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<title>
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Entry
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- #252270 - MONOSOMY 7 MYELODYSPLASIA AND LEUKEMIA SYNDROME 1; M7MLS1
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- OMIM
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<span class="h4">#252270</span>
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<strong>Table of Contents</strong>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/phenotypicSeries/PS252270"> <strong>Phenotypic Series</strong> </a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<a href="#cytogenetics">Cytogenetics</a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(MONOSOMY 7 MYELODYSPLASIA LEUKEMIA SYNDROME) OR (SAMD9L)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=25813&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://medlineplus.gov/genetics/condition/ataxia-pancytopenia-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=252270[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=495930" 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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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 495930<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
|
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252270
|
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
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MONOSOMY 7 MYELODYSPLASIA AND LEUKEMIA SYNDROME 1; M7MLS1
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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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MLSM7<br />
|
|
MONOSOMY 7 OF BONE MARROW<br />
|
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CHROMOSOME 7q DELETION
|
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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">
|
|
<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">
|
|
7q21.2
|
|
</a>
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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Monosomy 7 myelodysplasia and leukemia syndrome 1
|
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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/252270"> 252270 </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>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
SAMD9L
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
<a href="/entry/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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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/252270" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
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|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
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</div>
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<div class="btn-group">
|
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|
|
<a href="/phenotypicSeries/PS252270" class="btn btn-info" role="button"> Phenotypic Series </a>
|
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|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
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<span class="sr-only">Toggle Dropdown</span>
|
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</button>
|
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</div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/252270" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/252270" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
|
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<p />
|
|
</div>
|
|
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|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
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<div>
|
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
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|
|
</div>
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spleen </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Splenomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16294009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16294009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038002</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
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|
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|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEMATOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Anemia <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 /> -
|
|
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 /> -
|
|
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 /> -
|
|
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 /> -
|
|
Erythrocyte macrocytosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/165454002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">165454002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0302845&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0302845</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005518</a>]</span><br /> -
|
|
Hypocellular bone marrow <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/416995001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">416995001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/307762000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">307762000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D61.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D61.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151773&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151773</a>]</span><br /> -
|
|
Dyspoiesis in bone marrow <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435706&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435706</a>]</span><br /> -
|
|
Dysplastic bone marrow <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4540466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4540466</a>]</span><br /> -
|
|
Myelodysplastic syndrome <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">
|
|
<strong> IMMUNOLOGY </strong>
|
|
</span>
|
|
</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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|
|
- Immunodeficiency, mild (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435705&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435705</a>]</span> <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">[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 /> -
|
|
Recurrent infections (in some patients) <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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</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">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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|
|
- Acute myelogenous leukemia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91861009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91861009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1162928000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1162928000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C92.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C92.00</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/C92.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C92.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/205.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">205.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023467&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023467</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004808</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004808</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">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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|
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<div>
|
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<span class="mim-font">
|
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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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</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> MISCELLANEOUS </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
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|
|
- Onset usually in early childhood<br /> -
|
|
Highly variable phenotype and severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850667&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850667</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br /> -
|
|
Incomplete penetrance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836598&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836598</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</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">
|
|
<strong> MOLECULAR BASIS </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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|
|
- 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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</span>
|
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</div>
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</div>
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</div>
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<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
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</div>
|
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</div>
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</div>
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|
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<div class="small">
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<div class="row">
|
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Monosomy 7 myelodysplasia and leukemia syndrome
|
|
- <a href="/phenotypicSeries/PS252270">PS252270</a>
|
|
- 2 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
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|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
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<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
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<thead>
|
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<tr>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Location</strong>
|
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</th>
|
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
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<strong>Phenotype</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Inheritance</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />mapping key</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
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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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|
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<a href="/geneMap/7/413?start=-3&limit=10&highlight=413"> 7q21.2 </a>
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|
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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/619041"> Monosomy 7 myelodysplasia and leukemia syndrome 2 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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|
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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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|
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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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|
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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/619041"> 619041 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/610456"> SAMD9 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610456"> 610456 </a>
|
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</span>
|
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</td>
|
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</tr>
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<tr>
|
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<td>
|
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<span class="mim-font">
|
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|
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<a href="/geneMap/7/414?start=-3&limit=10&highlight=414"> 7q21.2 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/252270"> Monosomy 7 myelodysplasia and leukemia syndrome 1 </a>
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<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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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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<a href="/entry/252270"> 252270 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/611170"> SAMD9L </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/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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</table>
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</div>
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<div class="text-right small">
|
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
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</div>
|
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that monosomy 7 myelodysplasia and leukemia syndrome-1 (M7MLS1) is caused by heterozygous germline mutation in the SAMD9L gene (<a href="/entry/611170">611170</a>) on chromosome 7q21. This germline genetic defect is associated with somatic loss of chromosome 7, resulting in the deletion of several genes that may predispose to the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). One putative candidate gene is EZH2 (<a href="/entry/601573">601573</a>).</p><p>Heterozygous mutation in the SAMD9L gene can also cause ataxia-pancytopenia syndrome (ATXPC; <a href="/entry/159550">159550</a>), which shows some overlapping features.</p>
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</span>
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<div>
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<br />
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</div>
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<p>Monosomy 7 myelodysplasia and leukemia syndrome-1 (M7MLS1) is an autosomal dominant hematologic disorder with highly variable manifestations. Most patients present in early childhood with pancytopenia and dyspoietic or dysplastic changes in the bone marrow. These abnormalities are almost always associated with monosomy 7 in the bone marrow. In severely affected individuals, the phenotype progresses to frank myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Less severely affected individuals may have transient thrombocytopenia or anemia, or have normal peripheral blood counts with transient bone marrow abnormalities or transient monosomy 7. Germline mutations in the SAMD9L gene, located on chromosome 7q, have a gain-of-function suppressive effect on the cell cycle, resulting in decreased cellular proliferation. It is hypothesized that this germline defect leads to selective pressure favoring somatic loss of the chromosome 7 harboring the mutant allele (adaptation by aneuploidy) (summary by <a href="#18" class="mim-tip-reference" title="Wong, J. C., Bryant, V., Lamprecht, T., Ma, J., Walsh, M., Schwartz, J., del pilar Alzamora, M., Mullighan C. G., Loh, M. L., Ribeiro, R., Downing, J. R., Carroll, W. L., Davis, J., Gold, S., Rogers, R. C., Israels S., Yanofsky, R., Shannon K., Klco, J. M. <strong>Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes.</strong> JCI Insight 3: 121086, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30046003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30046003</a>] [<a href="https://doi.org/10.1172/jci.insight.121086" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30046003">Wong et al., 2018</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30046003" 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>Monosomy 7 or partial deletion of the long arm of chromosome 7 (7q-) is a frequent cytogenetic finding in the bone marrow of patients with myelodysplasia and acute myelogenous leukemia. Furthermore, monosomy 7 or 7q- is the most frequent abnormality of karyotype in cases of AML that occur after cytotoxic cancer therapy or occupational exposure to mutagens. The age distribution of de novo cases shows peaks in the first and fifth decades. Monosomy 7 is found in about 5% of de novo and 40% of secondary cases of AML. These findings suggest that loss of certain genes at this region is an important event in the development of myelodysplasia (summary by <a href="#16" class="mim-tip-reference" title="Shannon, K. M., Turhan, A. G., Chang, S. S. Y., Bowcock, A. M., Rogers, P. C. J., Carroll, W. L., Cowan, M. J., Glader, B. E., Eaves, C. J., Eaves, A. C., Kan, Y. W. <strong>Familial bone marrow monosomy 7: evidence that the predisposing locus is not on the long arm of chromosome 7.</strong> J. Clin. Invest. 84: 984-989, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569483</a>] [<a href="https://doi.org/10.1172/JCI114262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2569483">Shannon et al., 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2569483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity of Monosomy 7 Myelodysplastic and Leukemia Syndrome</em></strong></p><p>
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See also M7MLS2 (<a href="/entry/619041">619041</a>), caused by germline mutation in the SAMD9 gene (<a href="/entry/610457">610457</a>) on chromosome 7q21.</p>
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<p><a href="#16" class="mim-tip-reference" title="Shannon, K. M., Turhan, A. G., Chang, S. S. Y., Bowcock, A. M., Rogers, P. C. J., Carroll, W. L., Cowan, M. J., Glader, B. E., Eaves, C. J., Eaves, A. C., Kan, Y. W. <strong>Familial bone marrow monosomy 7: evidence that the predisposing locus is not on the long arm of chromosome 7.</strong> J. Clin. Invest. 84: 984-989, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569483</a>] [<a href="https://doi.org/10.1172/JCI114262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2569483">Shannon et al. (1989)</a> studied 3 unrelated families, each with 2 patients who had MDS or AML associated with monosomy 7 in the bone marrow. The proband in the first family was a 6-year-old girl with AML and bone marrow monosomy 7. Her 5-year-old brother, who shared HLA antigens, was found during evaluation for donation of bone marrow to have mild thrombocytopenia, erythrocyte macrocytosis, and a minor subpopulation of bone marrow cells with monosomy 7. He went on to develop AML. Family 2 had 2 sisters, aged 16 and 17 years, with myelodysplasia and monosomy 7. In family 3, 2 affected brothers with a similar disorder were later found by <a href="#18" class="mim-tip-reference" title="Wong, J. C., Bryant, V., Lamprecht, T., Ma, J., Walsh, M., Schwartz, J., del pilar Alzamora, M., Mullighan C. G., Loh, M. L., Ribeiro, R., Downing, J. R., Carroll, W. L., Davis, J., Gold, S., Rogers, R. C., Israels S., Yanofsky, R., Shannon K., Klco, J. M. <strong>Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes.</strong> JCI Insight 3: 121086, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30046003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30046003</a>] [<a href="https://doi.org/10.1172/jci.insight.121086" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30046003">Wong et al. (2018)</a> to have a mutation in the SAMD9 gene, consistent with M7MLS2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2569483+30046003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Gilchrist, D. M., Friedman, J. M., Rogers, P. C. J., Creighton, S. P. <strong>Myelodysplasia and leukemia syndrome with monosomy 7: a genetic perspective.</strong> Am. J. Med. Genet. 35: 437-441, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309795</a>] [<a href="https://doi.org/10.1002/ajmg.1320350323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2309795">Gilchrist et al. (1990)</a> described 2 brothers, aged 3 and 5 years, with M7MLS. Since bone marrow transplantation is the only effective treatment of M7MLS, the authors noted that familial occurrence should be kept in mind when searching for a donor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2309795" 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="Kwong, Y. L., Ng, M. H., Ma, S. K. <strong>Familial acute myeloid leukemia with monosomy 7: late onset and involvement of a multipotential progenitor cell.</strong> Cancer Genet. Cytogenet. 116: 170-173, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10640152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10640152</a>] [<a href="https://doi.org/10.1016/s0165-4608(99)00121-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10640152">Kwong et al. (2000)</a> described a family with 3 sibs affected by AML in whom monosomy 7 was demonstrated. The family showed several unusual features, including the late onset of AML (34 and 37 years of age in 2 of the sibs) and the presence of an antecedent myelodysplastic phase before leukemia developed. By fluorescence in situ hybridization, the monosomy 7 clone was shown to be capable of partial maturation, which was consistent with the biologic behavior of myelodysplasia. They pointed to the earlier report of <a href="#11" class="mim-tip-reference" title="Mitelman, F., Heim, S. <strong>Quantitative acute leukemia cytogenetics.</strong> Genes Chromosomes Cancer 5: 57-66, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1384663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1384663</a>] [<a href="https://doi.org/10.1002/gcc.2870050109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1384663">Mitelman and Heim (1992)</a>, and the reports of familial cases by <a href="#8" class="mim-tip-reference" title="Larsen, W. E., Schimke, R. N. <strong>Familial acute myelogenous leukemia with associated C-monosomy in two affected members.</strong> Cancer 38: 841-845, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1067893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1067893</a>] [<a href="https://doi.org/10.1002/1097-0142(197608)38:2<841::aid-cncr2820380230>3.0.co;2-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1067893">Larsen and Schimke (1976)</a>, <a href="#3" class="mim-tip-reference" title="Chitambar, C. R., Robinson, W. A., Glode, L. M. <strong>Familial leukemia and aplastic anemia associated with monosomy 7.</strong> Am. J. Med. 75: 756-762, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6638045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6638045</a>] [<a href="https://doi.org/10.1016/0002-9343(83)90404-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6638045">Chitambar et al. (1983)</a>, <a href="#2" class="mim-tip-reference" title="Carroll, W. L., Morgan, R., Glader, B. E. <strong>Childhood bone marrow monosomy 7 syndrome: a familial disorder?</strong> J. Pediat. 107: 578-580, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3862804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3862804</a>] [<a href="https://doi.org/10.1016/s0022-3476(85)80027-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3862804">Carroll et al. (1985)</a>, and <a href="#14" class="mim-tip-reference" title="Paul, B., Reid, M. M., Davison, E. V., Abela, M., Hamilton, P. J. <strong>Familial myelodysplasia: progressive disease associated with emergence of monosomy 7.</strong> Brit. J. Haemat. 65: 321-323, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3567084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3567084</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1987.tb06860.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3567084">Paul et al. (1987)</a>, among others. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10640152+1067893+6638045+1384663+3567084+3862804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Minelli, A., Maserati, E., Giudici, G., Tosi, S., Olivieri, C., Bonvini, L., De Filippi, P., Biondi, A., Lo Curto, F., Pasquali, F., Danesino, C. <strong>Familial partial monosomy 7 and myelodysplasia: different parental origin of the monosomy 7 suggests action of a mutator gene.</strong> Cancer Genet. Cytogenet. 124: 147-151, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11172908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11172908</a>] [<a href="https://doi.org/10.1016/s0165-4608(00)00344-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11172908">Minelli et al. (2001)</a> described 2 sisters with a myelodysplastic syndrome associated with partial monosomy 7. Trisomy 8 was also present in 1 of the sisters, who later developed acute myeloid leukemia of the M0 FAB-type and died, whereas the other sister died with no evolution into AML. The authors found that the parental origin of the deleted chromosome 7 was different in the 2 sisters, thus confirming that familial monosomy 7 is not explained by a germline mutation of a possible tumor suppressor gene. Similar results were obtained in 2 other families of the 12 reported in the literature. Noteworthy was the association with a mendelian disorder in 3 of the 12 monosomy 7 families, which suggested that a mutator gene, capable of inducing both karyotype instability and a mendelian disorder, may act to induce chromosome 7 anomalies in the marrow. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11172908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Wong, J. C., Bryant, V., Lamprecht, T., Ma, J., Walsh, M., Schwartz, J., del pilar Alzamora, M., Mullighan C. G., Loh, M. L., Ribeiro, R., Downing, J. R., Carroll, W. L., Davis, J., Gold, S., Rogers, R. C., Israels S., Yanofsky, R., Shannon K., Klco, J. M. <strong>Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes.</strong> JCI Insight 3: 121086, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30046003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30046003</a>] [<a href="https://doi.org/10.1172/jci.insight.121086" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30046003">Wong et al. (2018)</a> reported 4 unrelated families with variable manifestations of M7MLS1 associated with heterozygous germline missense mutations in the SAMD9L gene (see MOLECULAR GENETICS). Two sibs in the first family presented with AML in childhood. Bone marrow examination of both sibs showed deletion of the paternal copy of chromosome 7, yielding monosomy 7. Deep sequencing showed that the SAMD9L gene was present at a low frequency (less than 5%) in the bone marrow of both children, indicating selective loss of the chromosome harboring the SAMD9L mutation. Leukemic cells in both affected sibs showed acquisition of somatic mutations in other genes, including RUNX1 (<a href="/entry/151385">151385</a>), SETBP1 (<a href="/entry/611060">611060</a>), BRAF (<a href="/entry/164757">164757</a>), and KRAS (<a href="/entry/164757">164757</a>), which likely contributed to leukemogenesis. Both patients died. The family had previously been reported as family 1 by <a href="#16" class="mim-tip-reference" title="Shannon, K. M., Turhan, A. G., Chang, S. S. Y., Bowcock, A. M., Rogers, P. C. J., Carroll, W. L., Cowan, M. J., Glader, B. E., Eaves, C. J., Eaves, A. C., Kan, Y. W. <strong>Familial bone marrow monosomy 7: evidence that the predisposing locus is not on the long arm of chromosome 7.</strong> J. Clin. Invest. 84: 984-989, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569483</a>] [<a href="https://doi.org/10.1172/JCI114262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2569483">Shannon et al. (1989)</a>. Three other affected families (families 3, 4, and 5) had a less severe phenotype. The proband in family 3 presented in early childhood with MDS and monosomy 7. She underwent successful bone marrow transplant and was well at age 27 years. Genetic studies of her sister, who had no overt hematologic abnormalities, detected a focal somatic deletion of 7q11-q36 that contained the SAMD9L gene in 7 of 27 metaphase cells. She died of an unrelated cause at age 27 years. The proband in family 4 presented at 3 years of age with pneumonia, oral candidiasis, pancytopenia, and monosomy 7 in bone marrow metaphase cells. She was treated successfully with antibiotics and her blood counts recovered. At age 7 years, cytogenetic analysis of her bone marrow was normal. Her 1.5-year-old sister was in good health with normal peripheral blood counts, although bone marrow showed monosomy 7 in 9 of 10 metaphase cells. By age 4, her bone marrow cytogenetics were normal. These patients were alive and well at 19 and 21 years of age. Eight sibs from family 5, who ranged in age from 8 to 26 years, had variable hematologic abnormalities, including anemia, cytopenia, neutropenia, and hypocellular bone marrow with dysplastic changes. None developed MDS or AML. Four patients had transient monosomy 7 in bone marrow cells that resolved over time without treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2569483+30046003" 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 M7MLS1 in the families reported by <a href="#18" class="mim-tip-reference" title="Wong, J. C., Bryant, V., Lamprecht, T., Ma, J., Walsh, M., Schwartz, J., del pilar Alzamora, M., Mullighan C. G., Loh, M. L., Ribeiro, R., Downing, J. R., Carroll, W. L., Davis, J., Gold, S., Rogers, R. C., Israels S., Yanofsky, R., Shannon K., Klco, J. M. <strong>Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes.</strong> JCI Insight 3: 121086, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30046003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30046003</a>] [<a href="https://doi.org/10.1172/jci.insight.121086" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30046003">Wong et al. (2018)</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=30046003" 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>Reasoning along the lines of the Knudson model of oncogenesis, <a href="#16" class="mim-tip-reference" title="Shannon, K. M., Turhan, A. G., Chang, S. S. Y., Bowcock, A. M., Rogers, P. C. J., Carroll, W. L., Cowan, M. J., Glader, B. E., Eaves, C. J., Eaves, A. C., Kan, Y. W. <strong>Familial bone marrow monosomy 7: evidence that the predisposing locus is not on the long arm of chromosome 7.</strong> J. Clin. Invest. 84: 984-989, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2569483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2569483</a>] [<a href="https://doi.org/10.1172/JCI114262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2569483">Shannon et al. (1989)</a> used probes that mapped to chromosome 7q22-q34 to investigate 3 families with monosomy 7. It was demonstrated that different parental chromosomes 7 were retained in the leukemic bone marrows of the sibs of these families; thus, a familial predisposition to myelodysplasia could not be located within the consistently deleted segment. In the first family studied, markers on proximal 7q showed that the leukemic chromosome 7 came from the mother in both sibs, but in 1 sib a somatic recombination had occurred, resulting in paternal derivation of the distal part of 7q in leukemic cells. In further studies of 3 pairs of sibs, <a href="#17" class="mim-tip-reference" title="Shannon, K. M., Turhan, A. G., Rogers, P. C. J., Kan, Y. W. <strong>Evidence implicating heterozygous deletion of chromosome 7 in the pathogenesis of familial leukemia associated with monosomy 7.</strong> Genomics 14: 121-125, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1358790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1358790</a>] [<a href="https://doi.org/10.1016/s0888-7543(05)80293-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1358790">Shannon et al. (1992)</a> found no overlapping region where all 3 pairs retained DNA derived from the same paternal or maternal chromosome, suggesting that there may not be a familial disposition to the disorder resulting from germline events. However, the findings suggested that there may be multiple somatic events involving 7q in the pathogenesis of myelodysplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2569483+1358790" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using microarray-based comparative genomic hybridization (CGH) analysis, <a href="#1" class="mim-tip-reference" title="Asou, H., Matsui, H., Ozaki, Y., Nagamachi, A., Nakamura, M., Aki, D., Inaba, T. <strong>Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome.</strong> Biochem. Biophys. Res. Commun. 383: 245-251, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19358830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19358830</a>] [<a href="https://doi.org/10.1016/j.bbrc.2009.04.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19358830">Asou et al. (2009)</a> identified a common microdeletion involving chromosome 7q21.2-q21.3 in 8 of 21 patients with juvenile myelomonocytic leukemia and normal karyotype. The microdeletion was verified by quantitative PCR analysis and involved 3 contiguous genes, SAMD9, SAMD9L, and HEPACAM2 (<a href="/entry/614133">614133</a>). These 3 genes were heterozygously deleted at high frequency in both adult and childhood myeloid leukemia and were commonly lost with larger deletions of chromosome 7 in 15 of 61 adult MDS/AML patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19358830" 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="#13" class="mim-tip-reference" title="Nikoloski, G., Langemeijer, S. M. C., Kuiper, R. P., Knops, R., Massop, M., Tonnissen, E. R. L. T. M., van der Heijden, A., Scheele, T. N., Vandenberghe, P., de Witte, T., van der Reijden, B. A., Jansen, J. H. <strong>Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes.</strong> Nature Genet. 42: 665-667, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20601954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20601954</a>] [<a href="https://doi.org/10.1038/ng.620" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20601954">Nikoloski et al. (2010)</a> identified heterozygous acquired (somatic) deletions at chromosome 7q36.1 encompassing the EZH2 (<a href="/entry/601573">601573</a>) and CUL1 (<a href="/entry/603134">603134</a>) genes in bone marrow cells derived from 13 of 102 individuals with myelodysplastic syndromes, including refractory anemia (RA). Two additional affected individuals had uniparental disomy (UPD) of this region. Genomic analysis of the remaining allele in 1 patient showed no aberrations in CUL1, but a truncating mutation in EZH2. Further sequencing of the EZH2 gene identified somatic mutations in 8 (26%) of 126 individuals, including the original 102 individuals. Three individuals had biallelic mutations. Collectively, 23% of affected individuals had deletions and/or point mutations in the EZH2 gene, and 40% of these individuals also had defects in the TET2 gene (<a href="/entry/612839">612839</a>). Individuals with defects at chromosome 7q showed significantly worse survival compared to those without these defects. The findings suggested that EZH2 may act as a tumor suppressor gene in some cases, and likely influences epigenetic modifications that may lead to cancer, since EZH2 functions as a histone methyltransferase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20601954" 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="#5" class="mim-tip-reference" title="Ernst, T., Chase, A. J., Score, J., Hidalgo-Curtis, C. E., Bryant, C., Jones, A. V., Waghorn, K., Zoi, K., Ross, F. M., Reiter, A., Hochhaus, A., Drexler, H. G., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F. H., Cross, N. C. <strong>Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.</strong> Nature Genet. 42: 722-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20601953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20601953</a>] [<a href="https://doi.org/10.1038/ng.621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20601953">Ernst et al. (2010)</a> found that 9 of 12 individuals with myelodysplastic/myeloproliferative neoplasms and acquired UPD encompassing chromosome 7q36 also had a homozygous EZH2 mutation. Further sequencing of 614 individuals with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals; the mutations were found most commonly in those with myelodysplastic/myeloproliferative neoplasms (27 of 219, 12%) and in those with myelofibrosis (4 of 30, 13%). Several patients had refractory anemia, suggesting that somatic acquisition of these abnormalities may be an early event in the disease process. The mutations identified resulted in premature chain termination or direct abrogation of histone methyltransferase activity, suggesting that EZH2 can act as a tumor suppressor for myeloid malignancies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20601953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Makishima, H., Jankowska, A. M., Tiu, R. V., Szpurka, H., Sugimoto, Y., Hu, Z., Saunthararajah, Y., Guinta, K., Keddache, M. A., Putnam, P., Sekeres, M. A., Moliterno, A. R., List, A. F., McDevitt, M. A., Maciejewski, J. P. <strong>Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies.</strong> Leukemia 24: 1799-1804, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20724984/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20724984</a>] [<a href="https://doi.org/10.1038/leu.2010.167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20724984">Makishima et al. (2010)</a> analyzed the EZH2 gene in 344 patients with myeloid malignancies, of whom 15 had UDP7q, 30 had del(7q), and 299 had no loss of heterozygosity of chromosome 7. They found 4 different EZH2 mutations in 3 (20%) of 15 patients with UDP7q and in 2 (7%) of 30 patients with del(7q); in 1 patient without LOH7q, a heterozygous frameshift mutation was identified. All were somatic mutations located in exon 18 or 19, coding for the SET domain of the EZH2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20724984" 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 4 unrelated families (families 1, 3, 4, and 5) with variable manifestations of M7MLS1, <a href="#18" class="mim-tip-reference" title="Wong, J. C., Bryant, V., Lamprecht, T., Ma, J., Walsh, M., Schwartz, J., del pilar Alzamora, M., Mullighan C. G., Loh, M. L., Ribeiro, R., Downing, J. R., Carroll, W. L., Davis, J., Gold, S., Rogers, R. C., Israels S., Yanofsky, R., Shannon K., Klco, J. M. <strong>Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes.</strong> JCI Insight 3: 121086, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30046003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30046003</a>] [<a href="https://doi.org/10.1172/jci.insight.121086" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30046003">Wong et al. (2018)</a> identified heterozygous missense mutations in the SAMD9L gene (<a href="/entry/611170#0001">611170.0001</a>; <a href="/entry/611170#0003">611170.0003</a>; <a href="/entry/611170#0005">611170.0005</a>-<a href="/entry/611170#0006">611170.0006</a>). The mutations, which were filtered against public databases, segregated with the disorders in the families. In vitro functional expression studies in HEK293T cells transfected with the mutations showed that they suppressed cell cycle progression and impaired cellular growth and proliferation stronger than wildtype, consistent with a gain-of-function effect. Most patients had monosomy 7, although the phenotype was variable. The sibs in family 1 had AML, ultimately resulting in early death, whereas the patients in families 3-5 had milder hematologic abnormalities and long survival. In contrast to the patients in family 1, none of the patients in families 3, 4, or 5 had somatic mutations in genes associated with the development of MDS or AML. In addition, several patients in families 3-5 had resolution of monosomy 7 without treatment, and most had additional acquired variants in the SAMD9L gene that were demonstrated or predicted to mitigate the effects of the pathogenic germline mutation. The findings emphasized the phenotypic heterogeneity in this disorder resulting from complex genetic mechanisms, including germline mutation, monosomy 7, acquired SAMD9L revertant variants, and acquired somatic changes in additional genes associated with the development of MDS or AML. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30046003" 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 occurrence of mosaicism for trisomy 7 in normal tissues (kidney, liver, brain), as found by <a href="#12" class="mim-tip-reference" title="Mittelman, F. <strong>Personal Communication.</strong> Lund, Sweden 9/22/1989."None>Mittelman (1989)</a>, is noteworthy, as is the occurrence of uniparental disomy involving chromosome 7 and leading to cystic fibrosis (see <a href="/entry/219700">219700</a>).</p><p><a href="#15" class="mim-tip-reference" title="Ruutu, P., Ruutu, T., Vuopio, P., Kosunen, T. U., de la Chapelle, A. <strong>Defective chemotaxis in monosomy-7.</strong> Nature 265: 146-147, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/264599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">264599</a>] [<a href="https://doi.org/10.1038/265146a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="264599">Ruutu et al. (1977)</a> found an association between monosomy 7 and defective chemotaxis, suggesting that a gene for normal chemotactic or chemokinetic response of neutrophils may be located on that chromosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=264599" 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="#4" class="mim-tip-reference" title="de la Chapelle, A., Ruutu, P., Ruutu, T., Repo, H., Vuopio, P., Timonen, T., Kosunen, T. U. <strong>The locomotion defect of granulocytes in monosomy 7 involves random locomotion, chemotaxis and chemokinesis. (Abstract)</strong> Cytogenet. Cell Genet. 32: 264-265, 1982."None>De la Chapelle et al. (1982)</a> reported that the locomotion defect of granulocytes in monosomy 7 involves random locomotion, chemotaxis, and chemokinesis.</p>
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Asou, H., Matsui, H., Ozaki, Y., Nagamachi, A., Nakamura, M., Aki, D., Inaba, T.
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<strong>Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome.</strong>
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Biochem. Biophys. Res. Commun. 383: 245-251, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19358830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19358830</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19358830" 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.bbrc.2009.04.004" target="_blank">Full Text</a>]
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Carroll, W. L., Morgan, R., Glader, B. E.
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<strong>Childhood bone marrow monosomy 7 syndrome: a familial disorder?</strong>
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J. Pediat. 107: 578-580, 1985.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3862804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3862804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3862804" 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(85)80027-5" target="_blank">Full Text</a>]
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Chitambar, C. R., Robinson, W. A., Glode, L. M.
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<strong>Familial leukemia and aplastic anemia associated with monosomy 7.</strong>
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Am. J. Med. 75: 756-762, 1983.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6638045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6638045</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6638045" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0002-9343(83)90404-7" target="_blank">Full Text</a>]
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de la Chapelle, A., Ruutu, P., Ruutu, T., Repo, H., Vuopio, P., Timonen, T., Kosunen, T. U.
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<strong>The locomotion defect of granulocytes in monosomy 7 involves random locomotion, chemotaxis and chemokinesis. (Abstract)</strong>
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Cytogenet. Cell Genet. 32: 264-265, 1982.
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Ernst, T., Chase, A. J., Score, J., Hidalgo-Curtis, C. E., Bryant, C., Jones, A. V., Waghorn, K., Zoi, K., Ross, F. M., Reiter, A., Hochhaus, A., Drexler, H. G., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F. H., Cross, N. C.
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<strong>Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.</strong>
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Nature Genet. 42: 722-726, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20601953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20601953</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20601953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/leu.2010.167" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ng.620" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/265146a0" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI114262" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0888-7543(05)80293-9" target="_blank">Full Text</a>]
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Wong, J. C., Bryant, V., Lamprecht, T., Ma, J., Walsh, M., Schwartz, J., del pilar Alzamora, M., Mullighan C. G., Loh, M. L., Ribeiro, R., Downing, J. R., Carroll, W. L., Davis, J., Gold, S., Rogers, R. C., Israels S., Yanofsky, R., Shannon K., Klco, J. M.
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Cassandra L. Kniffin - updated : 12/07/2020
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Marla J. F. O'Neill - updated : 1/10/2012<br>Patricia A. Hartz - updated : 8/4/2011<br>Cassandra L. Kniffin - updated : 11/18/2010<br>Victor A. McKusick - updated : 4/12/2001<br>Victor A. McKusick - updated : 3/15/2000
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Victor A. McKusick : 10/4/1989
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carol : 12/14/2020<br>carol : 12/11/2020<br>carol : 12/10/2020<br>ckniffin : 12/07/2020<br>carol : 07/29/2020<br>carol : 01/10/2012<br>carol : 1/10/2012<br>wwang : 8/4/2011<br>wwang : 11/23/2010<br>ckniffin : 11/18/2010<br>mcapotos : 4/24/2001<br>mcapotos : 4/16/2001<br>terry : 4/12/2001<br>mcapotos : 1/17/2001<br>mcapotos : 4/6/2000<br>mcapotos : 4/4/2000<br>terry : 3/15/2000<br>mimman : 2/8/1996<br>carol : 9/22/1992<br>supermim : 3/17/1992<br>supermim : 3/24/1990<br>supermim : 3/20/1990<br>ddp : 10/26/1989<br>root : 10/9/1989
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MONOSOMY 7 MYELODYSPLASIA AND LEUKEMIA SYNDROME 1; M7MLS1
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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MLSM7<br />
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MONOSOMY 7 OF BONE MARROW<br />
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CHROMOSOME 7q DELETION
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<strong>ORPHA:</strong> 495930;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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7q21.2
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<span class="mim-font">
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Monosomy 7 myelodysplasia and leukemia syndrome 1
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<span class="mim-font">
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252270
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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SAMD9L
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611170
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that monosomy 7 myelodysplasia and leukemia syndrome-1 (M7MLS1) is caused by heterozygous germline mutation in the SAMD9L gene (611170) on chromosome 7q21. This germline genetic defect is associated with somatic loss of chromosome 7, resulting in the deletion of several genes that may predispose to the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). One putative candidate gene is EZH2 (601573).</p><p>Heterozygous mutation in the SAMD9L gene can also cause ataxia-pancytopenia syndrome (ATXPC; 159550), which shows some overlapping features.</p>
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<strong>Description</strong>
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<p>Monosomy 7 myelodysplasia and leukemia syndrome-1 (M7MLS1) is an autosomal dominant hematologic disorder with highly variable manifestations. Most patients present in early childhood with pancytopenia and dyspoietic or dysplastic changes in the bone marrow. These abnormalities are almost always associated with monosomy 7 in the bone marrow. In severely affected individuals, the phenotype progresses to frank myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Less severely affected individuals may have transient thrombocytopenia or anemia, or have normal peripheral blood counts with transient bone marrow abnormalities or transient monosomy 7. Germline mutations in the SAMD9L gene, located on chromosome 7q, have a gain-of-function suppressive effect on the cell cycle, resulting in decreased cellular proliferation. It is hypothesized that this germline defect leads to selective pressure favoring somatic loss of the chromosome 7 harboring the mutant allele (adaptation by aneuploidy) (summary by Wong et al., 2018). </p><p>Monosomy 7 or partial deletion of the long arm of chromosome 7 (7q-) is a frequent cytogenetic finding in the bone marrow of patients with myelodysplasia and acute myelogenous leukemia. Furthermore, monosomy 7 or 7q- is the most frequent abnormality of karyotype in cases of AML that occur after cytotoxic cancer therapy or occupational exposure to mutagens. The age distribution of de novo cases shows peaks in the first and fifth decades. Monosomy 7 is found in about 5% of de novo and 40% of secondary cases of AML. These findings suggest that loss of certain genes at this region is an important event in the development of myelodysplasia (summary by Shannon et al., 1989). </p><p><strong><em>Genetic Heterogeneity of Monosomy 7 Myelodysplastic and Leukemia Syndrome</em></strong></p><p>
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See also M7MLS2 (619041), caused by germline mutation in the SAMD9 gene (610457) on chromosome 7q21.</p>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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<p>Shannon et al. (1989) studied 3 unrelated families, each with 2 patients who had MDS or AML associated with monosomy 7 in the bone marrow. The proband in the first family was a 6-year-old girl with AML and bone marrow monosomy 7. Her 5-year-old brother, who shared HLA antigens, was found during evaluation for donation of bone marrow to have mild thrombocytopenia, erythrocyte macrocytosis, and a minor subpopulation of bone marrow cells with monosomy 7. He went on to develop AML. Family 2 had 2 sisters, aged 16 and 17 years, with myelodysplasia and monosomy 7. In family 3, 2 affected brothers with a similar disorder were later found by Wong et al. (2018) to have a mutation in the SAMD9 gene, consistent with M7MLS2. </p><p>Gilchrist et al. (1990) described 2 brothers, aged 3 and 5 years, with M7MLS. Since bone marrow transplantation is the only effective treatment of M7MLS, the authors noted that familial occurrence should be kept in mind when searching for a donor. </p><p>Kwong et al. (2000) described a family with 3 sibs affected by AML in whom monosomy 7 was demonstrated. The family showed several unusual features, including the late onset of AML (34 and 37 years of age in 2 of the sibs) and the presence of an antecedent myelodysplastic phase before leukemia developed. By fluorescence in situ hybridization, the monosomy 7 clone was shown to be capable of partial maturation, which was consistent with the biologic behavior of myelodysplasia. They pointed to the earlier report of Mitelman and Heim (1992), and the reports of familial cases by Larsen and Schimke (1976), Chitambar et al. (1983), Carroll et al. (1985), and Paul et al. (1987), among others. </p><p>Minelli et al. (2001) described 2 sisters with a myelodysplastic syndrome associated with partial monosomy 7. Trisomy 8 was also present in 1 of the sisters, who later developed acute myeloid leukemia of the M0 FAB-type and died, whereas the other sister died with no evolution into AML. The authors found that the parental origin of the deleted chromosome 7 was different in the 2 sisters, thus confirming that familial monosomy 7 is not explained by a germline mutation of a possible tumor suppressor gene. Similar results were obtained in 2 other families of the 12 reported in the literature. Noteworthy was the association with a mendelian disorder in 3 of the 12 monosomy 7 families, which suggested that a mutator gene, capable of inducing both karyotype instability and a mendelian disorder, may act to induce chromosome 7 anomalies in the marrow. </p><p>Wong et al. (2018) reported 4 unrelated families with variable manifestations of M7MLS1 associated with heterozygous germline missense mutations in the SAMD9L gene (see MOLECULAR GENETICS). Two sibs in the first family presented with AML in childhood. Bone marrow examination of both sibs showed deletion of the paternal copy of chromosome 7, yielding monosomy 7. Deep sequencing showed that the SAMD9L gene was present at a low frequency (less than 5%) in the bone marrow of both children, indicating selective loss of the chromosome harboring the SAMD9L mutation. Leukemic cells in both affected sibs showed acquisition of somatic mutations in other genes, including RUNX1 (151385), SETBP1 (611060), BRAF (164757), and KRAS (164757), which likely contributed to leukemogenesis. Both patients died. The family had previously been reported as family 1 by Shannon et al. (1989). Three other affected families (families 3, 4, and 5) had a less severe phenotype. The proband in family 3 presented in early childhood with MDS and monosomy 7. She underwent successful bone marrow transplant and was well at age 27 years. Genetic studies of her sister, who had no overt hematologic abnormalities, detected a focal somatic deletion of 7q11-q36 that contained the SAMD9L gene in 7 of 27 metaphase cells. She died of an unrelated cause at age 27 years. The proband in family 4 presented at 3 years of age with pneumonia, oral candidiasis, pancytopenia, and monosomy 7 in bone marrow metaphase cells. She was treated successfully with antibiotics and her blood counts recovered. At age 7 years, cytogenetic analysis of her bone marrow was normal. Her 1.5-year-old sister was in good health with normal peripheral blood counts, although bone marrow showed monosomy 7 in 9 of 10 metaphase cells. By age 4, her bone marrow cytogenetics were normal. These patients were alive and well at 19 and 21 years of age. Eight sibs from family 5, who ranged in age from 8 to 26 years, had variable hematologic abnormalities, including anemia, cytopenia, neutropenia, and hypocellular bone marrow with dysplastic changes. None developed MDS or AML. Four patients had transient monosomy 7 in bone marrow cells that resolved over time without treatment. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of M7MLS1 in the families reported by Wong et al. (2018) was consistent with autosomal dominant inheritance with incomplete penetrance and variable expressivity. </p>
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<span class="mim-font">
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<strong>Mapping</strong>
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<p>Reasoning along the lines of the Knudson model of oncogenesis, Shannon et al. (1989) used probes that mapped to chromosome 7q22-q34 to investigate 3 families with monosomy 7. It was demonstrated that different parental chromosomes 7 were retained in the leukemic bone marrows of the sibs of these families; thus, a familial predisposition to myelodysplasia could not be located within the consistently deleted segment. In the first family studied, markers on proximal 7q showed that the leukemic chromosome 7 came from the mother in both sibs, but in 1 sib a somatic recombination had occurred, resulting in paternal derivation of the distal part of 7q in leukemic cells. In further studies of 3 pairs of sibs, Shannon et al. (1992) found no overlapping region where all 3 pairs retained DNA derived from the same paternal or maternal chromosome, suggesting that there may not be a familial disposition to the disorder resulting from germline events. However, the findings suggested that there may be multiple somatic events involving 7q in the pathogenesis of myelodysplasia. </p>
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<strong>Cytogenetics</strong>
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<p>Using microarray-based comparative genomic hybridization (CGH) analysis, Asou et al. (2009) identified a common microdeletion involving chromosome 7q21.2-q21.3 in 8 of 21 patients with juvenile myelomonocytic leukemia and normal karyotype. The microdeletion was verified by quantitative PCR analysis and involved 3 contiguous genes, SAMD9, SAMD9L, and HEPACAM2 (614133). These 3 genes were heterozygously deleted at high frequency in both adult and childhood myeloid leukemia and were commonly lost with larger deletions of chromosome 7 in 15 of 61 adult MDS/AML patients. </p><p>Nikoloski et al. (2010) identified heterozygous acquired (somatic) deletions at chromosome 7q36.1 encompassing the EZH2 (601573) and CUL1 (603134) genes in bone marrow cells derived from 13 of 102 individuals with myelodysplastic syndromes, including refractory anemia (RA). Two additional affected individuals had uniparental disomy (UPD) of this region. Genomic analysis of the remaining allele in 1 patient showed no aberrations in CUL1, but a truncating mutation in EZH2. Further sequencing of the EZH2 gene identified somatic mutations in 8 (26%) of 126 individuals, including the original 102 individuals. Three individuals had biallelic mutations. Collectively, 23% of affected individuals had deletions and/or point mutations in the EZH2 gene, and 40% of these individuals also had defects in the TET2 gene (612839). Individuals with defects at chromosome 7q showed significantly worse survival compared to those without these defects. The findings suggested that EZH2 may act as a tumor suppressor gene in some cases, and likely influences epigenetic modifications that may lead to cancer, since EZH2 functions as a histone methyltransferase. </p><p>Ernst et al. (2010) found that 9 of 12 individuals with myelodysplastic/myeloproliferative neoplasms and acquired UPD encompassing chromosome 7q36 also had a homozygous EZH2 mutation. Further sequencing of 614 individuals with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals; the mutations were found most commonly in those with myelodysplastic/myeloproliferative neoplasms (27 of 219, 12%) and in those with myelofibrosis (4 of 30, 13%). Several patients had refractory anemia, suggesting that somatic acquisition of these abnormalities may be an early event in the disease process. The mutations identified resulted in premature chain termination or direct abrogation of histone methyltransferase activity, suggesting that EZH2 can act as a tumor suppressor for myeloid malignancies. </p><p>Makishima et al. (2010) analyzed the EZH2 gene in 344 patients with myeloid malignancies, of whom 15 had UDP7q, 30 had del(7q), and 299 had no loss of heterozygosity of chromosome 7. They found 4 different EZH2 mutations in 3 (20%) of 15 patients with UDP7q and in 2 (7%) of 30 patients with del(7q); in 1 patient without LOH7q, a heterozygous frameshift mutation was identified. All were somatic mutations located in exon 18 or 19, coding for the SET domain of the EZH2 gene. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>In affected members of 4 unrelated families (families 1, 3, 4, and 5) with variable manifestations of M7MLS1, Wong et al. (2018) identified heterozygous missense mutations in the SAMD9L gene (611170.0001; 611170.0003; 611170.0005-611170.0006). The mutations, which were filtered against public databases, segregated with the disorders in the families. In vitro functional expression studies in HEK293T cells transfected with the mutations showed that they suppressed cell cycle progression and impaired cellular growth and proliferation stronger than wildtype, consistent with a gain-of-function effect. Most patients had monosomy 7, although the phenotype was variable. The sibs in family 1 had AML, ultimately resulting in early death, whereas the patients in families 3-5 had milder hematologic abnormalities and long survival. In contrast to the patients in family 1, none of the patients in families 3, 4, or 5 had somatic mutations in genes associated with the development of MDS or AML. In addition, several patients in families 3-5 had resolution of monosomy 7 without treatment, and most had additional acquired variants in the SAMD9L gene that were demonstrated or predicted to mitigate the effects of the pathogenic germline mutation. The findings emphasized the phenotypic heterogeneity in this disorder resulting from complex genetic mechanisms, including germline mutation, monosomy 7, acquired SAMD9L revertant variants, and acquired somatic changes in additional genes associated with the development of MDS or AML. </p>
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<h4>
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<span class="mim-font">
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<strong>History</strong>
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<p>The occurrence of mosaicism for trisomy 7 in normal tissues (kidney, liver, brain), as found by Mittelman (1989), is noteworthy, as is the occurrence of uniparental disomy involving chromosome 7 and leading to cystic fibrosis (see 219700).</p><p>Ruutu et al. (1977) found an association between monosomy 7 and defective chemotaxis, suggesting that a gene for normal chemotactic or chemokinetic response of neutrophils may be located on that chromosome. </p><p>De la Chapelle et al. (1982) reported that the locomotion defect of granulocytes in monosomy 7 involves random locomotion, chemotaxis, and chemokinesis.</p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<p class="mim-text-font">
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Asou, H., Matsui, H., Ozaki, Y., Nagamachi, A., Nakamura, M., Aki, D., Inaba, T.
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<strong>Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome.</strong>
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Biochem. Biophys. Res. Commun. 383: 245-251, 2009.
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[PubMed: 19358830]
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[Full Text: https://doi.org/10.1016/j.bbrc.2009.04.004]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Carroll, W. L., Morgan, R., Glader, B. E.
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<strong>Childhood bone marrow monosomy 7 syndrome: a familial disorder?</strong>
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J. Pediat. 107: 578-580, 1985.
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[PubMed: 3862804]
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[Full Text: https://doi.org/10.1016/s0022-3476(85)80027-5]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Chitambar, C. R., Robinson, W. A., Glode, L. M.
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<strong>Familial leukemia and aplastic anemia associated with monosomy 7.</strong>
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Am. J. Med. 75: 756-762, 1983.
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[PubMed: 6638045]
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[Full Text: https://doi.org/10.1016/0002-9343(83)90404-7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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de la Chapelle, A., Ruutu, P., Ruutu, T., Repo, H., Vuopio, P., Timonen, T., Kosunen, T. U.
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<strong>The locomotion defect of granulocytes in monosomy 7 involves random locomotion, chemotaxis and chemokinesis. (Abstract)</strong>
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Cytogenet. Cell Genet. 32: 264-265, 1982.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ernst, T., Chase, A. J., Score, J., Hidalgo-Curtis, C. E., Bryant, C., Jones, A. V., Waghorn, K., Zoi, K., Ross, F. M., Reiter, A., Hochhaus, A., Drexler, H. G., Duncombe, A., Cervantes, F., Oscier, D., Boultwood, J., Grand, F. H., Cross, N. C.
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<strong>Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.</strong>
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Nature Genet. 42: 722-726, 2010.
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[PubMed: 20601953]
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[Full Text: https://doi.org/10.1038/ng.621]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gilchrist, D. M., Friedman, J. M., Rogers, P. C. J., Creighton, S. P.
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<strong>Myelodysplasia and leukemia syndrome with monosomy 7: a genetic perspective.</strong>
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Am. J. Med. Genet. 35: 437-441, 1990.
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[PubMed: 2309795]
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[Full Text: https://doi.org/10.1002/ajmg.1320350323]
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</li>
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<li>
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<p class="mim-text-font">
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Kwong, Y. L., Ng, M. H., Ma, S. K.
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<strong>Familial acute myeloid leukemia with monosomy 7: late onset and involvement of a multipotential progenitor cell.</strong>
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Cancer Genet. Cytogenet. 116: 170-173, 2000.
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