, horizontal and vertical nystagmus, dysmetria, hyperreflexia, ankle clonus, and sometimes extensor plantar responses. Brain imaging, performed in 2 patients, showed cerebellar atrophy or degeneration. Hematologic abnormalities, which were variable and sometimes intermittent, included anemia, leukopenia, and thrombocytopenia. Four adult sibs were described in detail. The first patient presented with pancytopenia at age 3 months. Bone marrow aspirate at age 11 years showed hypoplasia with normal maturation and some immature forms. He developed slowly progressive balance issues at age 30, and by age 47, he had nystagmus, dysarthria, dysmetria, hyperreflexia, and normal gait but difficulty with tandem walking. His brother presented at age 1 year with thrombocytopenia that later evolved to pancytopenia. He developed a retroperitoneal bleed and died at age 16 years. He had no neurologic manifestations or ataxia, but postmortem examination showed cerebellar atrophy with severe loss of Purkinje cells and gliosis in the hippocampus. The third patient developed unsteady gait at age 25 that progressed to severe ataxia requiring a walker by age 38. Other features included severe dysarthria, nystagmus, and hyperreflexia. Laboratory studies showed mild leukopenia and mild to moderate thrombocytopenia. The fourth patient first noted balance problems at age 36, but physical examination at age 25 had shown nystagmus and ankle clonus. She developed intermittent mild neutropenia and thrombocytopenia after age 45. Chen et al. (2016) noted that the severities of the hematologic and neurologic abnormalities were not concordant in this family. None of the patients had dysplastic marrow changes and none developed myelodysplasia or leukemia. Patient cells showed normal DNA repair responses, no increased sensitivity to ionizing radiation, and normal telomere lengths. </p><p>Gonzalez-del Angel et al. (2000) described a Mexican girl who developed cerebellar ataxia at age 3 years and pancytopenia at age 13 years. Cerebral computed tomography scan and magnetic resonance imaging showed evidence of severe cerebellar atrophy. Telangiectases were not present, and immunoglobulins and alpha-fetoprotein levels were normal, making ataxia-telangiectasia (208900) unlikely. Cytogenetic studies showed no abnormalities except for an increased frequency of chromosomal aberrations in response to bleomycin. The phenotype was considered consistent with the ataxia-pancytopenia syndrome, although monosomy of chromosome 7 was not found in bone marrow. The sensitivity to bleomycin suggested this may be a chromosomal instability disorder. </p><p>Tesi et al. (2017) reported 2 unrelated families of Swedish and Finnish origin, respectively, with a syndromic disorder characterized by hematologic and neurologic dysfunction. The proband in the first family was a 4-year-old boy with a history of CMV infection, trilineage cytopenia, hypogammaglobulinemia, and MDS associated with monosomy 7. He underwent successful hematopoietic stem cell transplantation and thereafter developed neurologic symptoms, including nystagmus, unsteady gait, and lower limb stiffness and weakness. Brain imaging showed white matter abnormalities and progressive cerebellar degeneration. His grandfather developed MDS at age 56 years and did not have monosomy 7. He had mildly impaired balance. None of the other affected family members had MDS, but several had transient thrombocytopenia or pancytopenia, often associated with uniparental disomy of chromosome 7q or a revertant SAMD9L variant. Most, but not all, patients had mild neurologic symptoms, mainly nystagmus and impaired balance. In the second family, a mother and her 2 affected children had recurrent infections suggesting mild immunodeficiency. They also had variable neurologic features, such as nystagmus, balance problems, and attention deficit-hyperactivity disorder. The 2 children had thrombocytopenia and pancytopenia, one with a hypoplastic bone marrow and the other with dysplastic megakaryocytes and MDS. Although both of these patients had uniparental disomy of 7q, only 1 had monosomy 7; the latter patient underwent hematopoietic stem cell transplantation. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of ATXPC in the families reported by Li et al. (1978) and Chen et al. (2016) was consistent with autosomal dominant inheritance. </p><p>The transmission pattern of ATXPC in the families reported by Tesi et al. (2017) was consistent with autosomal dominant inheritance with incomplete penetrance and variable expressivity. </p>
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<strong>Molecular Genetics</strong>
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<p>In affected members of 2 unrelated families with ATXPC, including the family originally reported by Li et al. (1978), Chen et al. (2016) identified 2 different heterozygous missense mutations in the SAMD9L gene (H880Q, 611170.0001 and C1196S, 611170.0002). The mutation in the first family was found by a combination of linkage analysis and exome sequencing. Functional studies of the variants were not performed. </p><p>In affected members of 2 unrelated families with ATXPC, Tesi et al. (2017) identified germline heterozygous gain-of-function mutations in the SAMD9L gene (R986C, 611170.0003 and I891T, 611170.0004). The mutations, which were found by whole-exome or Sanger sequencing, segregated with the disorder in the family, although there was variable expressivity. In vitro functional expression studies in cells transfected with the mutations showed that they augmented the growth-suppressing activity of SAMD9L and halted cell proliferation compared to wildtype, consistent with a gain-of-function effect. Some patients developed MDS associated with monosomy 7; loss of chromosome 7 in these patients eliminated the SAMD9L mutations, suggesting that the SAMD9L mutations were not themselves conducive to tumor cell propagation, but that cytogenetic events eradicating the chromosome may explain the predisposition to MDS. This would be an example of 'adaptation by aneuploidy.' In contrast, other family members had less severe or limited manifestations associated with uniparental disomy of 7q or revertant SAMD9L mosaicism that likely mitigated the pathogenic effects of the familial mutations by acting as loss-of-function alleles. In in vitro studies, Tesi et al. (2017) found that stimulation of CD34+ hematopoietic stem cells with IFNA (147660) or IFNG (147570) induced SAMD9L expression. These findings provided a mechanism by which an immune response may indirectly lead to cytopenia, thus providing a basis for the selection of somatic SAMD9L revertant mutants. </p>
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<strong>REFERENCES</strong>
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Chen, D.-H., Below, J. E., Shimamura, A., Keel, S. B., Matsushita, M., Wolff, J., Sul, Y., Bonkowski, E., Castella, M., Taniguchi, T., Nickerson, D., Papayannopoulou, T., Bird, T. D., Raskind, W. H.
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<strong>Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L.</strong>
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Am. J. Hum. Genet. 98: 1146-1158, 2016.
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[PubMed: 27259050]
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[Full Text: https://doi.org/10.1016/j.ajhg.2016.04.009]
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Daghistani, D., Curless, R., Toledano, S. R., Ayyar, D. R.
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<strong>Ataxia-pancytopenia and monosomy 7 syndrome.</strong>
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J. Pediat. 115: 108-110, 1989.
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[PubMed: 2738778]
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[Full Text: https://doi.org/10.1016/s0022-3476(89)80342-7]
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<li>
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Gonzalez-del Angel, A., Cervera, M., Gomez, L., Perez-Vera, P., Orozco, L., Carnevale, A., Del Castillo, V.
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<strong>Ataxia-pancytopenia syndrome.</strong>
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Am. J. Med. Genet. 90: 252-254, 2000.
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[PubMed: 10678666]
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[Full Text: https://doi.org/10.1002/(sici)1096-8628(20000131)90:3<252::aid-ajmg14>3.3.co;2-m]
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<p class="mim-text-font">
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Li, F. P., Hecht, F., Kaiser-McCaw, B., Baranko, P. V., Potter, N. U.
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<strong>Ataxia-pancytopenia: syndrome of cerebellar ataxia, hypoplastic anemia, monosomy 7, and acute myelogenous leukemia.</strong>
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Cancer Genet. Cytogenet. 4: 189-196, 1981.
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[PubMed: 6947857]
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[Full Text: https://doi.org/10.1016/0165-4608(81)90013-3]
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<li>
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<p class="mim-text-font">
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Li, F. P., Potter, N. U., Buchanan, G. R., Vawter, G., Whang-Peng, J., Rosen, R. B.
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<strong>A family with acute leukemia, hypoplastic anemia and cerebellar ataxia: association with bone marrow C-monosomy.</strong>
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Am. J. Med. 65: 933-940, 1978.
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[PubMed: 283689]
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[Full Text: https://doi.org/10.1016/0002-9343(78)90744-1]
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<p class="mim-text-font">
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Li, F. P.
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<strong>Personal Communication.</strong>
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Boston, Mass. 10/3/1989.
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<p class="mim-text-font">
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Tesi, B., Davidsson, J., Voss, M., Rahikkala, E., Holmes, T. D., Chiang, S. C. C., Komulainen-Ebrahim, J., Gorcenco, S., Nilsson, A. R., Ripperger, T., Kokkonen, H., Bryder, D., and 13 others.
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<strong>Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms.</strong>
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Blood 129: 2266-2279, 2017.
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[PubMed: 28202457]
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[Full Text: https://doi.org/10.1182/blood-2016-10-743302]
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 12/07/2020<br>Cassandra L. Kniffin - updated : 6/22/2016<br>Cassandra L. Kniffin - updated : 12/30/2008<br>Victor A. McKusick - updated : 2/24/2000
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Victor A. McKusick : 6/2/1986
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carol : 12/10/2020<br>ckniffin : 12/07/2020<br>alopez : 01/02/2019<br>joanna : 07/01/2016<br>alopez : 6/30/2016<br>ckniffin : 6/22/2016<br>joanna : 7/20/2012<br>wwang : 1/15/2009<br>wwang : 1/15/2009<br>ckniffin : 12/30/2008<br>carol : 4/2/2001<br>terry : 2/24/2000<br>mimadm : 12/2/1994<br>davew : 7/14/1994<br>warfield : 4/21/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>carol : 12/9/1989
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