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<title>
Entry
- #604321 - MICROCEPHALY 4, PRIMARY, AUTOSOMAL RECESSIVE; MCPH4
- OMIM
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<span class="h4">#604321</span>
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<strong>Table of Contents</strong>
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<li role="presentation">
<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/604321"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
<a href="/phenotypicSeries/PS251200"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#nomenclature">Nomenclature</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div style="display: table-cell;">Clinical Resources</div>
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<div><a href="https://clinicaltrials.gov/search?cond=(MICROCEPHALY 4, PRIMARY, AUTOSOMAL RECESSIVE) OR (KNL1)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=732&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>
<div><a href="https://www.diseaseinfosearch.org/x/9158" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604321[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>
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2512" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
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<div style="display: table-cell;">Animal Models</div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0070291" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/604321" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<span>
<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.">
&nbsp;
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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">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>ORPHA:</strong> 2512<br />
<strong>DO:</strong> 0070291<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
604321
</span>
</span>
</div>
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<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
MICROCEPHALY 4, PRIMARY, AUTOSOMAL RECESSIVE; MCPH4
</span>
</h3>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/102?start=-3&limit=10&highlight=102">
15q15.1
</a>
</span>
</td>
<td>
<span class="mim-font">
Microcephaly 4, primary, autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604321"> 604321 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
KNL1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609173"> 609173 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/604321" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
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</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS251200" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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&nbsp;
<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/604321" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/604321" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Microcephaly (-4 to -7 SD) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276278&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276278</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sloping forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857679&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857679</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000340" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000340</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000340" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000340</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=55cd7ed83868b07da866b39707988156" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Forehead,Sloping-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=55cd7ed83868b07da866b39707988156&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Micrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32958008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32958008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.04</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Micrognathia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Low hairline <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850639&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850639</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thick eyebrows <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853487&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853487</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000574" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000574</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000574" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000574</a>]</span><br /> -
Synophrys <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253207002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253207002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0431447&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0431447</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000664" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000664</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000664" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000664</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=d88a284723f3407bf387ee65da76603e" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Synophrys-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=d88a284723f3407bf387ee65da76603e&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Hypertelorism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22006008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22006008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/376.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">376.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020534</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eyes,Widely_Spaced-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low columella <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856119&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856119</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009765" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009765</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dcab8f2216ce1df73574c4a344dcb728" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Columella,Low_Hanging-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=dcab8f2216ce1df73574c4a344dcb728&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Mental retardation, mild to moderate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861865&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861865</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Small brain <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3151998&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3151998</a>]</span><br /> -
Speech delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/229721007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">229721007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241210&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241210</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000750</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000750</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Variable dysmorphic features may be present<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the cancer susceptibility candidate 5 gene (CASC5, <a href="/entry/609173#0001">609173.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Microcephaly, primary
- <a href="/phenotypicSeries/PS251200">PS251200</a>
- 30 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/482?start=-3&limit=10&highlight=482"> 1p34.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616486"> Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain abnormalities </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616486"> 616486 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614397"> MFSD2A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614397"> 614397 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/592?start=-3&limit=10&highlight=592"> 1p33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612703"> Microcephaly 7, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612703"> 612703 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/181590"> STIL </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/181590"> 181590 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/835?start=-3&limit=10&highlight=835"> 1p21.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616402"> Microcephaly 14, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616402"> 616402 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609321"> SASS6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609321"> 609321 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1535?start=-3&limit=10&highlight=1535"> 1q31.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608716"> Microcephaly 5, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608716"> 608716 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605481"> ASPM </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605481"> 605481 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1552?start=-3&limit=10&highlight=1552"> 1q32.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617914"> Microcephaly 20, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617914"> 617914 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611279"> KIF14 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611279"> 611279 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/478?start=-3&limit=10&highlight=478"> 2q11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617985"> ?Microcephaly 23, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617985"> 617985 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602332"> NCAPH </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602332"> 602332 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/558?start=-3&limit=10&highlight=558"> 2q13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620183"> Microcephaly 30, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620183"> 620183 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602452"> BUB1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602452"> 602452 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/155?start=-3&limit=10&highlight=155"> 3p22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620047"> ?Microcephaly 29, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620047"> 620047 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608074"> PDCD6IP </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608074"> 608074 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/727?start=-3&limit=10&highlight=727"> 3q23 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617800"> ?Microcephaly 19, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617800"> 617800 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606990"> COPB2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606990"> 606990 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/234?start=-3&limit=10&highlight=234"> 4q12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614673"> Microcephaly 8, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614673"> 614673 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611423"> CEP135 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611423"> 611423 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/379?start=-3&limit=10&highlight=379"> 4q21.23 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617520"> ?Microcephaly 18, primary, autosomal dominant </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617520"> 617520 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617485"> WDFY3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617485"> 617485 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/455?start=-3&limit=10&highlight=455"> 4q24 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616051"> ?Microcephaly 13, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616051"> 616051 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/117143"> CENPE </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/117143"> 117143 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/408?start=-3&limit=10&highlight=408"> 5q23.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619179"> Microcephaly 26, primary, autosomal dominant </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619179"> 619179 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/150340"> LMNB1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/150340"> 150340 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/412?start=-3&limit=10&highlight=412"> 7q21.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616080"> ?Microcephaly 12, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616080"> 616080 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603368"> CDK6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603368"> 603368 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/489?start=-3&limit=10&highlight=489"> 7q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618351"> ?Microcephaly 25, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618351"> 618351 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618350"> MAP11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618350"> 618350 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/16?start=-3&limit=10&highlight=16"> 8p23.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/251200"> Microcephaly 1, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/251200"> 251200 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607117"> MCPH1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607117"> 607117 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/456?start=-3&limit=10&highlight=456"> 9q33.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604804"> Microcephaly 3, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604804"> 604804 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608201"> CDK5RAP2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608201"> 608201 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/1102?start=-3&limit=10&highlight=1102"> 11q25 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617984"> Microcephaly 22, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617984"> 617984 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609276"> NCAPD3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609276"> 609276 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/55?start=-3&limit=10&highlight=55"> 12p13.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617983"> Microcephaly 21, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617983"> 617983 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615638"> NCAPD2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615638"> 615638 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/118?start=-3&limit=10&highlight=118"> 12p13.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615414"> ?Microcephaly 11, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615414"> 615414 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602978"> PHC1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602978"> 602978 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/734?start=-3&limit=10&highlight=734"> 12q23.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618179"> ?Microcephaly 24, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618179"> 618179 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609264"> NUP37 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609264"> 609264 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/861?start=-3&limit=10&highlight=861"> 12q24.23 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617090"> Microcephaly 17, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617090"> 617090 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605629"> CIT </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605629"> 605629 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/968?start=-3&limit=10&highlight=968"> 12q24.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616681"> Microcephaly 16, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616681"> 616681 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616062"> ANKLE2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616062"> 616062 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/13/41?start=-3&limit=10&highlight=41"> 13q12.12-q12.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608393"> Microcephaly 6, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608393"> 608393 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609279"> CENPJ </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609279"> 609279 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/102?start=-3&limit=10&highlight=102"> 15q15.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604321"> Microcephaly 4, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604321"> 604321 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609173"> KNL1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609173"> 609173 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/193?start=-3&limit=10&highlight=193"> 15q21.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614852"> Microcephaly 9, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614852"> 614852 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613529"> CEP152 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613529"> 613529 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/89?start=-3&limit=10&highlight=89"> 19p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619180"> Microcephaly 27, primary, autosomal dominant </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619180"> 619180 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/150341"> LMNB2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/150341"> 150341 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/614?start=-3&limit=10&highlight=614"> 19q13.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604317"> Microcephaly 2, primary, autosomal recessive, with or without cortical malformations </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604317"> 604317 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613583"> WDR62 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613583"> 613583 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/20/351?start=-3&limit=10&highlight=351"> 20q13.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615095"> Microcephaly 10, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615095"> 615095 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610827"> ZNF335 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610827"> 610827 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/22/347?start=-3&limit=10&highlight=347"> 22q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619453"> ?Microcephaly 28, primary, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619453"> 619453 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619449"> RRP7A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619449"> 619449 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
</span>
</span>
</h4>
<div id="mimTextFold" class="collapse in ">
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because of evidence that autosomal recessive primary microcephaly-4 (MCPH4) is caused by homozygous or compound heterozygous mutation in the CASC5 gene (KNL1; <a href="/entry/609173">609173</a>) on chromosome 15q15.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="description" class="mim-anchor"></a>
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>Primary microcephaly (MCPH) is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations below the age- and sex-matched population mean and mental retardation, with no other associated malformations and with no apparent etiology. Most cases of primary microcephaly show an autosomal recessive mode of inheritance (summary by <a href="#5" class="mim-tip-reference" title="Woods, C. G., Bond, J., Enard, W. &lt;strong&gt;Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings.&lt;/strong&gt; Am. J. Hum. Genet. 76: 717-728, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15806441/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15806441&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15806441[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/429930&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15806441">Woods et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15806441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (<a href="/entry/251200">251200</a>).</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#3" class="mim-tip-reference" title="Jamieson, C. R., Govaerts, C., Abramowicz, M. J. &lt;strong&gt;Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 65: 1465-1469, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10521316/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10521316&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10521316[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302640&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10521316">Jamieson et al. (1999)</a> reported 4 sibs, born of consanguineous Moroccan parents, with primary microcephaly (head circumference -5 to -6 SD). The patients also had poor overall growth and mental retardation. Brain CT scan of the proband showed enlarged ventricles, but no other abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10521316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., Abramowicz, M. &lt;strong&gt;Kinetochore KMN network gene CASC5 mutated in primary microcephaly.&lt;/strong&gt; Hum. Molec. Genet. 21: 5306-5317, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22983954/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22983954&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds386&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22983954">Genin et al. (2012)</a> provided follow-up of the family reported by <a href="#3" class="mim-tip-reference" title="Jamieson, C. R., Govaerts, C., Abramowicz, M. J. &lt;strong&gt;Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 65: 1465-1469, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10521316/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10521316&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10521316[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302640&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10521316">Jamieson et al. (1999)</a> and reported 2 additional similarly affected families. All were consanguineous and of Moroccan origin from small villages about 50 km apart. All patients had head circumferences of -4 to -7 SD and mild to moderate mental retardation. Stature and motor development was normal; none had seizures or neurologic deficits. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10521316+22983954" 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="Saadi, A., Verny, F., Siquier-Pernet, K., Bole-Feysot, C., Nitschke, P., Munnich, A., Abada-Dendib, M., Chaouch, M., Abramowicz, M., Colleaux, L. &lt;strong&gt;Refining the phenotype associated with CASC5 mutation.&lt;/strong&gt; Neurogenetics 17: 71-78, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/26626498/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;26626498&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-015-0468-7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="26626498">Saadi et al. (2016)</a> described 4 sibs in a consanguineous Algerian family with primary microcephaly. Low head circumference at birth was noted by the parents. Psychomotor development was delayed, with all affected individuals starting to walk at the age of 18 months and showing reduced verbal fluency, only producing a few words. At the age of 23 to 29 years, the patients had marked speech delay and moderate to severe cognitive deficit. They were unable to write, read, count or confirm their ages. Two had difficulty eating, walking, and dressing independently. All had a sloping forehead, thick eyebrows, synophrys, and low columella. Head circumferences ranged from -3 to -4 SD below the mean for age and gender, and all had short stature. Cerebral MRI in 2 sibs showed a small brain, shortened frontal lobe, dilated occipital horns, and cerebellar vermis hypoplasia in one, and only a small brain in the other. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26626498" 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="Zarate, Y. A., Kaylor, J. A., Bosanko, K., Lau, S., Vargas, J., Gao, H. &lt;strong&gt;First clinical report of an infant with microcephaly and CASC5 mutations. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 170A: 2215-2218, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/27149178/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;27149178&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.37726&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="27149178">Zarate et al. (2016)</a> reported an African American male infant with primary microcephaly. At birth, the boy weighed 3.08 kg, was 49.5 cm long, and had an OFC of 31.1 cm. While his length and weight measurements fluctuated between low-for-age and normal during the first year of life, his OFC was consistently below -3 SD for age. An MRI at 7 months of age showed simplified gyral pattern and a very mild delay of myelination. At 17 months of age, he had severe microcephaly (-4.88 SD) but had achieved normal milestones. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27149178" 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 primary microcephaly in the family reported by <a href="#3" class="mim-tip-reference" title="Jamieson, C. R., Govaerts, C., Abramowicz, M. J. &lt;strong&gt;Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 65: 1465-1469, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10521316/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10521316&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10521316[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302640&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10521316">Jamieson et al. (1999)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10521316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#3" class="mim-tip-reference" title="Jamieson, C. R., Govaerts, C., Abramowicz, M. J. &lt;strong&gt;Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 65: 1465-1469, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10521316/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10521316&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10521316[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302640&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10521316">Jamieson et al. (1999)</a> reported homozygosity mapping of a novel locus, which they termed MCPH4, at 15q15-q21 in a consanguineous Moroccan family with primary microcephaly. By homozygosity mapping of the family reported by <a href="#3" class="mim-tip-reference" title="Jamieson, C. R., Govaerts, C., Abramowicz, M. J. &lt;strong&gt;Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 65: 1465-1469, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10521316/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10521316&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10521316[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302640&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10521316">Jamieson et al. (1999)</a>, <a href="#1" class="mim-tip-reference" title="Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., Abramowicz, M. &lt;strong&gt;Kinetochore KMN network gene CASC5 mutated in primary microcephaly.&lt;/strong&gt; Hum. Molec. Genet. 21: 5306-5317, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22983954/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22983954&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds386&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22983954">Genin et al. (2012)</a> narrowed the candidate region to a 3.7-Mb interval at 15q14-q15, which excluded the CEP152 gene (<a href="/entry/613529">613529</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10521316+22983954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By homozygosity mapping followed by candidate gene sequencing in 3 Moroccan families with primary microcephaly, including the family originally reported by <a href="#3" class="mim-tip-reference" title="Jamieson, C. R., Govaerts, C., Abramowicz, M. J. &lt;strong&gt;Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 65: 1465-1469, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10521316/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10521316&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10521316[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302640&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10521316">Jamieson et al. (1999)</a>, <a href="#1" class="mim-tip-reference" title="Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., Abramowicz, M. &lt;strong&gt;Kinetochore KMN network gene CASC5 mutated in primary microcephaly.&lt;/strong&gt; Hum. Molec. Genet. 21: 5306-5317, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22983954/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22983954&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds386&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22983954">Genin et al. (2012)</a> identified a homozygous missense mutation (M2041I; <a href="/entry/609173#0001">609173.0001</a>) in the CASC5 gene (<a href="/entry/609173#0001">609173.0001</a>). None of the patients had a mutation in the CEP152 gene. Haplotype analysis indicated a founder effect. The mutation was predicted to inactivate an exonic splicing enhancer, and was demonstrated to result in abnormal splicing and production of a transcript lacking exon 18 and causing premature termination. However, normal CASC5 protein levels were also found in patient lymphoblastoid cells. Patient lymphoblasts showed no abnormalities in mitosis, no changes in growth rate, and no micronuclei. Immunofluorescence studies showed no defects of CASC5 expression in patient fibroblasts, and mitotic spindles were normal. None of the patients developed leukemia, consistent with normal CASC5 function in nonneurologic cells. Although this mutant CASC5 appeared to function normally in patient lymphoblasts and fibroblasts, <a href="#1" class="mim-tip-reference" title="Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., Abramowicz, M. &lt;strong&gt;Kinetochore KMN network gene CASC5 mutated in primary microcephaly.&lt;/strong&gt; Hum. Molec. Genet. 21: 5306-5317, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22983954/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22983954&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds386&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22983954">Genin et al. (2012)</a> speculated that it may express the defect only in neural cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10521316+22983954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a consanguineous Algerian family with primary microcephaly, <a href="#4" class="mim-tip-reference" title="Saadi, A., Verny, F., Siquier-Pernet, K., Bole-Feysot, C., Nitschke, P., Munnich, A., Abada-Dendib, M., Chaouch, M., Abramowicz, M., Colleaux, L. &lt;strong&gt;Refining the phenotype associated with CASC5 mutation.&lt;/strong&gt; Neurogenetics 17: 71-78, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/26626498/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;26626498&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-015-0468-7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="26626498">Saadi et al. (2016)</a> identified homozygosity for the same M2041I mutation in the CASC5 gene that had been identified by <a href="#1" class="mim-tip-reference" title="Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., Abramowicz, M. &lt;strong&gt;Kinetochore KMN network gene CASC5 mutated in primary microcephaly.&lt;/strong&gt; Hum. Molec. Genet. 21: 5306-5317, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22983954/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22983954&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds386&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22983954">Genin et al. (2012)</a> in Moroccan families. Haplotype analysis supported the existence of a common ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22983954+26626498" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an African American male infant with primary microcephaly, <a href="#6" class="mim-tip-reference" title="Zarate, Y. A., Kaylor, J. A., Bosanko, K., Lau, S., Vargas, J., Gao, H. &lt;strong&gt;First clinical report of an infant with microcephaly and CASC5 mutations. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 170A: 2215-2218, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/27149178/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;27149178&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.37726&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="27149178">Zarate et al. (2016)</a> identified compound heterozygosity for a de novo frameshift (<a href="/entry/609173#0002">609173.0002</a>) mutation and a maternally inherited missense (D2187G; <a href="/entry/609173#0003">609173.0003</a>) mutation in the CASC5 gene. (<a href="#6" class="mim-tip-reference" title="Zarate, Y. A., Kaylor, J. A., Bosanko, K., Lau, S., Vargas, J., Gao, H. &lt;strong&gt;First clinical report of an infant with microcephaly and CASC5 mutations. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 170A: 2215-2218, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/27149178/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;27149178&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.37726&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="27149178">Zarate et al. (2016)</a> incorrectly stated the protein change as D2178G.) The frameshift mutation was not found in the dbSNP, Exome Variant Server, or ExAC databases; the missense mutation was present in the ExAC database at a low frequency in the general population, but primarily in patients of African ancestry, with a heterozygous minor allele frequency of 0.0034 in that population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27149178" 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>Exclusion Studies</em></strong></p><p>
<a href="#1" class="mim-tip-reference" title="Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., Abramowicz, M. &lt;strong&gt;Kinetochore KMN network gene CASC5 mutated in primary microcephaly.&lt;/strong&gt; Hum. Molec. Genet. 21: 5306-5317, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22983954/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22983954&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds386&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22983954">Genin et al. (2012)</a> directly sequenced the CASC5 gene in a cohort of patients with primary microcephaly, including 3 probands from consanguineous families with homozygosity at the MCPH4 locus, and did not find any additional mutations, suggesting that CASC5 mutations are a rare cause of microcephaly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22983954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="nomenclature" class="mim-anchor"></a>
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<strong>Nomenclature</strong>
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<p>Although MCPH4 was originally thought to be due to mutation in the CEP152 gene on chromosome 15q21 based on the report of <a href="#2" class="mim-tip-reference" title="Guernsey, D. L., Jiang, H., Hussin, J., Arnold, M., Bouyakdan, K., Perry, S., Babineau-Sturk, T., Beis, J., Dumas, N., Evans, S. C., Ferguson, M., Matsuoka, M., and 12 others. &lt;strong&gt;Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4.&lt;/strong&gt; Am. J. Hum. Genet. 87: 40-51, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20598275/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20598275&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20598275[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2010.06.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20598275">Guernsey et al. (2010)</a>, <a href="#1" class="mim-tip-reference" title="Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., Abramowicz, M. &lt;strong&gt;Kinetochore KMN network gene CASC5 mutated in primary microcephaly.&lt;/strong&gt; Hum. Molec. Genet. 21: 5306-5317, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22983954/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22983954&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds386&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22983954">Genin et al. (2012)</a> later identified a mutation in the CASC5 gene on 15q14 in the original family with MCPH4 (<a href="#3" class="mim-tip-reference" title="Jamieson, C. R., Govaerts, C., Abramowicz, M. J. &lt;strong&gt;Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 65: 1465-1469, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10521316/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10521316&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10521316[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302640&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10521316">Jamieson et al., 1999</a>). Microcephaly caused by mutation in the CEP152 gene is now designated MCPH9 (<a href="/entry/614852">614852</a>), and microcephaly caused by mutation in the CASC5 gene is now designated MCPH4. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10521316+22983954+20598275" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="references"class="mim-anchor"></a>
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<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<a id="1" class="mim-anchor"></a>
<a id="Genin2012" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., Abramowicz, M.
<strong>Kinetochore KMN network gene CASC5 mutated in primary microcephaly.</strong>
Hum. Molec. Genet. 21: 5306-5317, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22983954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22983954</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22983954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/dds386" target="_blank">Full Text</a>]
</p>
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<a id="2" class="mim-anchor"></a>
<a id="Guernsey2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Guernsey, D. L., Jiang, H., Hussin, J., Arnold, M., Bouyakdan, K., Perry, S., Babineau-Sturk, T., Beis, J., Dumas, N., Evans, S. C., Ferguson, M., Matsuoka, M., and 12 others.
<strong>Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4.</strong>
Am. J. Hum. Genet. 87: 40-51, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20598275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20598275</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20598275[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20598275" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ajhg.2010.06.003" target="_blank">Full Text</a>]
</p>
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<a id="3" class="mim-anchor"></a>
<a id="Jamieson1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jamieson, C. R., Govaerts, C., Abramowicz, M. J.
<strong>Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. (Letter)</strong>
Am. J. Hum. Genet. 65: 1465-1469, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521316</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10521316[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10521316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/302640" target="_blank">Full Text</a>]
</p>
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<a id="4" class="mim-anchor"></a>
<a id="Saadi2016" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Saadi, A., Verny, F., Siquier-Pernet, K., Bole-Feysot, C., Nitschke, P., Munnich, A., Abada-Dendib, M., Chaouch, M., Abramowicz, M., Colleaux, L.
<strong>Refining the phenotype associated with CASC5 mutation.</strong>
Neurogenetics 17: 71-78, 2016.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26626498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26626498</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26626498" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s10048-015-0468-7" target="_blank">Full Text</a>]
</p>
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<a id="Woods2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Woods, C. G., Bond, J., Enard, W.
<strong>Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings.</strong>
Am. J. Hum. Genet. 76: 717-728, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15806441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15806441</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15806441[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15806441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/429930" target="_blank">Full Text</a>]
</p>
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<a id="Zarate2016" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zarate, Y. A., Kaylor, J. A., Bosanko, K., Lau, S., Vargas, J., Gao, H.
<strong>First clinical report of an infant with microcephaly and CASC5 mutations. (Letter)</strong>
Am. J. Med. Genet. 170A: 2215-2218, 2016.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27149178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27149178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27149178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.37726" target="_blank">Full Text</a>]
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<span class="mim-text-font">
Joanna S. Amberger - updated : 02/19/2018
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<span class="mim-text-font">
Cassandra L. Kniffin - updated : 10/18/2012<br>Cassandra L. Kniffin - updated : 9/16/2010
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Creation Date:
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Victor A. McKusick : 11/30/1999
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 12/05/2024
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alopez : 06/03/2024<br>carol : 02/20/2018<br>carol : 06/01/2017<br>carol : 09/26/2013<br>carol : 1/25/2013<br>carol : 10/22/2012<br>ckniffin : 10/18/2012<br>wwang : 6/2/2011<br>wwang : 9/17/2010<br>wwang : 9/17/2010<br>ckniffin : 9/16/2010<br>mgross : 3/18/2004<br>mgross : 8/6/2002<br>mgross : 4/7/2000<br>mgross : 11/30/1999
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<strong>#</strong> 604321
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MICROCEPHALY 4, PRIMARY, AUTOSOMAL RECESSIVE; MCPH4
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<strong>ORPHA:</strong> 2512; &nbsp;
<strong>DO:</strong> 0070291; &nbsp;
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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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15q15.1
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Microcephaly 4, primary, autosomal recessive
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604321
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Autosomal recessive
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3
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KNL1
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609173
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that autosomal recessive primary microcephaly-4 (MCPH4) is caused by homozygous or compound heterozygous mutation in the CASC5 gene (KNL1; 609173) on chromosome 15q15.</p>
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<strong>Description</strong>
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<p>Primary microcephaly (MCPH) is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations below the age- and sex-matched population mean and mental retardation, with no other associated malformations and with no apparent etiology. Most cases of primary microcephaly show an autosomal recessive mode of inheritance (summary by Woods et al., 2005). </p><p>For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).</p>
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<strong>Clinical Features</strong>
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<p>Jamieson et al. (1999) reported 4 sibs, born of consanguineous Moroccan parents, with primary microcephaly (head circumference -5 to -6 SD). The patients also had poor overall growth and mental retardation. Brain CT scan of the proband showed enlarged ventricles, but no other abnormalities. </p><p>Genin et al. (2012) provided follow-up of the family reported by Jamieson et al. (1999) and reported 2 additional similarly affected families. All were consanguineous and of Moroccan origin from small villages about 50 km apart. All patients had head circumferences of -4 to -7 SD and mild to moderate mental retardation. Stature and motor development was normal; none had seizures or neurologic deficits. </p><p>Saadi et al. (2016) described 4 sibs in a consanguineous Algerian family with primary microcephaly. Low head circumference at birth was noted by the parents. Psychomotor development was delayed, with all affected individuals starting to walk at the age of 18 months and showing reduced verbal fluency, only producing a few words. At the age of 23 to 29 years, the patients had marked speech delay and moderate to severe cognitive deficit. They were unable to write, read, count or confirm their ages. Two had difficulty eating, walking, and dressing independently. All had a sloping forehead, thick eyebrows, synophrys, and low columella. Head circumferences ranged from -3 to -4 SD below the mean for age and gender, and all had short stature. Cerebral MRI in 2 sibs showed a small brain, shortened frontal lobe, dilated occipital horns, and cerebellar vermis hypoplasia in one, and only a small brain in the other. </p><p>Zarate et al. (2016) reported an African American male infant with primary microcephaly. At birth, the boy weighed 3.08 kg, was 49.5 cm long, and had an OFC of 31.1 cm. While his length and weight measurements fluctuated between low-for-age and normal during the first year of life, his OFC was consistently below -3 SD for age. An MRI at 7 months of age showed simplified gyral pattern and a very mild delay of myelination. At 17 months of age, he had severe microcephaly (-4.88 SD) but had achieved normal milestones. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of primary microcephaly in the family reported by Jamieson et al. (1999) was consistent with autosomal recessive inheritance. </p>
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<strong>Mapping</strong>
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<p>Jamieson et al. (1999) reported homozygosity mapping of a novel locus, which they termed MCPH4, at 15q15-q21 in a consanguineous Moroccan family with primary microcephaly. By homozygosity mapping of the family reported by Jamieson et al. (1999), Genin et al. (2012) narrowed the candidate region to a 3.7-Mb interval at 15q14-q15, which excluded the CEP152 gene (613529). </p>
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<strong>Molecular Genetics</strong>
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<p>By homozygosity mapping followed by candidate gene sequencing in 3 Moroccan families with primary microcephaly, including the family originally reported by Jamieson et al. (1999), Genin et al. (2012) identified a homozygous missense mutation (M2041I; 609173.0001) in the CASC5 gene (609173.0001). None of the patients had a mutation in the CEP152 gene. Haplotype analysis indicated a founder effect. The mutation was predicted to inactivate an exonic splicing enhancer, and was demonstrated to result in abnormal splicing and production of a transcript lacking exon 18 and causing premature termination. However, normal CASC5 protein levels were also found in patient lymphoblastoid cells. Patient lymphoblasts showed no abnormalities in mitosis, no changes in growth rate, and no micronuclei. Immunofluorescence studies showed no defects of CASC5 expression in patient fibroblasts, and mitotic spindles were normal. None of the patients developed leukemia, consistent with normal CASC5 function in nonneurologic cells. Although this mutant CASC5 appeared to function normally in patient lymphoblasts and fibroblasts, Genin et al. (2012) speculated that it may express the defect only in neural cells. </p><p>In affected members of a consanguineous Algerian family with primary microcephaly, Saadi et al. (2016) identified homozygosity for the same M2041I mutation in the CASC5 gene that had been identified by Genin et al. (2012) in Moroccan families. Haplotype analysis supported the existence of a common ancestor. </p><p>In an African American male infant with primary microcephaly, Zarate et al. (2016) identified compound heterozygosity for a de novo frameshift (609173.0002) mutation and a maternally inherited missense (D2187G; 609173.0003) mutation in the CASC5 gene. (Zarate et al. (2016) incorrectly stated the protein change as D2178G.) The frameshift mutation was not found in the dbSNP, Exome Variant Server, or ExAC databases; the missense mutation was present in the ExAC database at a low frequency in the general population, but primarily in patients of African ancestry, with a heterozygous minor allele frequency of 0.0034 in that population. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
Genin et al. (2012) directly sequenced the CASC5 gene in a cohort of patients with primary microcephaly, including 3 probands from consanguineous families with homozygosity at the MCPH4 locus, and did not find any additional mutations, suggesting that CASC5 mutations are a rare cause of microcephaly. </p>
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<strong>Nomenclature</strong>
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<p>Although MCPH4 was originally thought to be due to mutation in the CEP152 gene on chromosome 15q21 based on the report of Guernsey et al. (2010), Genin et al. (2012) later identified a mutation in the CASC5 gene on 15q14 in the original family with MCPH4 (Jamieson et al., 1999). Microcephaly caused by mutation in the CEP152 gene is now designated MCPH9 (614852), and microcephaly caused by mutation in the CASC5 gene is now designated MCPH4. </p>
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<strong>REFERENCES</strong>
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Genin, A., Desir, J., Lambert, N., Biervliet, M., Van Der Aa, N., Pierquin, G., Killian, A., Tosi, M., Urbina, M., Lefort, A., Libert, F., Pirson, I., Abramowicz, M.
<strong>Kinetochore KMN network gene CASC5 mutated in primary microcephaly.</strong>
Hum. Molec. Genet. 21: 5306-5317, 2012.
[PubMed: 22983954]
[Full Text: https://doi.org/10.1093/hmg/dds386]
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Guernsey, D. L., Jiang, H., Hussin, J., Arnold, M., Bouyakdan, K., Perry, S., Babineau-Sturk, T., Beis, J., Dumas, N., Evans, S. C., Ferguson, M., Matsuoka, M., and 12 others.
<strong>Mutations in centrosomal protein CEP152 in primary microcephaly families linked to MCPH4.</strong>
Am. J. Hum. Genet. 87: 40-51, 2010.
[PubMed: 20598275]
[Full Text: https://doi.org/10.1016/j.ajhg.2010.06.003]
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Jamieson, C. R., Govaerts, C., Abramowicz, M. J.
<strong>Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15. (Letter)</strong>
Am. J. Hum. Genet. 65: 1465-1469, 1999.
[PubMed: 10521316]
[Full Text: https://doi.org/10.1086/302640]
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Saadi, A., Verny, F., Siquier-Pernet, K., Bole-Feysot, C., Nitschke, P., Munnich, A., Abada-Dendib, M., Chaouch, M., Abramowicz, M., Colleaux, L.
<strong>Refining the phenotype associated with CASC5 mutation.</strong>
Neurogenetics 17: 71-78, 2016.
[PubMed: 26626498]
[Full Text: https://doi.org/10.1007/s10048-015-0468-7]
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Woods, C. G., Bond, J., Enard, W.
<strong>Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings.</strong>
Am. J. Hum. Genet. 76: 717-728, 2005.
[PubMed: 15806441]
[Full Text: https://doi.org/10.1086/429930]
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Zarate, Y. A., Kaylor, J. A., Bosanko, K., Lau, S., Vargas, J., Gao, H.
<strong>First clinical report of an infant with microcephaly and CASC5 mutations. (Letter)</strong>
Am. J. Med. Genet. 170A: 2215-2218, 2016.
[PubMed: 27149178]
[Full Text: https://doi.org/10.1002/ajmg.a.37726]
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Contributors:
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Joanna S. Amberger - updated : 02/19/2018<br>Cassandra L. Kniffin - updated : 10/18/2012<br>Cassandra L. Kniffin - updated : 9/16/2010
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Creation Date:
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Victor A. McKusick : 11/30/1999
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