4933 lines
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Entry
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- *300121 - DOUBLECORTIN; DCX
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*300121</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/300121">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000077279;t=ENST00000636035" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=1641" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=300121" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000077279;t=ENST00000636035" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000555,NM_001195553,NM_001369370,NM_001369371,NM_001369372,NM_001369373,NM_001369374,NM_001410715,NM_178151,NM_178152,NM_178153" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001195553" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=300121" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=02127&isoform_id=02127_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/DCX" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/2739176,2764748,2792348,2792350,3114810,20381233,30181240,30181242,30181244,30181246,119623047,119623048,119623049,119623050,119623051,119623052,119623053,119623054,158261933,194386402,194389450,307078115,1018583372,1609036688,1609037422,1609042343,1609045048,1609045673,2286439330" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/O43602" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=1641" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000077279;t=ENST00000636035" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=DCX" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=DCX" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+1641" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/DCX" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:1641" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/1641" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chrX&hgg_gene=ENST00000636035.2&hgg_start=111293779&hgg_end=111412192&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:2714" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2714" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/dcx" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300121[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300121[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/DCX/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000077279" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.gwascentral.org/search?q=DCX" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=DCX" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=DCX&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA27184" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:2714" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0261387.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1277171" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/DCX#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:1277171" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/1641/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002891/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1641" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=DCX&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
|
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300121
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
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<span class="mim-font">
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DOUBLECORTIN; DCX
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
|
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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DBCN
|
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</span>
|
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DCX" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DCX</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/X/575?start=-3&limit=10&highlight=575">Xq23</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:111293779-111412192&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">X:111,293,779-111,412,192</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
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Location
|
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</th>
|
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<th>
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Phenotype
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</th>
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<th>
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|
Phenotype <br /> MIM number
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</th>
|
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<th>
|
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
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|
|
<tr>
|
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<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/575?start=-3&limit=10&highlight=575">
|
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Xq23
|
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</a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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Lissencephaly, X-linked
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/300067"> 300067 </a>
|
|
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="X-linked">XL</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Subcortical laminal heterotopia, X-linked
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300067"> 300067 </a>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked">XL</abbr>
|
|
|
|
</span>
|
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</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>
|
|
</tr>
|
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</tbody>
|
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</table>
|
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</div>
|
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</div>
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<div>
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<div class="btn-group">
|
|
<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/300121" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/300121" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
|
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<br />
|
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</div>
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<p>By positional cloning of a brain-specific cDNA spanning an Xq22 breakpoint in a female with lissencephaly (LISX1; <a href="/entry/300067">300067</a>), <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> identified a gene, termed 'doublecortin' (DCX), that encodes a 360-residue protein with a predicted molecular mass of 40 kD and a putative Abl (<a href="/entry/189980">189980</a>) phosphorylation site. Northern blot analysis identified a 10-kb mRNA transcript with exclusive expression in fetal brain tissue and multiple splice variants. Independently, <a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">des Portes et al. (1998)</a> used a YAC clone spanning the Xq22.3-q23 candidate LISX1 region identified by linkage studies (<a href="#8" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Smadja, D., Motte, J., Boespflug-Tanguy, O., Moutard, M. L., Desguerre, I., Billuart, P., Carrie, A., Bienvenu, T., Vinet, M. C., Bachner, L., Beldjord, C., Dulac, O., Kahn, A., Ponsot, G., Chelly, J. <strong>Dominant X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH/LIS): evidence for the occurrence of mutation in males and mapping of a potential locus in Xq22.</strong> J. Med. Genet. 34: 177-183, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9132485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9132485</a>] [<a href="https://doi.org/10.1136/jmg.34.3.177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9132485">des Portes et al., 1997</a>; <a href="#24" class="mim-tip-reference" title="Ross, M. E., Allen, K. M., Srivastava, A. K., Featherstone, T., Gleeson, J. G., Hirsch, B., Harding, B. N., Andermann, E., Abdullah, R., Berg, M., Czapansky-Bielman, D., Flanders, D. J., and 11 others. <strong>Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): a gene causing neuronal migration defects in human brain.</strong> Hum. Molec. Genet. 6: 555-562, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097958</a>] [<a href="https://doi.org/10.1093/hmg/6.4.555" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9097958">Ross et al., 1997</a>) to identify a cDNA corresponding to the DCX gene from a human fetal brain cDNA library. The authors also found a 9.5-kb mRNA transcript that was expressed only in fetal brain. Both <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> and <a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">des Portes et al. (1998)</a> predicted that doublecortin is required for neuronal migration and may be involved in signal transduction. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9097958+9489699+9489700+9132485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">Des Portes et al. (1998)</a> and <a href="#27" class="mim-tip-reference" title="Sossey-Alaoui, K., Hartung, A. J., Guerrini, R., Manchester, D. K., Posar, A., Puche-Mira, A., Andermann, E., Dobyns, W. B., Srivastava, A. K. <strong>Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca(2+)-dependent signaling protein which is mutated in human X-linked neuronal migration defects.</strong> Hum. Molec. Genet. 7: 1327-1332, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9668176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9668176</a>] [<a href="https://doi.org/10.1093/hmg/7.8.1327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9668176">Sossey-Alaoui et al. (1998)</a> cloned the mouse Dcx gene. It encodes isoforms of a highly hydrophilic 40-kD protein, homologous to its human counterpart and containing several potential phosphorylation sites. Both human and mouse DCX proteins are homologous to a CNS protein containing a Ca(2+)/calmodulin kinase domain (DCAMKL1; <a href="/entry/604742">604742</a>), suggesting that the DCX protein may belong to a novel class of intracellular proteins involved in neuronal migration through Ca(2+)-dependent signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9668176+9489699" 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="#17" class="mim-tip-reference" title="Leger, P.-L., Souville, I., Boddaert, N., Elie, C., Pinard, J. M., Plouin, P., Moutard, M. L., des Portes, V., Van Esch, H., Joriot, S., Renard, J. L., Chelly, J., Francis, F., Beldjord, C., Bahi-Buisson, N. <strong>The location of DCX mutations predicts malformation severity in X-linked lissencephaly.</strong> Neurogenetics 9: 277-285, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18685874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18685874</a>] [<a href="https://doi.org/10.1007/s10048-008-0141-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18685874">Leger et al. (2008)</a> noted that the doublecortin domain consists of 2 evolutionarily conserved repeats, namely N-DC from amino acids 42 to 150 and C-DC from amino acids 171 to 275, that play a role in microtubule binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18685874" 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="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> and <a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">des Portes et al. (1998)</a> determined that the DCX gene spans over 100 kb of DNA and contains 9 exons with 6 coding exons. The structure of the gene is unusual because only 16% of the sequence is coding, and the 3-prime untranslated region, which is contained in 1 exon, is 7.9 kb long. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9489699+9489700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using in situ hybridization, <a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">des Portes et al. (1998)</a> observed DCX expression in human cerebral cortex at 21 weeks' gestational age. There was strong labeling in the ventricular zone and cortical plate and moderate labeling of the intermediate zone. In the intermediate zone, labeled cells were organized as oriented chains, suggestive of migrating neurons. Studies in mouse embryonic brain showed significant Dcx expression primarily in neuronal cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489699" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Caspi, M., Atlas, R., Kantor, A., Sapir, T., Reiner, O. <strong>Interaction between LIS1 and doublecortin, two lissencephaly gene products.</strong> Hum. Molec. Genet. 9: 2205-2213, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11001923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11001923</a>] [<a href="https://doi.org/10.1093/oxfordjournals.hmg.a018911" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11001923">Caspi et al. (2000)</a> demonstrated an interaction of the DCX gene with the LIS1 gene (PAFAH1B1; <a href="/entry/601545">601545</a>) by coimmunoprecipitation, both in transiently transfected cells and in embryonic brain extracts. Immunofluorescence studies revealed that the 2 protein products colocalized in transfected cells and in primary neuronal cells. LIS1 and DCX enhanced tubulin polymerization in an additive fashion, as measured by a light-scattering assay in vitro. The authors hypothesized that the interaction of LIS1 and DCX is important to proper microtubule function in the developing cerebral cortex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11001923" 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="#26" class="mim-tip-reference" title="Shmueli, O., Gdalyahu, A., Sorokina, K., Nevo, E., Avivi, A., Reiner, O. <strong>DCX in PC12 cells: CREB-mediated transcription and neurite outgrowth.</strong> Hum. Molec. Genet. 10: 1061-1070, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11331616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11331616</a>] [<a href="https://doi.org/10.1093/hmg/10.10.1061" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11331616">Shmueli et al. (2001)</a> found that overexpression of DCX in PC12 cells resulted in stabilization of microtubules and inhibition of neurite outgrowth during nerve growth factor (NGF; <a href="/entry/162030">162030</a>)-induced differentiation. However, neurite length was increased when differentiation was induced by epidermal growth factor (<a href="/entry/131530">131530</a>) and forskolin or by dibutyryl-cAMP. Furthermore, CREB (<a href="/entry/123810">123810</a>)-mediated transcription was downregulated, supporting the notion that cytoskeletal regulatory proteins can affect the transcriptional state of a cell. Overexpression of a mutation (S47R; <a href="#0007">300121.0007</a>) found in a lissencephaly patient completely blocked neurite outgrowth. The authors concluded that microtubule stabilization is a key factor, but not the only one, in controlling neurite extension. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11331616" 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>Phosphorylation of DCX is developmentally regulated in brain, and phosphorylation corresponds to expression of p35 (CDK5R1; <a href="/entry/603460">603460</a>), the major activating subunit for CDK5 (<a href="/entry/123831">123831</a>). <a href="#28" class="mim-tip-reference" title="Tanaka, T., Serneo, F. F., Tseng, H.-C., Kulkarni, A. B., Tsai, L.-H., Gleeson, J. G. <strong>Cdk5 phosphorylation of doublecortin Ser297 regulates its effect on neuronal migration.</strong> Neuron 41: 215-227, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14741103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14741103</a>] [<a href="https://doi.org/10.1016/s0896-6273(03)00852-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14741103">Tanaka et al. (2004)</a> found that Dcx was phosphorylated on ser297 by Cdk5 during mouse brain development. Phosphorylation lowered the affinity of Dcx to microtubules in vitro, reduced its effect on polymerization, and displaced it from microtubules in cultured neurons. In addition, mutation of ser297 blocked the effect of Dcx on neuron migration in a fashion similar to inhibition of Cdk5 activity. <a href="#28" class="mim-tip-reference" title="Tanaka, T., Serneo, F. F., Tseng, H.-C., Kulkarni, A. B., Tsai, L.-H., Gleeson, J. G. <strong>Cdk5 phosphorylation of doublecortin Ser297 regulates its effect on neuronal migration.</strong> Neuron 41: 215-227, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14741103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14741103</a>] [<a href="https://doi.org/10.1016/s0896-6273(03)00852-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14741103">Tanaka et al. (2004)</a> concluded that DCX phosphorylation by CDK5 regulates its actions on migrating neurons through an effect on microtubules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14741103" 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="#20" class="mim-tip-reference" title="Mauffrey, P., Tchitchek, N., Barroca, V., Bemelmans, A., Firlej, V., Allory, Y., Romeo, PH., Magnon, C. <strong>Progenitors from the central nervous system drive neurogenesis in cancer.</strong> Nature 569: 672-678, 2019. Note: Erratum: Nature 577: E10, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31092925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31092925</a>] [<a href="https://doi.org/10.1038/s41586-019-1219-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31092925">Mauffrey et al. (2019)</a> showed that neural progenitors from the central nervous system that express DCX infiltrate prostate tumors and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX+ neural progenitors in the subventricular zone, a neurogenic area of the central nervous system, were associated with disruption of the blood-brain barrier, and with the egress of DCX+ cells into the circulation. These cells then infiltrated and resided in the tumor, and could generate new adrenergic neurons. Selective genetic depletion of DCX+ cells inhibited the early phases of tumor development in mouse models of prostate cancer, whereas transplantation of DCX+ neural progenitors promoted tumor growth and metastasis. In humans, the density of DCX+ neural progenitors was strongly associated with the aggressiveness and recurrence of prostate adenocarcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31092925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected individuals from 3 unrelated families with LISX or subcortical laminar (band) heterotopia (SCLH or SBH, see <a href="/entry/300067">300067</a>) and in a girl with subcortical laminar heterotopia and pachygyria, <a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">des Portes et al. (1998)</a> identified mutations in the DCX gene (<a href="#0001">300121.0001</a>-<a href="#0004">300121.0004</a>). <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> also identified several mutations in the DCX gene (<a href="#0002">300121.0002</a>; <a href="#0005">300121.0005</a>-<a href="#0010">300121.0010</a>) in affected individuals from unrelated families with LISX or subcortical laminar heterotopia and in females with sporadic subcortical laminar heterotopia, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9489699+9489700" 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="des Portes, V., Francis, F., Pinard, J.-M., Desguerre, I., Moutard, M.-L., Snoeck, I., Meiners, L. C., Capron, F., Cusmai, R., Ricci, S., Motte, J., Echenne, B., Ponsot, G., Dulac, O., Chelly, J., Beldjord, C. <strong>Doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH).</strong> Hum. Molec. Genet. 7: 1063-1070, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618162</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1063" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618162">Des Portes et al. (1998)</a> identified mutations in the DCX gene in 10 of 11 unrelated females with subcortical laminar heterotopia. The sequence differences included nonsense, splice site, and missense mutations, and these were found throughout the gene. The absence of phenotype-genotype correlations suggested that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618162" 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="#27" class="mim-tip-reference" title="Sossey-Alaoui, K., Hartung, A. J., Guerrini, R., Manchester, D. K., Posar, A., Puche-Mira, A., Andermann, E., Dobyns, W. B., Srivastava, A. K. <strong>Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca(2+)-dependent signaling protein which is mutated in human X-linked neuronal migration defects.</strong> Hum. Molec. Genet. 7: 1327-1332, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9668176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9668176</a>] [<a href="https://doi.org/10.1093/hmg/7.8.1327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9668176">Sossey-Alaoui et al. (1998)</a> identified 4 novel missense mutations in the DCX gene: 1 familial mutation with LISX in a male and subcortical band heterotopia in the carrier females, 1 de novo mutation in an SBH female, and 2 mutations in sporadic SBH female patients. They found that the DCX gene is expressed exclusively at a very high level in the adult frontal lobe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9668176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Gleeson, J. G., Minnerath, S. R., Fox, J. W., Allen, K. M., Luo, R. F., Hong, S. E., Berg, M. J., Kuzniecky, R., Reitnauer, P. J., Borgatti, R., Puche Mira, A., Guerrini, R., and 14 others. <strong>Characterization of mutations in the gene doublecortin in patients with double cortex syndrome.</strong> Ann. Neurol. 45: 146-153, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9989615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9989615</a>] [<a href="https://doi.org/10.1002/1531-8249(199902)45:2<146::aid-ana3>3.0.co;2-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9989615">Gleeson et al. (1999)</a> identified mutations in the DCX gene in affected members of 8 families with SBH and in 18 (38%) of 47 patients with sporadic SBH. Most patients had single-amino acid substitutions, suggesting that patients with these mutations may have less of a reproductive disadvantage than do patients with protein truncation mutations. Significantly, single-amino acid substitutions were tightly clustered in 2 regions of the open reading frame, suggesting that these regions are critical for the function of the doublecortin protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9989615" 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="#22" class="mim-tip-reference" title="Pilz, D. T., Kuc, J., Matsumoto, N., Bodurtha, J., Bernadi, B., Tassinari, C. A., Dobyns, W. B., Ledbetter, D. H. <strong>Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1.</strong> Hum. Molec. Genet. 8: 1757-1760, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441340</a>] [<a href="https://doi.org/10.1093/hmg/8.9.1757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441340">Pilz et al. (1999)</a> demonstrated that mutations in either DCX or LIS1 cause SBH or mixed pachygyria (PCH)/SBH in males. They identified a missense mutation in exon 4 of the DCX gene (<a href="#0011">300121.0011</a>) in a boy with PCH/SBH, a different missense mutation in exon 4 of the DCX gene (<a href="#0012">300121.0012</a>) in a boy with mild SBH and in his mildly affected mother, and a missense mutation in exon 6 of the LIS1 gene (<a href="/entry/601545#0004">601545.0004</a>) in a boy with SBH (<a href="/entry/607432">607432</a>). The authors suggested that the missense mutations probably account for the less severe brain malformations, although other patients with missense mutations in the same exons have had diffuse lissencephaly. It appeared likely that the effect of the specific amino acid change on the protein determines the severity of the phenotype, with some mutations enabling residual protein function and allowing normal migration in a larger proportion of neurons. However, <a href="#22" class="mim-tip-reference" title="Pilz, D. T., Kuc, J., Matsumoto, N., Bodurtha, J., Bernadi, B., Tassinari, C. A., Dobyns, W. B., Ledbetter, D. H. <strong>Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1.</strong> Hum. Molec. Genet. 8: 1757-1760, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441340</a>] [<a href="https://doi.org/10.1093/hmg/8.9.1757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441340">Pilz et al. (1999)</a> expected that somatic mosaic mutations of both the LIS1 and DCX genes would prove to be important mechanisms in causing SBH in males. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441340" 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="#25" class="mim-tip-reference" title="Sapir, T., Horesh, D., Caspi, M., Atlas, R., Burgess, H. A., Wolf, S. G., Francis, F., Chelly, J., Elbaum, M., Pietrokovski, S., Reiner, O. <strong>Doublecortin mutations cluster in evolutionarily conserved functional domains.</strong> Hum. Molec. Genet. 9: 703-712, 2000. Note: Erratum: Hum. Molec. Genet. 9: 1461 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749977</a>] [<a href="https://doi.org/10.1093/hmg/9.5.703" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10749977">Sapir et al. (2000)</a> determined that 2 tandemly repeated 80-amino acid regions in the N terminus defined an evolutionarily conserved domain in the doublecortin protein. Missense mutations in the DCX gene fall within these conserved regions in a large majority of patients. Overexpression of some of the reported DCX mutations disrupted microtubules in COS-7 cells and/or changed their morphology; the most severe effect was observed with a tyrosine-to-histidine mutation at amino acid 125 (Y125H; <a href="#0003">300121.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10749977" 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="#11" class="mim-tip-reference" title="Gleeson, J. G., Minnerath, S., Kuzniecky, R. I., Dobyns, W. B., Young, I. D., Ross, M. E., Walsh, C. A. <strong>Somatic and germline mosaic mutations in the doublecortin gene are associated with variable phenotypes.</strong> Am. J. Hum. Genet. 67: 574-581, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10915612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10915612</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10915612[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/303043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10915612">Gleeson et al. (2000)</a> found evidence for somatic or germline mosaic DCX mutations in 6 of 20 patients with LISX/SCLH. Germline mosaicism was identified in 2 unaffected women, each with 2 affected children. Additionally, 1 affected male with SCLH was found to be a somatic mosaic, which presumably spared him from the more severe phenotype of lissencephaly. The high rate of mosaicism indicated that there may be a significant recurrence risk for these disorders in families at risk, even when the mother is unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10915612" 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 7 families with SBH/LISX, <a href="#1" class="mim-tip-reference" title="Aigner, L., Uyanik, G., Couillard-Despres, S., Ploetz, S., Wolff, G., Morris-Rosendahl, D., Martin, P., Eckel, U., Spranger, S., Otte, J., Woerle, H., Holthausen, H., Apheshiotis, N., Fluegel, D., Winkler, J. <strong>Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders.</strong> Neurology 60: 329-332, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552055</a>] [<a href="https://doi.org/10.1212/01.wnl.0000042091.90361.d2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12552055">Aigner et al. (2003)</a> identified 4 missense and 3 nonsense mutations in the DCX gene (see <a href="#0014">300121.0014</a>). There was a high rate of somatic mosaicism in male and female patients with incomplete penetrance of bilateral SBH, including nonpenetrance in a heterozygous woman. In 1 family, prenatal diagnosis was performed. The authors emphasized the variability of mutation expression and suggested that genetic analysis should include examination of several tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552055" 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="#29" class="mim-tip-reference" title="Vourc'h, P., Petit, E., Muh, J. P., Andres, C., Bienvenu, T., Beldjord, C., Chelly, J., Barthelemy, C. <strong>Exclusion of the coding sequence of the doublecortin gene as a susceptibility locus in autistic disorder. (Letter)</strong> Am. J. Med. Genet. 108: 164-167, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857568</a>] [<a href="https://doi.org/10.1002/ajmg.10210" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11857568">Vourc'h et al. (2002)</a> used DGGE to screen 59 patients with autism (17 females and 42 males) for mutations in the coding sequence of the doublecortin gene. No mutations were found. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857568" 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="Couillard-Despres, S., Uyanik, G., Ploetz, S., Karl, C., Koch, H., Winkler, J., Aigner, L. <strong>Mitotic impairment by doublecortin is diminished by doublecortin mutations found in patients.</strong> Neurogenetics 5: 83-93, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15045646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15045646</a>] [<a href="https://doi.org/10.1007/s10048-004-0176-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15045646">Couillard-Despres et al. (2004)</a> analyzed the impact of the arg192-to-trp (R192W; <a href="#0002">300121.0002</a>) and ala71-to-ser (A71S; <a href="#0014">300121.0014</a>) mutations in the DCX gene on COS-7 microtubule networks. Both mutant and wildtype DCX were able to bind and bundle microtubules; however, mutants possessed a decreased ability to perturb the mitotic machinery, to cause abnormal spindle orientation, and to impair mitotic progression. The magnitude of this decrease was found to be proportional to the severity of mutation-associated clinical symptoms, thereby providing a cell-based assay for the prognosis of DCX-associated neuronal migration disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15045646" 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>Using multiplex ligation-dependent probe amplification (MLPA) analysis, <a href="#21" class="mim-tip-reference" title="Mei, D., Parrini, E., Pasqualetti, M., Tortorella, G., Franzoni, E., Giussani, U., Marini, C., Migliarini, S., Guerrini, R. <strong>Multiplex ligation-dependent probe amplification detects DCX gene deletions in band heterotopia.</strong> Neurology 68: 446-450, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17283321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17283321</a>] [<a href="https://doi.org/10.1212/01.wnl.0000252945.75668.5d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17283321">Mei et al. (2007)</a> identified 3 large mutations in the DCX gene in 3 (27%) of 11 women with subcortical band heterotopia in whom DCX point mutations had not been identified by direct sequencing. The findings raised the percentage of DCX mutations from 52% to 65% in their series of 23 patients. <a href="#21" class="mim-tip-reference" title="Mei, D., Parrini, E., Pasqualetti, M., Tortorella, G., Franzoni, E., Giussani, U., Marini, C., Migliarini, S., Guerrini, R. <strong>Multiplex ligation-dependent probe amplification detects DCX gene deletions in band heterotopia.</strong> Neurology 68: 446-450, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17283321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17283321</a>] [<a href="https://doi.org/10.1212/01.wnl.0000252945.75668.5d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17283321">Mei et al. (2007)</a> concluded that deletions of DCX are an underascertained cause of SBH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17283321" 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="#17" class="mim-tip-reference" title="Leger, P.-L., Souville, I., Boddaert, N., Elie, C., Pinard, J. M., Plouin, P., Moutard, M. L., des Portes, V., Van Esch, H., Joriot, S., Renard, J. L., Chelly, J., Francis, F., Beldjord, C., Bahi-Buisson, N. <strong>The location of DCX mutations predicts malformation severity in X-linked lissencephaly.</strong> Neurogenetics 9: 277-285, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18685874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18685874</a>] [<a href="https://doi.org/10.1007/s10048-008-0141-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18685874">Leger et al. (2008)</a> identified 24 different mutations in the DCX gene, including 19 novel mutations, in 24 patients from 17 pedigrees with subcortical band heterotopia and in 9 patients with de novo mutations. Most (18 of 19) missense mutations were clustered in the N-DC and C-DC repeats that make up the microtubule-binding doublecortin domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18685874" 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>Using MLPA analysis, <a href="#13" class="mim-tip-reference" title="Haverfield, E. V., Whited, A. J., Petras, K. S., Dobyns, W. B., Das, S. <strong>Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia.</strong> Europ. J. Hum. Genet. 17: 911-918, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19050731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19050731</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19050731[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2008.213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19050731">Haverfield et al. (2009)</a> identified intragenic deletions of the DCX gene in 3 (33%) of 9 females with subcortical band heterotopia or SBH/pachygyria in whom no molecular defect had previously been identified. All had more severe involvement of the anterior region of the brain. No deletions or duplications of DCX were found in 13 females or 7 males with the more severe pachygyria or in 2 males with SBH/pachygyria in whom no molecular defect had previously been identified. <a href="#13" class="mim-tip-reference" title="Haverfield, E. V., Whited, A. J., Petras, K. S., Dobyns, W. B., Das, S. <strong>Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia.</strong> Europ. J. Hum. Genet. 17: 911-918, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19050731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19050731</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19050731[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2008.213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19050731">Haverfield et al. (2009)</a> suggested that genetic testing for SBH and pachygyria should include both mutation and deletion/duplication analysis of the DCX gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19050731" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Jamuar, S. S., Lam, A. N., Kircher, M., D'Gama, A. M., Wang, J., Barry, B. J., Zhang, X., Hill, R. S., Partlow, J. N., Rozzo, A., Servattalab, S., Mehta, B. K., and 20 others. <strong>Somatic mutations in cerebral cortical malformations.</strong> New Eng. J. Med. 371: 733-743, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25140959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25140959</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25140959[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa1314432" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25140959">Jamuar et al. (2014)</a> used a customized panel of known and candidate genes associated with brain malformations to apply targeted high-coverage sequencing (depth greater than or equal to 200x) to leukocyte-derived DNA samples from 158 individuals with brain malformations. Eight of these individuals carried somatic mutations; 6 of these 8 individuals had double cortex syndrome, with 3 of the 6 carrying mutations in DCX and the other 3 in LIS1 (<a href="/entry/601545">601545</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25140959" 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="#19" class="mim-tip-reference" title="Matsumoto, N., Leventer, R. J., Kuc, J. A., Mewborn, S. K., Dudlicek, L. L., Ramocki, M. B., Pilz, D. T., Mills, P. L., Das, S., Ross, M. E., Ledbetter, D. H., Dobyns, W. B. <strong>Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia.</strong> Europ. J. Hum. Genet. 9: 5-12, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175293</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11175293">Matsumoto et al. (2001)</a> identified 29 DCX mutations in 22 (85%) of 26 patients with sporadic SBH and in affected members of 11 pedigrees with LISX/SCLH. There were 19 missense mutations, 4 nonsense mutations, 4 small deletions, 1 large deletion, and 1 splice site mutation. The majority of missense mutations were located in the 2 evolutionarily conserved domains (<a href="#25" class="mim-tip-reference" title="Sapir, T., Horesh, D., Caspi, M., Atlas, R., Burgess, H. A., Wolf, S. G., Francis, F., Chelly, J., Elbaum, M., Pietrokovski, S., Reiner, O. <strong>Doublecortin mutations cluster in evolutionarily conserved functional domains.</strong> Hum. Molec. Genet. 9: 703-712, 2000. Note: Erratum: Hum. Molec. Genet. 9: 1461 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749977</a>] [<a href="https://doi.org/10.1093/hmg/9.5.703" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10749977">Sapir et al., 2000</a>). None of the missense mutations affected the Abl phosphorylation site in exon 4 or the serine/proline-rich region in exon 8. Many of the missense mutations involved the proposed microtubule-binding region in exon 4. Combined data with previous reports demonstrated that the prevalence of nonsense/truncation mutations of exons 4-6 was significantly different in sporadic (16/39) compared to familial (0/17) cases (p less than 0.005), as had been suggested by clinical experience showing a milder phenotype in familial compared with sporadic cases. When patients were divided into 3 subgroups based on cranial MRI scans, the results supported a correlation between genotype and band phenotype. Among patients with frontal thin bands, all were familial and all had missense mutations in exons 4-6. The prevalence of nonsense/truncation mutations was significantly different in the combined diffuse thick plus diffuse thin group (8/19) compared with the combined frontal thin plus normal MRI group (0/7) (p less than 0.05). X-inactivation studies did not identify a significant difference in X-inactivation skewing between SBH patients and normal controls. Indeed, in several multiplex families, individuals with similar phenotypes had markedly variable X-inactivation status. The authors noted that the contribution of X inactivation to the SBH phenotypes may be less than previously thought. Maternal germline mosaicism was identified in 1 family and suspected in another in which DNA from the mother was not available for study. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10749977+11175293" 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="#15" class="mim-tip-reference" title="Kato, M., Kanai, M., Soma, O., Takusa, Y., Kimura, T., Numakura, C., Matsuki, T., Nakamura, S., Hayasaka, K. <strong>Mutation of the doublecortin gene in male patients with double cortex syndrome: somatic mosaicism detected by hair root analysis.</strong> Ann. Neurol. 50: 547-551, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11601509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11601509</a>] [<a href="https://doi.org/10.1002/ana.1231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11601509">Kato et al. (2001)</a> reported 2 unrelated male patients with subcortical band heterotopia and 2 different heterozygous mutations in the DCX gene. The parents did not carry the mutations, indicating they were likely de novo. Hair root analysis in both patients revealed somatic mosaicism, suggesting that the mutations may have occurred during early postzygotic division. Although they did not estimate the ratio of mosaicism, <a href="#15" class="mim-tip-reference" title="Kato, M., Kanai, M., Soma, O., Takusa, Y., Kimura, T., Numakura, C., Matsuki, T., Nakamura, S., Hayasaka, K. <strong>Mutation of the doublecortin gene in male patients with double cortex syndrome: somatic mosaicism detected by hair root analysis.</strong> Ann. Neurol. 50: 547-551, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11601509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11601509</a>] [<a href="https://doi.org/10.1002/ana.1231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11601509">Kato et al. (2001)</a> commented that there is likely a genotype/phenotype severity correlation with increasing mutation load. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11601509" 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="#23" class="mim-tip-reference" title="Poolos, N. P., Das, S., Clark, G. D., Lardizabal, D., Noebels, J. L., Wyllie, E., Dobyns, W. B. <strong>Males with epilepsy, complete subcortical band heterotopia, and somatic mosaicism for DCX.</strong> Neurology 58: 1559-1562, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12034802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12034802</a>] [<a href="https://doi.org/10.1212/wnl.58.10.1559" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12034802">Poolos et al. (2002)</a> reported 2 male patients with complete subcortical band heterotopia, mild mental retardation, and seizures, resembling the female phenotype; both cases resulted from somatic mosaicism for DCX mutations. The authors noted that somatic mosaicism in males is the functional equivalent of X inactivation in females and thus most likely accounts for the milder phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12034802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In mice, <a href="#10" class="mim-tip-reference" title="Gleeson, J. G., Lin, P. T., Flanagan, L. A., Walsh, C. A. <strong>Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons.</strong> Neuron 23: 257-271, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10399933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10399933</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)80778-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10399933">Gleeson et al. (1999)</a> demonstrated that Dcx was expressed in migrating neurons throughout the central and peripheral nervous system during embryonic and postnatal development. Dcx protein localization overlapped with that of microtubules in cultured primary cortical neurons, and this overlapping expression was disrupted by microtubule depolymerization. Dcx coassembled with brain microtubules, and recombinant Dcx stimulated the polymerization of purified tubulin. Finally, overexpression of Dcx in heterologous cells led to a dramatic microtubule phenotype that was resistant to depolymerization. <a href="#10" class="mim-tip-reference" title="Gleeson, J. G., Lin, P. T., Flanagan, L. A., Walsh, C. A. <strong>Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons.</strong> Neuron 23: 257-271, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10399933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10399933</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)80778-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10399933">Gleeson et al. (1999)</a> concluded that Dcx directs neuronal migration by regulating the organization and stability of microtubules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10399933" 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>Using RNA interference (RNAi) of the DCX protein in utero, <a href="#2" class="mim-tip-reference" title="Bai, J., Ramos, R. L., Ackman, J. B., Thomas, A. M., Lee, R. V., LoTurco, J. J. <strong>RNAi reveals doublecortin is required for radial migration in rat neocortex.</strong> Nature Neurosci. 6: 1277-1283, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14625554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14625554</a>] [<a href="https://doi.org/10.1038/nn1153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14625554">Bai et al. (2003)</a> generated a rat model with very low levels of DCX protein expression. Inhibition of DCX expression in a cohort of migrating neocortical neurons disrupted radial migration of other migrating neurons. Many neurons prematurely stopped migrating to form subcortical band heterotopias within the intermediate zone and then the white matter, and many neurons migrated into inappropriate neocortical lamina within normotopic cortex. The authors suggested that DCX may be required for migrating cells to organize appropriate cytoskeletal responses to external signals that direct radial migration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14625554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a rat model of subcortical band heterotopia generated by in utero RNA interference of the Dcx gene, <a href="#18" class="mim-tip-reference" title="Manent, J.-B., Wang, Y., Chang, Y., Paramasivam, M., LoTurco, J. J. <strong>Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder.</strong> Nature Med. 15: 84-90, 2009. Note: Erratum: Nature Med. 17: 1521 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19098909/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19098909</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19098909[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.1897" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19098909">Manent et al. (2009)</a> found that aberrantly positioned neurons could be stimulated to migrate by conditional reexpression of Dcx after birth. Restarting migration in this way both reduced neocortical malformations and restored neuronal patterning. The capacity to reduce SBH continued into early postnatal development. Reexpression at postnatal day 0 (P0) led to marked SBH regression and restored neocortical lamination, whereas reexpression at P5 led to partial restoration of position and SBH regression, and reexpression at P10 led to partial recovery of position without SBH reduction. Intervention after birth also reduced the seizure threshold to a level similar to that of wildtype mice. The findings suggested that disorders of neuronal migration could potentially be treated by reengaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19098909" 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="#16" class="mim-tip-reference" title="Kerjan, G., Koizumi, H., Han, E. B., Dube, C. M., Djakovic, S. N., Patrick, G. N., Baram, T. Z., Heinemann, S. F., Gleeson, J. G. <strong>Mice lacking doublecortin and doublecortin-like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures.</strong> Proc. Nat. Acad. Sci. 106: 6766-6771, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19342486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19342486</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19342486[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0812687106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19342486">Kerjan et al. (2009)</a> found that heterozygous and homozygous Dclk2 (<a href="/entry/613166">613166</a>)-null mice were viable and fertile, had normal brain morphology, and no compensatory changes in expression of either Dcx or Dclk1 (<a href="/entry/604742">604742</a>). However, double-mutant Dcx/Dclk2-null mice showed poor survival, with only about 10% alive past 5 months of age. In addition, Dcx/Dclk2-null mice showed spontaneous seizures, often associated with behavioral arrest and forelimb myoclonus. These seizures were noted to start at about 3 weeks of age. EEG studies were consistent with a hippocampal focus. Histologic studies showed compounded dyslamination of the hippocampus, with a discontinuous CA1 field, neuronal displacement, and reduced packing density of the dentate granule neuron layer, resulting in increased thickness. The neocortex appeared to have normal organization. Dcx/Dclk2-null mice had reduced GABA inhibition secondary to overall network disorganization, as well as a decrease in dendritic arbors, which suggested an insufficient receptive field for inhibitory input. In situ hybridization studies in normal mice showed coexpression of Dcx and Dclk2 in the hippocampus during embryonic and postnatal stages. Comparative studies in other mutant mice suggested that the Dcx deficiency was the major contributor to lamination defects, and that Dcx and Dclk2 are functionally redundant. <a href="#16" class="mim-tip-reference" title="Kerjan, G., Koizumi, H., Han, E. B., Dube, C. M., Djakovic, S. N., Patrick, G. N., Baram, T. Z., Heinemann, S. F., Gleeson, J. G. <strong>Mice lacking doublecortin and doublecortin-like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures.</strong> Proc. Nat. Acad. Sci. 106: 6766-6771, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19342486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19342486</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19342486[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0812687106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19342486">Kerjan et al. (2009)</a> concluded that this mutant mouse model shows similarities to human X-linked lissencephaly (LISX1; <a href="/entry/300067">300067</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19342486" 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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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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</span>
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<strong>14 Selected Examples</a>):</strong>
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<a href="/allelicVariants/300121" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300121[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<a id="0001" class="mim-anchor"></a>
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<strong>.0001 LISSENCEPHALY, X-LINKED, 1</strong>
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SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
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DCX, ASP62ASN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894779 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894779;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012355 OR RCV000012356" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012355, RCV000012356" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012355...</a>
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<p>In a mother with X-linked subcortical laminar heterotopia and her son with lissencephaly (<a href="/entry/300067">300067</a>), <a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">des Portes et al. (1998)</a> identified a 599G-A transition in the DCX gene, resulting in an asp62-to-asn (D62N) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489699" 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="0002" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0002 LISSENCEPHALY, X-LINKED, 1</strong>
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<span class="mim-text-font">
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SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
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<span class="mim-text-font">
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DCX, ARG192TRP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894780 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894780;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012357 OR RCV000012358 OR RCV000145864 OR RCV000423650" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012357, RCV000012358, RCV000145864, RCV000423650" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012357...</a>
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</span>
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<span class="mim-text-font">
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<p>In affected members of a family with X-linked lissencephaly or subcortical laminar heterotopia (<a href="/entry/300067">300067</a>), <a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">des Portes et al. (1998)</a> identified a 989C-T transition in the DCX gene, resulting in an arg192-to-trp (R192W) substitution. <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> independently found the same mutation in a different family with the disorder. The substitution occurred in a CG hypermutable dinucleotide. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9489699+9489700" 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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<div>
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<a id="0003" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0003 LISSENCEPHALY, X-LINKED, 1</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<div style="float: left;">
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DCX, TYR125HIS
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</div>
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</span>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894781 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894781;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012359 OR RCV000012360" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012359, RCV000012360" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012359...</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with LISX/SCLH (<a href="/entry/300067">300067</a>), <a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">des Portes et al. (1998)</a> identified a 788T-C transition in the DCX gene, resulting in a tyr125-to-his (Y125H) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489699" 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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<br />
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<div>
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<div>
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<a id="0004" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0004 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<div style="float: left;">
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DCX, IVS4, G-A, +1
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1921403332 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1921403332;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1921403332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1921403332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001250735 OR RCV001844855" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001250735, RCV001844855" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001250735...</a>
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<span class="mim-text-font">
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<p>In a girl with subcortical laminar heterotopia (<a href="/entry/300067">300067</a>), <a href="#7" class="mim-tip-reference" title="des Portes, V., Pinard, J. M., Billuart, P., Vinet, M. C., Koulakoff, A., Carrie, A., Gelot, A., Dupuis, E., Motte, J., Berwald-Netter, Y., Catala, M., Kahn, A., Beldjord, C., Chelly, J. <strong>A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.</strong> Cell 92: 51-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489699</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489699">des Portes et al. (1998)</a> identified a G-to-A transition at the first nucleotide of intron 4 of the DCX gene, resulting in the skipping of exon 4 and a frameshift. In addition to subcortical laminar heterotopia, brain MRI showed extended agyria-pachygyria and complete agenesis of the corpus callosum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489699" 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="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 LISSENCEPHALY, X-LINKED, 1</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
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<span class="mim-text-font">
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DCX, ARG59LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs122457137 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs122457137;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs122457137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs122457137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012362 OR RCV000012363" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012362, RCV000012363" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012362...</a>
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</span>
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<span class="mim-text-font">
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<p>In affected members of a family with LISX/SCLH (<a href="/entry/300067">300067</a>), <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> found a C-to-A transversion in the DCX gene, resulting in an arg59-to-leu (R59L) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489700" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894782 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894782;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012364 OR RCV000012365 OR RCV001778649" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012364, RCV000012365, RCV001778649" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012364...</a>
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<p>In affected members of a family with LISX/SCLH (<a href="/entry/300067">300067</a>), <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> identified a C-to-G transversion in the DCX gene, resulting in a thr203-to-arg (T203R) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489700" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894783 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894783;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012366 OR RCV000012367 OR RCV001857334" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012366, RCV000012367, RCV001857334" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012366...</a>
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<p>In affected members of a family with LISX/SCLH (<a href="/entry/300067">300067</a>), <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> identified an A-to-C transversion in the DCX gene, resulting in a ser-to-arg (S47R) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489700" 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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<strong>.0008 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
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DCX, 2-BP INS, 36AG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569498597 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569498597;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1569498597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1569498597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012368" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012368" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012368</a>
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<p>In a female with subcortical laminar heterotopia (see <a href="/entry/300067">300067</a>), <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> found a 2-bp insertion (36insAG) in the DCX gene, resulting in a protein truncation at amino acid 24. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489700" 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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<strong>.0009 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
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DCX, 2-BP DEL, 684CT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1556401744 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1556401744;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1556401744" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1556401744" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012369 OR RCV000504055 OR RCV001575982" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012369, RCV000504055, RCV001575982" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012369...</a>
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<p>In a female with SCLH (see <a href="/entry/300067">300067</a>), <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> found a 2-bp deletion (684delCT) in the DCX gene, resulting in a protein truncation at amino acid 240. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489700" 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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<strong>.0010 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
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DCX, 2-BP DEL, 691CT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569497266 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569497266;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1569497266" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1569497266" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012370" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012370" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012370</a>
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<p>In a female with SCLH (see <a href="/entry/300067">300067</a>), <a href="#9" class="mim-tip-reference" title="Gleeson, J. G., Allen, K. M., Fox, J. W., Lamperti, E. D., Berkovic, S., Scheffer, I., Cooper, E. C., Dobyns, W. B., Minnerath, S. R., Ross, M. E., Walsh, C. A. <strong>Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.</strong> Cell 92: 63-72, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489700</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489700">Gleeson et al. (1998)</a> found a de novo 2-bp deletion (691delCT) in the DCX gene, resulting in a protein truncation at amino acid 240. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489700" 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="0011" class="mim-anchor"></a>
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<strong>.0011 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894784 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894784;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012371 OR RCV005089236" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012371, RCV005089236" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012371...</a>
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<p>Among a group of 11 male patients, 8 with subcortical band heterotopia (see <a href="/entry/300067">300067</a>) and 3 with a combination of frontal pachygyria (PCH) and posterior SBH, <a href="#22" class="mim-tip-reference" title="Pilz, D. T., Kuc, J., Matsumoto, N., Bodurtha, J., Bernadi, B., Tassinari, C. A., Dobyns, W. B., Ledbetter, D. H. <strong>Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1.</strong> Hum. Molec. Genet. 8: 1757-1760, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441340</a>] [<a href="https://doi.org/10.1093/hmg/8.9.1757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441340">Pilz et al. (1999)</a> identified a boy with mixed PCH/SBH who carried a de novo 233G-A transition in exon 4 of the DCX gene, resulting in an arg78-to-his (R78H) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441340" 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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<strong>.0012 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894785 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894785;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012372" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012372" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012372</a>
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<p>In a boy with mild subcortical band heterotopia (see <a href="/entry/300067">300067</a>) and in his mildly affected mother, <a href="#22" class="mim-tip-reference" title="Pilz, D. T., Kuc, J., Matsumoto, N., Bodurtha, J., Bernadi, B., Tassinari, C. A., Dobyns, W. B., Ledbetter, D. H. <strong>Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1.</strong> Hum. Molec. Genet. 8: 1757-1760, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441340</a>] [<a href="https://doi.org/10.1093/hmg/8.9.1757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10441340">Pilz et al. (1999)</a> identified a 264C-G transversion in exon 4 of the DCX gene, resulting in an arg89-to-gly (R89G) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441340" 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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<strong>.0013 LISSENCEPHALY, X-LINKED, 1</strong>
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SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
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DCX, ARG196HIS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs56030372 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs56030372;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs56030372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs56030372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012373 OR RCV000012374 OR RCV000145869 OR RCV001552573 OR RCV002274878 OR RCV002512983" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012373, RCV000012374, RCV000145869, RCV001552573, RCV002274878, RCV002512983" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012373...</a>
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<p>In affected members of a family with LISX/SCLH (<a href="/entry/300067">300067</a>), <a href="#5" class="mim-tip-reference" title="Demelas, L., Serra, G., Conti, M., Achene, A., Mastropaolo, C., Matsumoto, N., Dudlicek, L. L., Mills, P. L., Dobyns, W. B., Ledbetter, D. H., Das, S. <strong>Incomplete penetrance with normal MRI in a woman with germline mutation of the DCX gene.</strong> Neurology 57: 327-330, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11468322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11468322</a>] [<a href="https://doi.org/10.1212/wnl.57.2.327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11468322">Demelas et al. (2001)</a> identified a 587G-A mutation in exon 5 of the DCX gene, resulting in an arg196-to-his (R196H) substitution. Three brothers showed microcephaly, mild to moderate developmental delay, seizures and other neurologic abnormalities, as well as classic lissencephaly on MRI. The mother and grandmother were shown to be carriers of the mutation, and the mother had a normal phenotype, including a normal MRI. After excluding mosaicism and skewed X inactivation, <a href="#5" class="mim-tip-reference" title="Demelas, L., Serra, G., Conti, M., Achene, A., Mastropaolo, C., Matsumoto, N., Dudlicek, L. L., Mills, P. L., Dobyns, W. B., Ledbetter, D. H., Das, S. <strong>Incomplete penetrance with normal MRI in a woman with germline mutation of the DCX gene.</strong> Neurology 57: 327-330, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11468322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11468322</a>] [<a href="https://doi.org/10.1212/wnl.57.2.327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11468322">Demelas et al. (2001)</a> concluded that the mother represented a rare case of nonpenetrance of a DCX mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11468322" 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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<strong>.0014 LISSENCEPHALY, X-LINKED, 1</strong>
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SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
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DCX, ALA71SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894786 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894786;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs104894786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000012375 OR RCV000012376" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012375, RCV000012376" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012375...</a>
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<p>In affected members of a family presenting typical features of LISX/SCLH (<a href="/entry/300067">300067</a>), <a href="#1" class="mim-tip-reference" title="Aigner, L., Uyanik, G., Couillard-Despres, S., Ploetz, S., Wolff, G., Morris-Rosendahl, D., Martin, P., Eckel, U., Spranger, S., Otte, J., Woerle, H., Holthausen, H., Apheshiotis, N., Fluegel, D., Winkler, J. <strong>Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders.</strong> Neurology 60: 329-332, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552055</a>] [<a href="https://doi.org/10.1212/01.wnl.0000042091.90361.d2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12552055">Aigner et al. (2003)</a> identified an ala71-to-ser (A71S) mutation in the DCX gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552055" 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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<strong>REFERENCES</strong>
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Aigner, L., Uyanik, G., Couillard-Despres, S., Ploetz, S., Wolff, G., Morris-Rosendahl, D., Martin, P., Eckel, U., Spranger, S., Otte, J., Woerle, H., Holthausen, H., Apheshiotis, N., Fluegel, D., Winkler, J.
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<strong>Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders.</strong>
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Neurology 60: 329-332, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12552055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12552055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12552055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000042091.90361.d2" target="_blank">Full Text</a>]
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Bai, J., Ramos, R. L., Ackman, J. B., Thomas, A. M., Lee, R. V., LoTurco, J. J.
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<strong>RNAi reveals doublecortin is required for radial migration in rat neocortex.</strong>
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Nature Neurosci. 6: 1277-1283, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14625554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14625554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14625554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nn1153" target="_blank">Full Text</a>]
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Caspi, M., Atlas, R., Kantor, A., Sapir, T., Reiner, O.
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<strong>Interaction between LIS1 and doublecortin, two lissencephaly gene products.</strong>
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Hum. Molec. Genet. 9: 2205-2213, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11001923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11001923</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11001923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/oxfordjournals.hmg.a018911" target="_blank">Full Text</a>]
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Couillard-Despres, S., Uyanik, G., Ploetz, S., Karl, C., Koch, H., Winkler, J., Aigner, L.
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<strong>Mitotic impairment by doublecortin is diminished by doublecortin mutations found in patients.</strong>
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Neurogenetics 5: 83-93, 2004.
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[<a href="https://doi.org/10.1007/s10048-004-0176-1" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/wnl.57.2.327" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/7.7.1063" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(00)80898-3" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.34.3.177" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(00)80899-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0896-6273(00)80778-3" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/303043" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/1531-8249(199902)45:2<146::aid-ana3>3.0.co;2-n" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ejhg.2008.213" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJMoa1314432" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.1231" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.0812687106" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s10048-008-0141-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nm.1897" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5200548" target="_blank">Full Text</a>]
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<a id="20" class="mim-anchor"></a>
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<a id="Mauffrey2019" class="mim-anchor"></a>
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Mauffrey, P., Tchitchek, N., Barroca, V., Bemelmans, A., Firlej, V., Allory, Y., Romeo, PH., Magnon, C.
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<strong>Progenitors from the central nervous system drive neurogenesis in cancer.</strong>
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Nature 569: 672-678, 2019. Note: Erratum: Nature 577: E10, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31092925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31092925</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31092925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41586-019-1219-y" target="_blank">Full Text</a>]
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<a id="Mei2007" class="mim-anchor"></a>
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<p class="mim-text-font">
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Mei, D., Parrini, E., Pasqualetti, M., Tortorella, G., Franzoni, E., Giussani, U., Marini, C., Migliarini, S., Guerrini, R.
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<strong>Multiplex ligation-dependent probe amplification detects DCX gene deletions in band heterotopia.</strong>
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Neurology 68: 446-450, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17283321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17283321</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17283321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000252945.75668.5d" target="_blank">Full Text</a>]
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<a id="22" class="mim-anchor"></a>
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<a id="Pilz1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Pilz, D. T., Kuc, J., Matsumoto, N., Bodurtha, J., Bernadi, B., Tassinari, C. A., Dobyns, W. B., Ledbetter, D. H.
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<strong>Subcortical band heterotopia in rare affected males can be caused by missense mutations in DCX (XLIS) or LIS1.</strong>
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Hum. Molec. Genet. 8: 1757-1760, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10441340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10441340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10441340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/8.9.1757" target="_blank">Full Text</a>]
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<a id="23" class="mim-anchor"></a>
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<a id="Poolos2002" class="mim-anchor"></a>
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<p class="mim-text-font">
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Poolos, N. P., Das, S., Clark, G. D., Lardizabal, D., Noebels, J. L., Wyllie, E., Dobyns, W. B.
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<strong>Males with epilepsy, complete subcortical band heterotopia, and somatic mosaicism for DCX.</strong>
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Neurology 58: 1559-1562, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12034802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12034802</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12034802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.58.10.1559" target="_blank">Full Text</a>]
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<a id="Ross1997" class="mim-anchor"></a>
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Ross, M. E., Allen, K. M., Srivastava, A. K., Featherstone, T., Gleeson, J. G., Hirsch, B., Harding, B. N., Andermann, E., Abdullah, R., Berg, M., Czapansky-Bielman, D., Flanders, D. J., and 11 others.
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<strong>Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): a gene causing neuronal migration defects in human brain.</strong>
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Hum. Molec. Genet. 6: 555-562, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097958</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9097958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/6.4.555" target="_blank">Full Text</a>]
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<a id="Sapir2000" class="mim-anchor"></a>
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Sapir, T., Horesh, D., Caspi, M., Atlas, R., Burgess, H. A., Wolf, S. G., Francis, F., Chelly, J., Elbaum, M., Pietrokovski, S., Reiner, O.
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<strong>Doublecortin mutations cluster in evolutionarily conserved functional domains.</strong>
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Hum. Molec. Genet. 9: 703-712, 2000. Note: Erratum: Hum. Molec. Genet. 9: 1461 only, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749977</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10749977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/9.5.703" target="_blank">Full Text</a>]
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Shmueli, O., Gdalyahu, A., Sorokina, K., Nevo, E., Avivi, A., Reiner, O.
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<strong>DCX in PC12 cells: CREB-mediated transcription and neurite outgrowth.</strong>
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Hum. Molec. Genet. 10: 1061-1070, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11331616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11331616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11331616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/10.10.1061" target="_blank">Full Text</a>]
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<a id="Sossey-Alaoui1998" class="mim-anchor"></a>
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Sossey-Alaoui, K., Hartung, A. J., Guerrini, R., Manchester, D. K., Posar, A., Puche-Mira, A., Andermann, E., Dobyns, W. B., Srivastava, A. K.
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<strong>Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca(2+)-dependent signaling protein which is mutated in human X-linked neuronal migration defects.</strong>
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Hum. Molec. Genet. 7: 1327-1332, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9668176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9668176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9668176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/7.8.1327" target="_blank">Full Text</a>]
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<a id="Tanaka2004" class="mim-anchor"></a>
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Tanaka, T., Serneo, F. F., Tseng, H.-C., Kulkarni, A. B., Tsai, L.-H., Gleeson, J. G.
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<strong>Cdk5 phosphorylation of doublecortin Ser297 regulates its effect on neuronal migration.</strong>
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Neuron 41: 215-227, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14741103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14741103</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14741103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0896-6273(03)00852-3" target="_blank">Full Text</a>]
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Vourc'h, P., Petit, E., Muh, J. P., Andres, C., Bienvenu, T., Beldjord, C., Chelly, J., Barthelemy, C.
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<strong>Exclusion of the coding sequence of the doublecortin gene as a susceptibility locus in autistic disorder. (Letter)</strong>
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Am. J. Med. Genet. 108: 164-167, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857568</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.10210" target="_blank">Full Text</a>]
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Ada Hamosh - updated : 12/19/2019
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Ada Hamosh - updated : 09/02/2014<br>Cassandra L. Kniffin - updated : 7/19/2010<br>Cassandra L. Kniffin - updated : 12/21/2009<br>Cassandra L. Kniffin - updated : 2/12/2009<br>Cassandra L. Kniffin - updated : 10/28/2008<br>Cassandra L. Kniffin - reorganized : 4/21/2008<br>Cassandra L. Kniffin - updated : 4/17/2008<br>Patricia A. Hartz - updated : 2/8/2005<br>Victor A. McKusick - updated : 12/29/2004<br>Cassandra L. Kniffin - updated : 1/27/2004<br>Cassandra L. Kniffin - updated : 1/29/2003<br>Cassandra L. Kniffin - updated : 12/13/2002<br>Cassandra L. Kniffin - updated : 12/3/2002<br>Sonja A. Rasmussen - updated : 4/18/2002<br>George E. Tiller - updated : 10/10/2001<br>Michael B. Petersen - updated : 4/17/2001<br>George E. Tiller - updated : 12/14/2000<br>Victor A. McKusick - updated : 9/25/2000<br>George E. Tiller - updated : 4/18/2000<br>Victor A. McKusick - updated : 10/6/1999<br>Victor A. McKusick - updated : 10/1/1998<br>Victor A. McKusick - updated : 7/8/1998
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<span class="mim-text-font">
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Victor A. McKusick : 3/24/1998
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carol : 03/17/2020
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alopez : 12/19/2019<br>alopez : 09/02/2014<br>alopez : 12/16/2011<br>carol : 6/1/2011<br>wwang : 7/20/2010<br>ckniffin : 7/19/2010<br>wwang : 1/11/2010<br>ckniffin : 12/21/2009<br>wwang : 3/4/2009<br>ckniffin : 2/12/2009<br>wwang : 11/7/2008<br>ckniffin : 10/28/2008<br>carol : 4/21/2008<br>ckniffin : 4/17/2008<br>ckniffin : 11/19/2007<br>mgross : 2/8/2005<br>tkritzer : 1/3/2005<br>terry : 12/29/2004<br>tkritzer : 2/4/2004<br>ckniffin : 1/27/2004<br>tkritzer : 2/6/2003<br>tkritzer : 2/3/2003<br>ckniffin : 1/29/2003<br>ckniffin : 1/3/2003<br>cwells : 1/3/2003<br>ckniffin : 12/13/2002<br>cwells : 12/10/2002<br>ckniffin : 12/3/2002<br>carol : 4/19/2002<br>terry : 4/18/2002<br>cwells : 10/15/2001<br>cwells : 10/10/2001<br>carol : 4/17/2001<br>carol : 4/17/2001<br>carol : 12/23/2000<br>terry : 12/14/2000<br>mcapotos : 10/4/2000<br>terry : 9/25/2000<br>alopez : 4/18/2000<br>alopez : 4/18/2000<br>mgross : 11/1/1999<br>carol : 11/1/1999<br>mgross : 10/20/1999<br>mgross : 10/20/1999<br>terry : 10/6/1999<br>carol : 10/6/1998<br>terry : 10/1/1998<br>carol : 7/13/1998<br>terry : 7/8/1998<br>carol : 5/8/1998<br>carol : 3/30/1998<br>alopez : 3/24/1998
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<strong>*</strong> 300121
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<h3>
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DOUBLECORTIN; DCX
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DBCN
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: DCX</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: Xq23
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Genomic coordinates <span class="small">(GRCh38)</span> : X:111,293,779-111,412,192 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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Xq23
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</span>
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</td>
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<td>
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<span class="mim-font">
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Lissencephaly, X-linked
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</span>
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</td>
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<td>
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<span class="mim-font">
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300067
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</span>
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</td>
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<td>
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<span class="mim-font">
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X-linked
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Subcortical laminal heterotopia, X-linked
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</span>
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</td>
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<td>
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<span class="mim-font">
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300067
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</span>
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</td>
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<td>
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<span class="mim-font">
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X-linked
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By positional cloning of a brain-specific cDNA spanning an Xq22 breakpoint in a female with lissencephaly (LISX1; 300067), Gleeson et al. (1998) identified a gene, termed 'doublecortin' (DCX), that encodes a 360-residue protein with a predicted molecular mass of 40 kD and a putative Abl (189980) phosphorylation site. Northern blot analysis identified a 10-kb mRNA transcript with exclusive expression in fetal brain tissue and multiple splice variants. Independently, des Portes et al. (1998) used a YAC clone spanning the Xq22.3-q23 candidate LISX1 region identified by linkage studies (des Portes et al., 1997; Ross et al., 1997) to identify a cDNA corresponding to the DCX gene from a human fetal brain cDNA library. The authors also found a 9.5-kb mRNA transcript that was expressed only in fetal brain. Both Gleeson et al. (1998) and des Portes et al. (1998) predicted that doublecortin is required for neuronal migration and may be involved in signal transduction. </p><p>Des Portes et al. (1998) and Sossey-Alaoui et al. (1998) cloned the mouse Dcx gene. It encodes isoforms of a highly hydrophilic 40-kD protein, homologous to its human counterpart and containing several potential phosphorylation sites. Both human and mouse DCX proteins are homologous to a CNS protein containing a Ca(2+)/calmodulin kinase domain (DCAMKL1; 604742), suggesting that the DCX protein may belong to a novel class of intracellular proteins involved in neuronal migration through Ca(2+)-dependent signaling. </p><p>Leger et al. (2008) noted that the doublecortin domain consists of 2 evolutionarily conserved repeats, namely N-DC from amino acids 42 to 150 and C-DC from amino acids 171 to 275, that play a role in microtubule binding. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gleeson et al. (1998) and des Portes et al. (1998) determined that the DCX gene spans over 100 kb of DNA and contains 9 exons with 6 coding exons. The structure of the gene is unusual because only 16% of the sequence is coding, and the 3-prime untranslated region, which is contained in 1 exon, is 7.9 kb long. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using in situ hybridization, des Portes et al. (1998) observed DCX expression in human cerebral cortex at 21 weeks' gestational age. There was strong labeling in the ventricular zone and cortical plate and moderate labeling of the intermediate zone. In the intermediate zone, labeled cells were organized as oriented chains, suggestive of migrating neurons. Studies in mouse embryonic brain showed significant Dcx expression primarily in neuronal cells. </p><p>Caspi et al. (2000) demonstrated an interaction of the DCX gene with the LIS1 gene (PAFAH1B1; 601545) by coimmunoprecipitation, both in transiently transfected cells and in embryonic brain extracts. Immunofluorescence studies revealed that the 2 protein products colocalized in transfected cells and in primary neuronal cells. LIS1 and DCX enhanced tubulin polymerization in an additive fashion, as measured by a light-scattering assay in vitro. The authors hypothesized that the interaction of LIS1 and DCX is important to proper microtubule function in the developing cerebral cortex. </p><p>Shmueli et al. (2001) found that overexpression of DCX in PC12 cells resulted in stabilization of microtubules and inhibition of neurite outgrowth during nerve growth factor (NGF; 162030)-induced differentiation. However, neurite length was increased when differentiation was induced by epidermal growth factor (131530) and forskolin or by dibutyryl-cAMP. Furthermore, CREB (123810)-mediated transcription was downregulated, supporting the notion that cytoskeletal regulatory proteins can affect the transcriptional state of a cell. Overexpression of a mutation (S47R; 300121.0007) found in a lissencephaly patient completely blocked neurite outgrowth. The authors concluded that microtubule stabilization is a key factor, but not the only one, in controlling neurite extension. </p><p>Phosphorylation of DCX is developmentally regulated in brain, and phosphorylation corresponds to expression of p35 (CDK5R1; 603460), the major activating subunit for CDK5 (123831). Tanaka et al. (2004) found that Dcx was phosphorylated on ser297 by Cdk5 during mouse brain development. Phosphorylation lowered the affinity of Dcx to microtubules in vitro, reduced its effect on polymerization, and displaced it from microtubules in cultured neurons. In addition, mutation of ser297 blocked the effect of Dcx on neuron migration in a fashion similar to inhibition of Cdk5 activity. Tanaka et al. (2004) concluded that DCX phosphorylation by CDK5 regulates its actions on migrating neurons through an effect on microtubules. </p><p>Mauffrey et al. (2019) showed that neural progenitors from the central nervous system that express DCX infiltrate prostate tumors and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX+ neural progenitors in the subventricular zone, a neurogenic area of the central nervous system, were associated with disruption of the blood-brain barrier, and with the egress of DCX+ cells into the circulation. These cells then infiltrated and resided in the tumor, and could generate new adrenergic neurons. Selective genetic depletion of DCX+ cells inhibited the early phases of tumor development in mouse models of prostate cancer, whereas transplantation of DCX+ neural progenitors promoted tumor growth and metastasis. In humans, the density of DCX+ neural progenitors was strongly associated with the aggressiveness and recurrence of prostate adenocarcinoma. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In affected individuals from 3 unrelated families with LISX or subcortical laminar (band) heterotopia (SCLH or SBH, see 300067) and in a girl with subcortical laminar heterotopia and pachygyria, des Portes et al. (1998) identified mutations in the DCX gene (300121.0001-300121.0004). Gleeson et al. (1998) also identified several mutations in the DCX gene (300121.0002; 300121.0005-300121.0010) in affected individuals from unrelated families with LISX or subcortical laminar heterotopia and in females with sporadic subcortical laminar heterotopia, </p><p>Des Portes et al. (1998) identified mutations in the DCX gene in 10 of 11 unrelated females with subcortical laminar heterotopia. The sequence differences included nonsense, splice site, and missense mutations, and these were found throughout the gene. The absence of phenotype-genotype correlations suggested that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females. </p><p>Sossey-Alaoui et al. (1998) identified 4 novel missense mutations in the DCX gene: 1 familial mutation with LISX in a male and subcortical band heterotopia in the carrier females, 1 de novo mutation in an SBH female, and 2 mutations in sporadic SBH female patients. They found that the DCX gene is expressed exclusively at a very high level in the adult frontal lobe. </p><p>Gleeson et al. (1999) identified mutations in the DCX gene in affected members of 8 families with SBH and in 18 (38%) of 47 patients with sporadic SBH. Most patients had single-amino acid substitutions, suggesting that patients with these mutations may have less of a reproductive disadvantage than do patients with protein truncation mutations. Significantly, single-amino acid substitutions were tightly clustered in 2 regions of the open reading frame, suggesting that these regions are critical for the function of the doublecortin protein. </p><p>Pilz et al. (1999) demonstrated that mutations in either DCX or LIS1 cause SBH or mixed pachygyria (PCH)/SBH in males. They identified a missense mutation in exon 4 of the DCX gene (300121.0011) in a boy with PCH/SBH, a different missense mutation in exon 4 of the DCX gene (300121.0012) in a boy with mild SBH and in his mildly affected mother, and a missense mutation in exon 6 of the LIS1 gene (601545.0004) in a boy with SBH (607432). The authors suggested that the missense mutations probably account for the less severe brain malformations, although other patients with missense mutations in the same exons have had diffuse lissencephaly. It appeared likely that the effect of the specific amino acid change on the protein determines the severity of the phenotype, with some mutations enabling residual protein function and allowing normal migration in a larger proportion of neurons. However, Pilz et al. (1999) expected that somatic mosaic mutations of both the LIS1 and DCX genes would prove to be important mechanisms in causing SBH in males. </p><p>Sapir et al. (2000) determined that 2 tandemly repeated 80-amino acid regions in the N terminus defined an evolutionarily conserved domain in the doublecortin protein. Missense mutations in the DCX gene fall within these conserved regions in a large majority of patients. Overexpression of some of the reported DCX mutations disrupted microtubules in COS-7 cells and/or changed their morphology; the most severe effect was observed with a tyrosine-to-histidine mutation at amino acid 125 (Y125H; 300121.0003). </p><p>Gleeson et al. (2000) found evidence for somatic or germline mosaic DCX mutations in 6 of 20 patients with LISX/SCLH. Germline mosaicism was identified in 2 unaffected women, each with 2 affected children. Additionally, 1 affected male with SCLH was found to be a somatic mosaic, which presumably spared him from the more severe phenotype of lissencephaly. The high rate of mosaicism indicated that there may be a significant recurrence risk for these disorders in families at risk, even when the mother is unaffected. </p><p>In 7 families with SBH/LISX, Aigner et al. (2003) identified 4 missense and 3 nonsense mutations in the DCX gene (see 300121.0014). There was a high rate of somatic mosaicism in male and female patients with incomplete penetrance of bilateral SBH, including nonpenetrance in a heterozygous woman. In 1 family, prenatal diagnosis was performed. The authors emphasized the variability of mutation expression and suggested that genetic analysis should include examination of several tissues. </p><p>Vourc'h et al. (2002) used DGGE to screen 59 patients with autism (17 females and 42 males) for mutations in the coding sequence of the doublecortin gene. No mutations were found. </p><p>Couillard-Despres et al. (2004) analyzed the impact of the arg192-to-trp (R192W; 300121.0002) and ala71-to-ser (A71S; 300121.0014) mutations in the DCX gene on COS-7 microtubule networks. Both mutant and wildtype DCX were able to bind and bundle microtubules; however, mutants possessed a decreased ability to perturb the mitotic machinery, to cause abnormal spindle orientation, and to impair mitotic progression. The magnitude of this decrease was found to be proportional to the severity of mutation-associated clinical symptoms, thereby providing a cell-based assay for the prognosis of DCX-associated neuronal migration disorders. </p><p>Using multiplex ligation-dependent probe amplification (MLPA) analysis, Mei et al. (2007) identified 3 large mutations in the DCX gene in 3 (27%) of 11 women with subcortical band heterotopia in whom DCX point mutations had not been identified by direct sequencing. The findings raised the percentage of DCX mutations from 52% to 65% in their series of 23 patients. Mei et al. (2007) concluded that deletions of DCX are an underascertained cause of SBH. </p><p>Leger et al. (2008) identified 24 different mutations in the DCX gene, including 19 novel mutations, in 24 patients from 17 pedigrees with subcortical band heterotopia and in 9 patients with de novo mutations. Most (18 of 19) missense mutations were clustered in the N-DC and C-DC repeats that make up the microtubule-binding doublecortin domain. </p><p>Using MLPA analysis, Haverfield et al. (2009) identified intragenic deletions of the DCX gene in 3 (33%) of 9 females with subcortical band heterotopia or SBH/pachygyria in whom no molecular defect had previously been identified. All had more severe involvement of the anterior region of the brain. No deletions or duplications of DCX were found in 13 females or 7 males with the more severe pachygyria or in 2 males with SBH/pachygyria in whom no molecular defect had previously been identified. Haverfield et al. (2009) suggested that genetic testing for SBH and pachygyria should include both mutation and deletion/duplication analysis of the DCX gene. </p><p>Jamuar et al. (2014) used a customized panel of known and candidate genes associated with brain malformations to apply targeted high-coverage sequencing (depth greater than or equal to 200x) to leukocyte-derived DNA samples from 158 individuals with brain malformations. Eight of these individuals carried somatic mutations; 6 of these 8 individuals had double cortex syndrome, with 3 of the 6 carrying mutations in DCX and the other 3 in LIS1 (601545). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Matsumoto et al. (2001) identified 29 DCX mutations in 22 (85%) of 26 patients with sporadic SBH and in affected members of 11 pedigrees with LISX/SCLH. There were 19 missense mutations, 4 nonsense mutations, 4 small deletions, 1 large deletion, and 1 splice site mutation. The majority of missense mutations were located in the 2 evolutionarily conserved domains (Sapir et al., 2000). None of the missense mutations affected the Abl phosphorylation site in exon 4 or the serine/proline-rich region in exon 8. Many of the missense mutations involved the proposed microtubule-binding region in exon 4. Combined data with previous reports demonstrated that the prevalence of nonsense/truncation mutations of exons 4-6 was significantly different in sporadic (16/39) compared to familial (0/17) cases (p less than 0.005), as had been suggested by clinical experience showing a milder phenotype in familial compared with sporadic cases. When patients were divided into 3 subgroups based on cranial MRI scans, the results supported a correlation between genotype and band phenotype. Among patients with frontal thin bands, all were familial and all had missense mutations in exons 4-6. The prevalence of nonsense/truncation mutations was significantly different in the combined diffuse thick plus diffuse thin group (8/19) compared with the combined frontal thin plus normal MRI group (0/7) (p less than 0.05). X-inactivation studies did not identify a significant difference in X-inactivation skewing between SBH patients and normal controls. Indeed, in several multiplex families, individuals with similar phenotypes had markedly variable X-inactivation status. The authors noted that the contribution of X inactivation to the SBH phenotypes may be less than previously thought. Maternal germline mosaicism was identified in 1 family and suspected in another in which DNA from the mother was not available for study. </p><p>Kato et al. (2001) reported 2 unrelated male patients with subcortical band heterotopia and 2 different heterozygous mutations in the DCX gene. The parents did not carry the mutations, indicating they were likely de novo. Hair root analysis in both patients revealed somatic mosaicism, suggesting that the mutations may have occurred during early postzygotic division. Although they did not estimate the ratio of mosaicism, Kato et al. (2001) commented that there is likely a genotype/phenotype severity correlation with increasing mutation load. </p><p>Poolos et al. (2002) reported 2 male patients with complete subcortical band heterotopia, mild mental retardation, and seizures, resembling the female phenotype; both cases resulted from somatic mosaicism for DCX mutations. The authors noted that somatic mosaicism in males is the functional equivalent of X inactivation in females and thus most likely accounts for the milder phenotype. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In mice, Gleeson et al. (1999) demonstrated that Dcx was expressed in migrating neurons throughout the central and peripheral nervous system during embryonic and postnatal development. Dcx protein localization overlapped with that of microtubules in cultured primary cortical neurons, and this overlapping expression was disrupted by microtubule depolymerization. Dcx coassembled with brain microtubules, and recombinant Dcx stimulated the polymerization of purified tubulin. Finally, overexpression of Dcx in heterologous cells led to a dramatic microtubule phenotype that was resistant to depolymerization. Gleeson et al. (1999) concluded that Dcx directs neuronal migration by regulating the organization and stability of microtubules. </p><p>Using RNA interference (RNAi) of the DCX protein in utero, Bai et al. (2003) generated a rat model with very low levels of DCX protein expression. Inhibition of DCX expression in a cohort of migrating neocortical neurons disrupted radial migration of other migrating neurons. Many neurons prematurely stopped migrating to form subcortical band heterotopias within the intermediate zone and then the white matter, and many neurons migrated into inappropriate neocortical lamina within normotopic cortex. The authors suggested that DCX may be required for migrating cells to organize appropriate cytoskeletal responses to external signals that direct radial migration. </p><p>In a rat model of subcortical band heterotopia generated by in utero RNA interference of the Dcx gene, Manent et al. (2009) found that aberrantly positioned neurons could be stimulated to migrate by conditional reexpression of Dcx after birth. Restarting migration in this way both reduced neocortical malformations and restored neuronal patterning. The capacity to reduce SBH continued into early postnatal development. Reexpression at postnatal day 0 (P0) led to marked SBH regression and restored neocortical lamination, whereas reexpression at P5 led to partial restoration of position and SBH regression, and reexpression at P10 led to partial recovery of position without SBH reduction. Intervention after birth also reduced the seizure threshold to a level similar to that of wildtype mice. The findings suggested that disorders of neuronal migration could potentially be treated by reengaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk. </p><p>Kerjan et al. (2009) found that heterozygous and homozygous Dclk2 (613166)-null mice were viable and fertile, had normal brain morphology, and no compensatory changes in expression of either Dcx or Dclk1 (604742). However, double-mutant Dcx/Dclk2-null mice showed poor survival, with only about 10% alive past 5 months of age. In addition, Dcx/Dclk2-null mice showed spontaneous seizures, often associated with behavioral arrest and forelimb myoclonus. These seizures were noted to start at about 3 weeks of age. EEG studies were consistent with a hippocampal focus. Histologic studies showed compounded dyslamination of the hippocampus, with a discontinuous CA1 field, neuronal displacement, and reduced packing density of the dentate granule neuron layer, resulting in increased thickness. The neocortex appeared to have normal organization. Dcx/Dclk2-null mice had reduced GABA inhibition secondary to overall network disorganization, as well as a decrease in dendritic arbors, which suggested an insufficient receptive field for inhibitory input. In situ hybridization studies in normal mice showed coexpression of Dcx and Dclk2 in the hippocampus during embryonic and postnatal stages. Comparative studies in other mutant mice suggested that the Dcx deficiency was the major contributor to lamination defects, and that Dcx and Dclk2 are functionally redundant. Kerjan et al. (2009) concluded that this mutant mouse model shows similarities to human X-linked lissencephaly (LISX1; 300067). </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>14 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 LISSENCEPHALY, X-LINKED, 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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DCX, ASP62ASN
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<br />
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SNP: rs104894779,
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ClinVar: RCV000012355, RCV000012356
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a mother with X-linked subcortical laminar heterotopia and her son with lissencephaly (300067), des Portes et al. (1998) identified a 599G-A transition in the DCX gene, resulting in an asp62-to-asn (D62N) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0002 LISSENCEPHALY, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, ARG192TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894780,
|
|
|
|
|
|
|
|
ClinVar: RCV000012357, RCV000012358, RCV000145864, RCV000423650
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with X-linked lissencephaly or subcortical laminar heterotopia (300067), des Portes et al. (1998) identified a 989C-T transition in the DCX gene, resulting in an arg192-to-trp (R192W) substitution. Gleeson et al. (1998) independently found the same mutation in a different family with the disorder. The substitution occurred in a CG hypermutable dinucleotide. </p>
|
|
</span>
|
|
</div>
|
|
|
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|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 LISSENCEPHALY, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, TYR125HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894781,
|
|
|
|
|
|
|
|
ClinVar: RCV000012359, RCV000012360
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with LISX/SCLH (300067), des Portes et al. (1998) identified a 788T-C transition in the DCX gene, resulting in a tyr125-to-his (Y125H) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, IVS4, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1921403332,
|
|
|
|
|
|
|
|
ClinVar: RCV001250735, RCV001844855
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with subcortical laminar heterotopia (300067), des Portes et al. (1998) identified a G-to-A transition at the first nucleotide of intron 4 of the DCX gene, resulting in the skipping of exon 4 and a frameshift. In addition to subcortical laminar heterotopia, brain MRI showed extended agyria-pachygyria and complete agenesis of the corpus callosum. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 LISSENCEPHALY, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, ARG59LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs122457137,
|
|
|
|
|
|
|
|
ClinVar: RCV000012362, RCV000012363
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with LISX/SCLH (300067), Gleeson et al. (1998) found a C-to-A transversion in the DCX gene, resulting in an arg59-to-leu (R59L) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 LISSENCEPHALY, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, THR203ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894782,
|
|
|
|
|
|
|
|
ClinVar: RCV000012364, RCV000012365, RCV001778649
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with LISX/SCLH (300067), Gleeson et al. (1998) identified a C-to-G transversion in the DCX gene, resulting in a thr203-to-arg (T203R) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 LISSENCEPHALY, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, SER47ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894783,
|
|
|
|
|
|
|
|
ClinVar: RCV000012366, RCV000012367, RCV001857334
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with LISX/SCLH (300067), Gleeson et al. (1998) identified an A-to-C transversion in the DCX gene, resulting in a ser-to-arg (S47R) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, 2-BP INS, 36AG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569498597,
|
|
|
|
|
|
|
|
ClinVar: RCV000012368
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a female with subcortical laminar heterotopia (see 300067), Gleeson et al. (1998) found a 2-bp insertion (36insAG) in the DCX gene, resulting in a protein truncation at amino acid 24. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, 2-BP DEL, 684CT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1556401744,
|
|
|
|
|
|
|
|
ClinVar: RCV000012369, RCV000504055, RCV001575982
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a female with SCLH (see 300067), Gleeson et al. (1998) found a 2-bp deletion (684delCT) in the DCX gene, resulting in a protein truncation at amino acid 240. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, 2-BP DEL, 691CT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569497266,
|
|
|
|
|
|
|
|
ClinVar: RCV000012370
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a female with SCLH (see 300067), Gleeson et al. (1998) found a de novo 2-bp deletion (691delCT) in the DCX gene, resulting in a protein truncation at amino acid 240. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, ARG78HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894784,
|
|
|
|
|
|
|
|
ClinVar: RCV000012371, RCV005089236
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Among a group of 11 male patients, 8 with subcortical band heterotopia (see 300067) and 3 with a combination of frontal pachygyria (PCH) and posterior SBH, Pilz et al. (1999) identified a boy with mixed PCH/SBH who carried a de novo 233G-A transition in exon 4 of the DCX gene, resulting in an arg78-to-his (R78H) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, ARG89GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894785,
|
|
|
|
|
|
|
|
ClinVar: RCV000012372
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with mild subcortical band heterotopia (see 300067) and in his mildly affected mother, Pilz et al. (1999) identified a 264C-G transversion in exon 4 of the DCX gene, resulting in an arg89-to-gly (R89G) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 LISSENCEPHALY, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, ARG196HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs56030372,
|
|
|
|
|
|
|
|
ClinVar: RCV000012373, RCV000012374, RCV000145869, RCV001552573, RCV002274878, RCV002512983
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with LISX/SCLH (300067), Demelas et al. (2001) identified a 587G-A mutation in exon 5 of the DCX gene, resulting in an arg196-to-his (R196H) substitution. Three brothers showed microcephaly, mild to moderate developmental delay, seizures and other neurologic abnormalities, as well as classic lissencephaly on MRI. The mother and grandmother were shown to be carriers of the mutation, and the mother had a normal phenotype, including a normal MRI. After excluding mosaicism and skewed X inactivation, Demelas et al. (2001) concluded that the mother represented a rare case of nonpenetrance of a DCX mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 LISSENCEPHALY, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SUBCORTICAL LAMINAR HETEROTOPIA, X-LINKED, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCX, ALA71SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894786,
|
|
|
|
|
|
|
|
ClinVar: RCV000012375, RCV000012376
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family presenting typical features of LISX/SCLH (300067), Aigner et al. (2003) identified an ala71-to-ser (A71S) mutation in the DCX gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aigner, L., Uyanik, G., Couillard-Despres, S., Ploetz, S., Wolff, G., Morris-Rosendahl, D., Martin, P., Eckel, U., Spranger, S., Otte, J., Woerle, H., Holthausen, H., Apheshiotis, N., Fluegel, D., Winkler, J.
|
|
<strong>Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders.</strong>
|
|
Neurology 60: 329-332, 2003.
|
|
|
|
|
|
[PubMed: 12552055]
|
|
|
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Ada Hamosh - updated : 12/19/2019<br>Ada Hamosh - updated : 09/02/2014<br>Cassandra L. Kniffin - updated : 7/19/2010<br>Cassandra L. Kniffin - updated : 12/21/2009<br>Cassandra L. Kniffin - updated : 2/12/2009<br>Cassandra L. Kniffin - updated : 10/28/2008<br>Cassandra L. Kniffin - reorganized : 4/21/2008<br>Cassandra L. Kniffin - updated : 4/17/2008<br>Patricia A. Hartz - updated : 2/8/2005<br>Victor A. McKusick - updated : 12/29/2004<br>Cassandra L. Kniffin - updated : 1/27/2004<br>Cassandra L. Kniffin - updated : 1/29/2003<br>Cassandra L. Kniffin - updated : 12/13/2002<br>Cassandra L. Kniffin - updated : 12/3/2002<br>Sonja A. Rasmussen - updated : 4/18/2002<br>George E. Tiller - updated : 10/10/2001<br>Michael B. Petersen - updated : 4/17/2001<br>George E. Tiller - updated : 12/14/2000<br>Victor A. McKusick - updated : 9/25/2000<br>George E. Tiller - updated : 4/18/2000<br>Victor A. McKusick - updated : 10/6/1999<br>Victor A. McKusick - updated : 10/1/1998<br>Victor A. McKusick - updated : 7/8/1998
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Victor A. McKusick : 3/24/1998
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