5433 lines
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5433 lines
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Entry
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- *164770 - COLONY-STIMULATING FACTOR 1 RECEPTOR; CSF1R
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- OMIM
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</form>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*164770</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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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="#description">Description</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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</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="#cytogenetics">Cytogenetics</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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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/164770">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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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>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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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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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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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="panel-title">
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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=ENSG00000182578;t=ENST00000675795" 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=1436" 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=164770" 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="mimDna">
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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>
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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=ENSG00000182578;t=ENST00000675795" 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_001288705,NM_001349736,NM_001375320,NM_001375321,NM_005211,NR_109969,NR_164679" 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_001288705" 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=164770" 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=01269&isoform_id=01269_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/CSF1R" 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/29900,182522,442423,547770,553224,553292,1196434,1915976,1916754,27262659,28833091,62087218,76362060,119582153,119582154,125858971,194318482,194377498,194385850,218614095,311864062,330736924,569026720,1168720172,1769047515,1769047531" 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/P07333" 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=1436" 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=ENSG00000182578;t=ENST00000675795" 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=CSF1R" 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=CSF1R" 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+1436" 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/CSF1R" 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:1436" 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/1436" 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=chr5&hgg_gene=ENST00000675795.1&hgg_start=150053295&hgg_end=150113365&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>
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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://medlineplus.gov/genetics/gene/csf1r" 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=164770[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=164770[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/CSF1R/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/ENSG00000182578" 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.ebi.ac.uk/gwas/search?query=CSF1R" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=CSF1R" 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=CSF1R" 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=CSF1R&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/PA26936" 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:2433" 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/FBgn0032006.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:1339758" 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/CSF1R#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:1339758" 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/1436/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://www.orthodb.org/?ncbi=1436" 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><a href="https://wormbase.org/db/gene/gene?name=WBGene00006897;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-001205-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</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://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1436" 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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<div><a href="https://reactome.org/content/query?q=CSF1R&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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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 702427005<br />
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<strong>ICD10CM:</strong> G93.44<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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164770
|
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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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COLONY-STIMULATING FACTOR 1 RECEPTOR; CSF1R
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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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MCSFR<br />
|
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ONCOGENE FMS; FMS<br />
|
|
c-FMS<br />
|
|
CD115 ANTIGEN; CD115<br />
|
|
V-FMS MCDONOUGH FELINE SARCOMA VIRAL ONCOGENE HOMOLOG, FORMERLY
|
|
</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>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CSF1R" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CSF1R</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/5/661?start=-3&limit=10&highlight=661">5q32</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:150053295-150113365&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'})">5:150,053,295-150,113,365</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=618476,221820" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/661?start=-3&limit=10&highlight=661">
|
|
5q32
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Brain abnormalities, neurodegeneration, and dysosteosclerosis
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/618476"> 618476 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
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|
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</tr>
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|
|
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|
|
|
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|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Leukoencephalopathy, diffuse hereditary, with spheroids 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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<a href="/entry/221820"> 221820 </a>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p>The CSF1R gene, also known as c-FMS, encodes a tyrosine kinase growth factor receptor for colony-stimulating factor-1 (CSF1; <a href="/entry/120420">120420</a>), the macrophage- and monocyte-specific growth factor (<a href="#26" class="mim-tip-reference" title="Ridge, S. A., Worwood, M., Oscier, D., Jacobs, A., Padua, R. A. <strong>FMS mutations in myelodysplastic, leukemic, and normal subjects.</strong> Proc. Nat. Acad. Sci. 87: 1377-1380, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2406720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2406720</a>] [<a href="https://doi.org/10.1073/pnas.87.4.1377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2406720">Ridge et al., 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2406720" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The CSF1R gene is expressed in mononuclear phagocytes in the brain, known as microglia, which play a role in neuronal and brain development (summary by <a href="#7" class="mim-tip-reference" title="Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., Pollard, J. W. <strong>Absence of colony-stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits.</strong> PLoS One 6: e26317, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22046273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22046273</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22046273[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/10.1371/journal.pone.0026317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22046273">Erblich et al., 2011</a>), as well as in osteoclasts, which play an important role in bone mineralization (summary by <a href="#5" class="mim-tip-reference" title="Dai, X.-M., Zong, X.-H., Akhter, M. P., Stanley, E. R. <strong>Osteoclast deficiency results in disorganized matrix, reduced mineralization, and abnormal osteoblast behavior in developing bone.</strong> J. Bone Miner. Res. 19: 1441-1451, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15312244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15312244</a>] [<a href="https://doi.org/10.1359/JBMR.040514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15312244">Dai et al., 2004</a>). Phosphorylation of CSF1R triggered by ligand binding to the receptor activates multiple downstream kinase pathways, including PI3K (see <a href="/entry/171834">171834</a>), ERK1/2 (see <a href="/entry/176948">176948</a>), and JNK (see <a href="/entry/601158">601158</a>) (summary by <a href="#13" class="mim-tip-reference" title="Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others. <strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong> Am. J. Hum. Genet. 104: 925-935, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982609</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982609[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982609">Guo et al., 2019</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30982609+15312244+22046273" 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="#16" class="mim-tip-reference" title="How, G.-F., Venkatesh, B., Brenner, S. <strong>Conserved linkage between the puffer fish (Fugu rubripes) and human genes for platelet-derived growth factor receptor and macrophage colony-stimulating factor receptor.</strong> Genome Res. 6: 1185-1191, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8973913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8973913</a>] [<a href="https://doi.org/10.1101/gr.6.12.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8973913">How et al. (1996)</a> determined the sequences of the homologs of the human PDGFRB and CSF1R genes in the pufferfish (Fugu rubripes). Amino acid sequences of the Fugu and human PGFRB and CSF1R genes showed an overall homology of 45% and 39%, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8973913" 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 postnatal mouse brain, <a href="#7" class="mim-tip-reference" title="Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., Pollard, J. W. <strong>Absence of colony-stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits.</strong> PLoS One 6: e26317, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22046273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22046273</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22046273[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/10.1371/journal.pone.0026317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22046273">Erblich et al. (2011)</a> found that Csf1r is expressed in microglia, but not in neurons, astrocytes, or glial cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22046273" 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="mim-changed mim-change"><p><a href="#15" class="mim-tip-reference" title="Hampe, A., Shamoon, B.-M., Gobet, M., Sherr, C. J., Galibert, F. <strong>Nucleotide sequence and structural organization of the human FMS proto-oncogene.</strong> Oncogene Res. 4: 9-17, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2524025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2524025</a>]" pmid="2524025">Hampe et al. (1989)</a> demonstrated that the FMS gene contains 21 small exons interrupted by introns ranging in size from 6.3 kb to less than 0.1 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2524025" 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></div>
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<p><a href="#27" class="mim-tip-reference" title="Roberts, W. M., Look, A. T., Roussel, M. F., Sherr, C. J. <strong>Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes.</strong> Cell 55: 655-661, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2846185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2846185</a>] [<a href="https://doi.org/10.1016/0092-8674(88)90224-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2846185">Roberts et al. (1988)</a> demonstrated that a 5-prime untranslated exon of CSF1R is separated by a 26-kb intron from the 32-kb receptor coding sequences. Furthermore, the 3-prime end of the PDGFRB gene is located less than 0.5 kb upstream from this exon. The authors stated that the as yet unidentified CSF1R promoter/enhancer sequences may be confined to the nucleotides separating the 2 genes or could potentially lie within the PDGFR gene itself. Similarities in chromosomal localization, organization, and encoded amino acid sequences suggested that the CSF1R and PDGFR genes arose through duplication. The human homolog of the murine Fim2 proviral integration region corresponds to the 5-prime end of the FMS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2846185" 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>During sequence analysis of the first intron of the human FMS gene, <a href="#28" class="mim-tip-reference" title="Sapi, E., Flick, M. B., Kacinski, B. M. <strong>The first intron of human c-fms proto-oncogene contains a processed pseudogene (RPL7P) for ribosomal protein L7.</strong> Genomics 22: 641-645, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001978</a>] [<a href="https://doi.org/10.1006/geno.1994.1440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001978">Sapi et al. (1994)</a> identified an open reading frame encoding the ribosomal protein L7 (RPL7; <a href="/entry/604166">604166</a>). The sequence was identical to the full-length RPL7 cDNA sequence but lacked any recognizable introns, had a 30-bp poly(A) tail, and was bracketed by 2 perfect direct repeats of 14 bp. <a href="#28" class="mim-tip-reference" title="Sapi, E., Flick, M. B., Kacinski, B. M. <strong>The first intron of human c-fms proto-oncogene contains a processed pseudogene (RPL7P) for ribosomal protein L7.</strong> Genomics 22: 641-645, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001978</a>] [<a href="https://doi.org/10.1006/geno.1994.1440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8001978">Sapi et al. (1994)</a> demonstrated that despite the fact that the 5-prime flanking region of the RPL7 sequence contained a potential TATA box upstream of an intact open reading frame, the pseudogene (RPL7P) was not actively transcribed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The FMS oncogene was assigned to chromosome 5 by study of mouse-man somatic cell hybrids. The location was narrowed to 5q34 by the study of hamster-human cell hybrids with well-defined deletions of 5q (<a href="#11" class="mim-tip-reference" title="Groffen, J., Heisterkamp, N., Spurr, N. K., Dana, S. L., Wasmuth, J. J., Stephenson, J. R. <strong>Regional assignment of the human c-fms oncogene to band q34 of chromosome 5. (Abstract)</strong> Cytogenet. Cell Genet. 37: 484 only, 1984."None>Groffen et al., 1984</a>). The order on the long arm was found to be centromere--leuS--HEXB--EMTB--FMS--CHR. By in situ hybridization, <a href="#21" class="mim-tip-reference" title="Le Beau, M. M., Westbrook, C. A., Diaz, M. O., Larson, R. A., Rowley, J. D., Gasson, J. C., Golde, D. W., Sherr, C. J. <strong>Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders.</strong> Science 231: 984-987, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484837</a>] [<a href="https://doi.org/10.1126/science.3484837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3484837">Le Beau et al. (1986)</a> assigned the FMS gene to chromosome 5q33.2 or 5q33.3 and the GMCSF (<a href="/entry/138960">138960</a>) gene to chromosome 5q23-q31. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3484837" 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="Roberts, W. M., Look, A. T., Roussel, M. F., Sherr, C. J. <strong>Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes.</strong> Cell 55: 655-661, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2846185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2846185</a>] [<a href="https://doi.org/10.1016/0092-8674(88)90224-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2846185">Roberts et al. (1988)</a> demonstrated that the CSF1R gene and the PDGFR1 (<a href="/entry/173410">173410</a>) gene are physically associated in a head-to-tail array, with less than 500 bp between the polyadenylation signal of the PDGFRB gene and the transcription start point of the CSF1R gene. By pulsed field gel electrophoresis, <a href="#6" class="mim-tip-reference" title="Eccles, M. R. <strong>Genes encoding the platelet-derived growth factor (PDGF) receptor and colony-stimulating factor 1 (CSF-1) receptor are physically associated in mice as in humans.</strong> Gene 108: 285-288, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1660841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1660841</a>] [<a href="https://doi.org/10.1016/0378-1119(91)90447-j" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1660841">Eccles (1991)</a> demonstrated that the same is true in the mouse where a 425-kb fragment hybridizes with the 3-prime end of PDGFR1 and the 5-prime end of CSF1R. In Fugu (pufferfish), <a href="#16" class="mim-tip-reference" title="How, G.-F., Venkatesh, B., Brenner, S. <strong>Conserved linkage between the puffer fish (Fugu rubripes) and human genes for platelet-derived growth factor receptor and macrophage colony-stimulating factor receptor.</strong> Genome Res. 6: 1185-1191, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8973913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8973913</a>] [<a href="https://doi.org/10.1101/gr.6.12.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8973913">How et al. (1996)</a> demonstrated that the 2 genes are closely linked in a head-to-tail array with 2.2 kb of intergenic sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8973913+2846185+1660841" 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>Three mouse genomic domains, Fim1, Fim2, and Fim3, have been described as proviral integration regions frequently involved in the early stages of myeloblastic leukemogenesis induced in vivo or in vitro by the Friend murine leukemia virus. Fim2 has been identified as the 5-prime end of the Fms protooncogene. Van Cong et al. (<a href="#31" class="mim-tip-reference" title="Van Cong, N., Fichelson, S., Sola, B., Gross, M. S., Jegou-Foubert, C., Bordereaux, D., Gisselbrecht, S., Tambourin, P. E., Frezal, J. <strong>Assignment of Fim-2 (CSF1R) to chromosome 5q33 (in situ hybridization) and Fim-3 to chromosome 3 (somatic cell analysis) region 3q27 (in situ hybridization). (Abstract)</strong> Cytogenet. Cell Genet. 46: 670 only, 1987."None>1987</a>, <a href="#30" class="mim-tip-reference" title="Van Cong, N., Fichelson, S., Gross, M. S., Sola, B., Bordereaux, D., de Tand, M. F., Guilhot, S., Gisselbrecht, S., Frezal, J., Tambourin, P. <strong>The human homologues of Fim1, Fim2/c-Fms, and Fim3, three retroviral integration regions involved in mouse myeloblastic leukemias, are respectively located on chromosomes 6p23, 5q33, and 3q27.</strong> Hum. Genet. 81: 257-263, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2921036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2921036</a>] [<a href="https://doi.org/10.1007/BF00279000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2921036">1989</a>) confirmed the localization of human FIM2/FMS on chromosome 5q33. By Southern blot analysis of DNA from human/rodent hybrids and by in situ hybridization, they mapped FIM1 to human chromosome 6p23-p22.3 and FIM3 to human chromosome 3q27. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2921036" 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="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 1/8/2013."None>Gross (2013)</a> mapped the CSF1R gene to chromosome 5q32 based on an alignment of the CSF1R sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC047521" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC047521</a>) with the genomic sequence (GRCh37).</p>
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<p><a href="#18" class="mim-tip-reference" title="Kondo, M., Scherer, D. C., Miyamoto, T., King, A. G., Akashi, K., Sugamura, K., Weissman, I. L. <strong>Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines.</strong> Nature 407: 383-386, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11014194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11014194</a>] [<a href="https://doi.org/10.1038/35030112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11014194">Kondo et al. (2000)</a> showed that a clonogenic common lymphoid progenitor, a bone marrow-resident cell that gives rise exclusively to lymphocytes (T, B, and natural killer cells), can be redirected to the myeloid lineage by stimulation through exogenously expressed interleukin-2 receptor (<a href="/entry/146710">146710</a>) and GMCSF receptor (<a href="/entry/138981">138981</a>, <a href="/entry/306250">306250</a>). Analysis of mutants of the beta-chain of the IL2 receptor revealed that the granulocyte and monocyte differentiation signals are triggered by different cytoplasmic domains, showing that the signaling pathways responsible for these unique developmental outcomes are separable. Finally, <a href="#18" class="mim-tip-reference" title="Kondo, M., Scherer, D. C., Miyamoto, T., King, A. G., Akashi, K., Sugamura, K., Weissman, I. L. <strong>Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines.</strong> Nature 407: 383-386, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11014194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11014194</a>] [<a href="https://doi.org/10.1038/35030112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11014194">Kondo et al. (2000)</a> showed that the endogenous myelomonocytic cytokine receptors for GM-CSF and macrophage colony-stimulating factor (CSF1R) are expressed at low to moderate levels on the more primitive hematopoietic stem cells, are absent on common lymphoid progenitors, and are upregulated after myeloid lineage induction by IL2 (<a href="/entry/147680">147680</a>). <a href="#18" class="mim-tip-reference" title="Kondo, M., Scherer, D. C., Miyamoto, T., King, A. G., Akashi, K., Sugamura, K., Weissman, I. L. <strong>Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines.</strong> Nature 407: 383-386, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11014194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11014194</a>] [<a href="https://doi.org/10.1038/35030112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11014194">Kondo et al. (2000)</a> concluded that cytokine signaling can regulate cell fate decisions and proposed that a critical step in lymphoid commitment is downregulation of cytokine receptors that drive myeloid cell development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11014194" 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="#8" class="mim-tip-reference" title="Faccio, R., Takeshita, S., Zallone, A., Ross, F. P., Teitelbaum, S. L. <strong>c-Fms and the alpha-V-beta-3 integrin collaborate during osteoclast differentiation.</strong> J. Clin. Invest. 111: 749-758, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618529</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618529[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/10.1172/JCI16924" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12618529">Faccio et al. (2003)</a> retrovirally transduced beta-3 integrin (ITGB3; <a href="/entry/173470">173470</a>) -/- osteoclast precursors with chimeric CSF1R constructs containing various cytoplasmic domain mutations and found that CSF1R tyr697 was required for normalization of osteoclastogenesis and ERK activation (see <a href="/entry/176948">176948</a>). Overexpression of FOS (<a href="/entry/164810">164810</a>) normalized the number of ITGB3 -/- osteoclasts in vitro but not their ability to resorb dentin. <a href="#8" class="mim-tip-reference" title="Faccio, R., Takeshita, S., Zallone, A., Ross, F. P., Teitelbaum, S. L. <strong>c-Fms and the alpha-V-beta-3 integrin collaborate during osteoclast differentiation.</strong> J. Clin. Invest. 111: 749-758, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618529</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618529[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/10.1172/JCI16924" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12618529">Faccio et al. (2003)</a> concluded that whereas CSF1R and alpha-V-beta-3 integrin collaborate in the osteoclastogenic process through shared activation of the ERK/FOS signaling pathway, the integrin is essential for matrix degradation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12618529" 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 fate mapping analysis, <a href="#9" class="mim-tip-reference" title="Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., Samokhvalov, I. M., Merad, M. <strong>Fate mapping analysis reveals that adult microglia derive from primitive macrophages.</strong> Science 330: 841-845, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20966214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20966214</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20966214[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/10.1126/science.1194637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20966214">Ginhoux et al. (2010)</a> showed that adult microglia derive from primitive macrophages. They showed that microglia develop in mice that lack colony-stimulating factor-1 (CSF1; <a href="/entry/120420">120420</a>) but are absent in Csf1 receptor-deficient mice. In vivo lineage tracing studies established that adult microglia derive from primitive myeloid progenitors expressing Runx1 (<a href="/entry/151385">151385</a>) that arise before embryonic day 8. <a href="#9" class="mim-tip-reference" title="Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., Samokhvalov, I. M., Merad, M. <strong>Fate mapping analysis reveals that adult microglia derive from primitive macrophages.</strong> Science 330: 841-845, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20966214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20966214</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20966214[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/10.1126/science.1194637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20966214">Ginhoux et al. (2010)</a> concluded that their results identified microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20966214" 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="#21" class="mim-tip-reference" title="Le Beau, M. M., Westbrook, C. A., Diaz, M. O., Larson, R. A., Rowley, J. D., Gasson, J. C., Golde, D. W., Sherr, C. J. <strong>Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders.</strong> Science 231: 984-987, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484837</a>] [<a href="https://doi.org/10.1126/science.3484837" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3484837">Le Beau et al. (1986)</a> found that the FMS and GM-CSF genes were both deleted from chromosome 5q- in bone marrow cells of 2 patients with refractory anemia and del(5)(q15-q33.3) (see chromosome 5q deletion syndrome; <a href="/entry/153550">153550</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3484837" 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="Morgan, R., Hecht, B. K., Sandberg, A. A., Hecht, F., Smith, S. D. <strong>Chromosome 5q35 breakpoint in malignant histiocytosis. (Letter)</strong> New Eng. J. Med. 314: 1322 only, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3702936/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3702936</a>] [<a href="https://doi.org/10.1056/nejm198605153142016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3702936">Morgan et al. (1986)</a> pointed out that a break at 5q35 has been found in several cases of malignant histiocytosis, a neoplastic process characterized by fever, progressive wasting, lymphadenopathy, hepatosplenomegaly, and the proliferation of atypical histiocytes at all stages of maturation with frequent phagocytic activity. They suggested that at the molecular level the change in band 5q35 may affect the FMS oncogene responsible for the receptor for mononuclear-phagocyte growth factor and thereby have a role in causing malignant histiocytosis. <a href="#3" class="mim-tip-reference" title="Benz-Lemoine, E., Brizard, A., Huret, J.-L., Babin, P., Guilhot, F., Couet, D., Tanzer, J. <strong>Malignant histiocytosis: a specific t(2;5)(p23;q35) translocation? Review of the literature.</strong> Blood 72: 1045-1047, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3416066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3416066</a>]" pmid="3416066">Benz-Lemoine et al. (1988)</a> also suggested that a breakpoint in 5q35 may be critical to the development of malignant histiocytosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3416066+3702936" 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="Boultwood, J., Rack, K., Kelly, S., Madden, J., Sakaguchi, A. Y., Wang, L.-M., Oscier, D. G., Buckle, V. J., Wainscoat, J. S. <strong>Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion.</strong> Proc. Nat. Acad. Sci. 88: 6176-6180, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1829836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1829836</a>] [<a href="https://doi.org/10.1073/pnas.88.14.6176" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1829836">Boultwood et al. (1991)</a> found loss of both CSF1R alleles in 10 patients with myelodysplasia and a 5q deletion; 6 were hemizygous and 4 were homozygous for CSF1R loss. <a href="#4" class="mim-tip-reference" title="Boultwood, J., Rack, K., Kelly, S., Madden, J., Sakaguchi, A. Y., Wang, L.-M., Oscier, D. G., Buckle, V. J., Wainscoat, J. S. <strong>Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion.</strong> Proc. Nat. Acad. Sci. 88: 6176-6180, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1829836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1829836</a>] [<a href="https://doi.org/10.1073/pnas.88.14.6176" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1829836">Boultwood et al. (1991)</a> suggested that loss of this hemopoietic growth factor receptor gene may also be important in the pathogenesis of myeloid leukemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1829836" 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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Among 110 patients with myelodysplastic and leukemic disorders, <a href="#26" class="mim-tip-reference" title="Ridge, S. A., Worwood, M., Oscier, D., Jacobs, A., Padua, R. A. <strong>FMS mutations in myelodysplastic, leukemic, and normal subjects.</strong> Proc. Nat. Acad. Sci. 87: 1377-1380, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2406720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2406720</a>] [<a href="https://doi.org/10.1073/pnas.87.4.1377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2406720">Ridge et al. (1990)</a> found somatic mutations in codon 969 of the CSF1R gene in 14 (12.7%) and in codon 301 in 2 (1.8%). The tyrosine residue at codon 969 was shown to be involved in a negative regulatory activity, which is disrupted by amino acid substitutions. Mutations at codon 301 lead to neoplastic transformation by ligand independence and constitutive tyrosine kinase activity of the receptor. Somatic mutations were most prevalent in chronic myelomonocytic leukemia (20%) and type M4 acute myeloblastic leukemia (23%), both of which are characterized by monocytic differentiation. One of 50 hematologically normal individuals had a 969C-T transition as a constitutional change, which may represent a predisposition to these particular malignancies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2406720" 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="Lamprecht, B., Walter, K., Kreher, S., Kumar, R., Hummel, M., Lenze, D., Kochert, K., Bouhlel, M. A., Richter, J., Soler, E., Stadhouders, R., Johrens, K., and 13 others. <strong>Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma.</strong> Nature Med. 16: 571-579, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20436485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20436485</a>] [<a href="https://doi.org/10.1038/nm.2129" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20436485">Lamprecht et al. (2010)</a> found that Reed-Sternberg cells in Hodgkin lymphoma (<a href="/entry/236000">236000</a>) demonstrated upregulation of CSF1R and CSF1 mRNA and constitutive activation of CSF1R, which correlated with increased proliferation of the Reed-Sternberg cells. Non-Hodgkin cell lines did not express either gene, suggesting that the expression in Reed-Sternberg cells was aberrant. Analysis of CSF1R transcripts in Reed-Sternberg cells showed use of an alternative transcription start site located about 6.2-kb upstream of the normal myeloid transcription start site: this sequence corresponded to a long terminal repeat (LTR) of the mammalian apparent LTR retrotransposon (MALR) THE1B family. LTRs derived from ancient retroviral infections have accumulated in the mammalian genome, and mammalian organisms have devised a number of surveillance mechanisms to silence these elements early in development, usually by DNA methylation. The LTR region was found to contain a number of putative binding sites for transcription factors (i.e., NFKB; <a href="/entry/164011">164011</a>) that were expressed in the Reed-Sternberg cells. Further studies indicated that the LTR is normally repressed by epigenetic methylation, and that Reed-Sternberg cells had lost this methylation. In addition, nearly all Reed-Sternberg cells studied had lost expression of the transcriptional repressor CBFA2T3 (<a href="/entry/603870">603870</a>). LTR-driven CSF1R transcripts were also found in anaplastic large cell lymphoma. <a href="#20" class="mim-tip-reference" title="Lamprecht, B., Walter, K., Kreher, S., Kumar, R., Hummel, M., Lenze, D., Kochert, K., Bouhlel, M. A., Richter, J., Soler, E., Stadhouders, R., Johrens, K., and 13 others. <strong>Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma.</strong> Nature Med. 16: 571-579, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20436485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20436485</a>] [<a href="https://doi.org/10.1038/nm.2129" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20436485">Lamprecht et al. (2010)</a> suggested that inhibition of CSF1R signaling may be of therapeutic value in Hodgkin lymphoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20436485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Hereditary Diffuse Leukoencephalopathy With Spheroids</em></strong></p><p>
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By linkage analysis followed by whole-exome sequencing of the family with hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>) reported by <a href="#29" class="mim-tip-reference" title="Swerdlow, R. H., Miller, B. B., Lopes, M. B. S., Mandell, J. W., Wooten, G. F., Damgaard, P., Manning, C., Fowler, M., Brashear, H. R. <strong>Autosomal dominant subcortical gliosis presenting as frontotemporal dementia.</strong> Neurology 72: 260-267, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19153373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19153373</a>] [<a href="https://doi.org/10.1212/01.wnl.0000339484.61490.a4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19153373">Swerdlow et al. (2009)</a>, <a href="#25" class="mim-tip-reference" title="Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M., Adamson, J., Kouri, N., and 26 others. <strong>Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.</strong> Nature Genet. 44: 200-205, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22197934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22197934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22197934[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/ng.1027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22197934">Rademakers et al. (2012)</a> identified a heterozygous mutation in the CSF1R gene (<a href="#0001">164770.0001</a>). Sequencing of this gene in 13 additional probands with HDLS identified a different heterozygous mutation in each (see, e.g., <a href="#0002">164770.0002</a>-<a href="#0005">164770.0005</a>). The mutations cosegregated with the disorder in all families for which DNA from multiple affected individuals was available, including the family reported by <a href="#2" class="mim-tip-reference" title="Baba, Y., Ghetti, B., Baker, M. C., Uitti, R. J., Hutton, M. L., Yamaguchi, K., Bird, T., Lin, W., DeLucia, M. W., Dickson, D. W., Wszolek, Z. K. <strong>Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred.</strong> Acta Neuropath. 111: 300-311, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16523341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16523341</a>] [<a href="https://doi.org/10.1007/s00401-006-0046-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16523341">Baba et al. (2006)</a>. The phenotype was characterized by adult-onset of a rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often died of dementia within 6 years of onset. Brain imaging showed patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes. In vitro functional expression studies of some of the missense mutations indicated that the mutant proteins did not show autophosphorylation, suggesting a defect in kinase activity that likely also affects downstream targets. The mutant proteins probably also act in a dominant-negative manner, since CSF1R assembles into homodimers. Overall, the findings indicated that a defect in microglial signaling and function resulting from CSF1R mutations can cause central nervous system degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19153373+16523341+22197934" 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 Japanese probands with HDLS, <a href="#19" class="mim-tip-reference" title="Konno, T., Tada, M., Tada, M., Koyama, A., Nozaki, H., Harigaya, Y., Nishimiya, J., Matsunaga, A., Yoshikura, N., Ishihara, K., Arakawa, M., Isami, A., and 11 others. <strong>Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS.</strong> Neurology 82: 139-148, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24336230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24336230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24336230[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/10.1212/WNL.0000000000000046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24336230">Konno et al. (2014)</a> identified 6 different heterozygous mutations in the CSF1R gene (see, e.g., <a href="#0004">164770.0004</a>; <a href="#0006">164770.0006</a>-<a href="#0008">164770.0008</a>). Two of the mutations resulted in truncated proteins, indicating that haploinsufficiency is sufficient to cause the disorder. In vitro functional expression studies in HEK293 cells showed that none of the mutant CSF1R proteins, including those caused by missense mutations, were able to autophosphorylate. However, coexpression of the mutants with wildtype did not suppress wildtype autophosphorylation, indicating that the mutations do not act in a dominant-negative manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24336230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Brain Abnormalities, Neurodegeneration, and Dysosteosclerosis</em></strong></p><p>
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In 6 patients from 3 unrelated families with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; <a href="/entry/618476">618476</a>), <a href="#13" class="mim-tip-reference" title="Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others. <strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong> Am. J. Hum. Genet. 104: 925-935, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982609</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982609[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982609">Guo et al. (2019)</a> identified homozygous or compound heterozygous mutations in the CSF1R gene (<a href="#0010">164770.0010</a>-<a href="#0014">164770.0014</a>). The mutations, which were found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Five different mutations were identified, including a nonsense and a missense variant in compound heterozygosity (see <a href="#0010">164770.0010</a>), an in-frame deletion and a deep intronic mutation in compound heterozygosity (see <a href="#0012">164770.0012</a>), and a deep intronic mutation in homozygosity (<a href="#0014">164770.0014</a>). In vitro functional expression studies of 3 of the variants showed that they were associated with decreased JNK (MAPK8; <a href="/entry/601158">601158</a>) phosphorylation, consistent with impaired function. The authors noted that the skeletal phenotype in these patients was not as severe as that observed in Csf1r-null mice, suggesting that some of the mutations likely result in hypomorphic alleles. However, the overall findings suggested that biallelic mutations that result in decreased CSF1R produce the skeletal phenotype, as heterozygous mutations that cause HDLS do not result in skeletal abnormalities. Moreover, <a href="#13" class="mim-tip-reference" title="Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others. <strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong> Am. J. Hum. Genet. 104: 925-935, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982609</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982609[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982609">Guo et al. (2019)</a> noted that the heterozygous parental carriers in their study did not have manifestations, suggesting that HDLS mutations likely act via a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982609" 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 2 unrelated patients with variable manifestations of BANDDOS, <a href="#24" class="mim-tip-reference" title="Oosterhof, N., Chang, I. J., Karimiani, E. G., Kuil, L. E., Jensen, D. M., Daza, R., Young, E., Astle, L., van der Linde, H. C., Shivaram, G. M., Demmers, J., Latimer, C. S., Keene, C. D., Loter, E., Maroofian, R., van Ham, T. J., Hevner, R. F., Bennett, J. T. <strong>Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia.</strong> Am. J. Hum. Genet. 104: 936-947, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982608[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982608">Oosterhof et al. (2019)</a> identified homozygous mutations in the CSF1R gene (<a href="#0015">164770.0015</a> and <a href="#0016">164770.0016</a>). Functional studies of the variants and studies of patient cells were not performed, but 1 was a splice site mutation (<a href="#0015">164770.0015</a>), predicted to result in a loss of function, and the other was a missense mutation (<a href="#0016">164770.0016</a>), predicted to have a hypomorphic effect. The patient with the missense mutation did not have apparent skeletal involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982608" 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="#5" class="mim-tip-reference" title="Dai, X.-M., Zong, X.-H., Akhter, M. P., Stanley, E. R. <strong>Osteoclast deficiency results in disorganized matrix, reduced mineralization, and abnormal osteoblast behavior in developing bone.</strong> J. Bone Miner. Res. 19: 1441-1451, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15312244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15312244</a>] [<a href="https://doi.org/10.1359/JBMR.040514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15312244">Dai et al. (2004)</a> found that Csf1r-null mice had frequent spontaneous fractures and decreased bone strength associated with an expanded epiphyseal chondrocyte region, poorly formed cortex with disorganized collagen fibrils, and a severely disturbed matrix structure. Since Csf1r is expressed in osteoclasts, the findings suggesting that mutant mice had a deficiency of osteoclast-mediated regulation of osteoblasts during formation of lamellar bone. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15312244" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Aikawa, Y., Katsumoto, T., Zhang, P., Shima, H., Shino, M., Terui, K., Ito, E., Ohno, H., Stanley, E. R., Singh, H., Tenen, D. G., Kitabayashi, I. <strong>PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. (Letter)</strong> Nature Med. 16: 580-585, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20418886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20418886</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20418886[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.2122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20418886">Aikawa et al. (2010)</a> found that mouse MOZ/TIF2 (see <a href="/entry/601408">601408</a>)-induced AML stem cells with high expression of Csf1r had increased leukemia initiating activity than AML stem cells with same amount of MOZ/TIF2 protein and low expression of Csf1r, when transplanted in irradiated mice. The high Csf1r expressing cells had the phenotype of granulocyte-macrophage progenitors and differentiated monocytes. In mice with leukemia due to these cells, treatment with a drug-inducible suicide gene targeting Csf1r-expressing cells resulted in curing of the leukemia for up to 6 months compared to controls. Induction of AML was suppressed in Csf1r-deficient mice, and Csf1r inhibitors slowed the progression of MOZ/TIF2-induced AML. Increased Csf1r expression was due mainly to the hematopoietic transcription factor PU.1 (<a href="/entry/165170">165170</a>), which was required for the initiation and maintenance of MOZ/TIF2-induced AML by increasing transcription of Csf1r. <a href="#1" class="mim-tip-reference" title="Aikawa, Y., Katsumoto, T., Zhang, P., Shima, H., Shino, M., Terui, K., Ito, E., Ohno, H., Stanley, E. R., Singh, H., Tenen, D. G., Kitabayashi, I. <strong>PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. (Letter)</strong> Nature Med. 16: 580-585, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20418886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20418886</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20418886[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.2122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20418886">Aikawa et al. (2010)</a> suggested that CSF1R is crucial for leukemia induced by MOZ fusion and indicated that targeting of PU.1 may be a therapeutic option. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20418886" 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="Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., Pollard, J. W. <strong>Absence of colony-stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits.</strong> PLoS One 6: e26317, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22046273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22046273</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22046273[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/10.1371/journal.pone.0026317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22046273">Erblich et al. (2011)</a> found that Csf1r-null mice had postnatal developmental brain abnormalities, including enlarged ventricles, periventricular changes, parenchymal volume loss, thinning of the cerebral cortex, and propensity to hydrocephalus. These changes were associated with severely decreased numbers of microglia in the brain. Mutant mice also died early. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22046273" 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="#24" class="mim-tip-reference" title="Oosterhof, N., Chang, I. J., Karimiani, E. G., Kuil, L. E., Jensen, D. M., Daza, R., Young, E., Astle, L., van der Linde, H. C., Shivaram, G. M., Demmers, J., Latimer, C. S., Keene, C. D., Loter, E., Maroofian, R., van Ham, T. J., Hevner, R. F., Bennett, J. T. <strong>Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia.</strong> Am. J. Hum. Genet. 104: 936-947, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982608[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982608">Oosterhof et al. (2019)</a> found that knockdown of the csf1r homologs in zebrafish resulted in lack of microglia in the brain. Vertebral arches in mutant animals were smaller compared to controls, which the authors suggested may recapitulate osteopetrosis. These abnormalities were associated with downregulation of cux1 (<a href="/entry/116896">116896</a>), a transcription factor present in neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982608" 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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<strong>16 Selected Examples</a>):</strong>
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<a href="/allelicVariants/164770" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=164770[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 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
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CSF1R, MET875THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs281860279 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281860279;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=rs281860279" 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=rs281860279" 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=RCV000022684 OR RCV005089298" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022684, RCV005089298" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022684...</a>
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<p>In affected members of a large family with hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>) originally reported by <a href="#29" class="mim-tip-reference" title="Swerdlow, R. H., Miller, B. B., Lopes, M. B. S., Mandell, J. W., Wooten, G. F., Damgaard, P., Manning, C., Fowler, M., Brashear, H. R. <strong>Autosomal dominant subcortical gliosis presenting as frontotemporal dementia.</strong> Neurology 72: 260-267, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19153373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19153373</a>] [<a href="https://doi.org/10.1212/01.wnl.0000339484.61490.a4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19153373">Swerdlow et al. (2009)</a>, <a href="#25" class="mim-tip-reference" title="Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M., Adamson, J., Kouri, N., and 26 others. <strong>Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.</strong> Nature Genet. 44: 200-205, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22197934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22197934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22197934[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/ng.1027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22197934">Rademakers et al. (2012)</a> identified a heterozygous 2624T-C transition in exon 20 of the CSF1R gene, resulting in a met875-to-thr (M875T) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. In vitro functional expression studies indicated that the mutant protein did not show autophosphorylation, suggesting a defect in kinase activity that likely also affects downstream targets. The mutant protein probably also acts in a dominant-negative manner, since CSF1R assembles into homodimers. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19153373+22197934" 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 class="mim-font">
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<strong>.0002 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
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CSF1R, GLU633LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs281860269 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281860269;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=rs281860269" 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=rs281860269" 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=RCV000022685 OR RCV001565941" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022685, RCV001565941" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022685...</a>
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<p>In affected members of a large family with hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>), originally reported by <a href="#2" class="mim-tip-reference" title="Baba, Y., Ghetti, B., Baker, M. C., Uitti, R. J., Hutton, M. L., Yamaguchi, K., Bird, T., Lin, W., DeLucia, M. W., Dickson, D. W., Wszolek, Z. K. <strong>Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred.</strong> Acta Neuropath. 111: 300-311, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16523341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16523341</a>] [<a href="https://doi.org/10.1007/s00401-006-0046-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16523341">Baba et al. (2006)</a>, <a href="#25" class="mim-tip-reference" title="Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M., Adamson, J., Kouri, N., and 26 others. <strong>Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.</strong> Nature Genet. 44: 200-205, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22197934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22197934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22197934[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/ng.1027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22197934">Rademakers et al. (2012)</a> identified a heterozygous 1897G-A transition in exon 14 of the CSF1R gene, resulting in a glu633-to-lys (E633K) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. In vitro functional expression studies indicated that the mutant protein did not show autophosphorylation, suggesting a defect in kinase activity that likely also affects downstream targets. The mutant protein probably also acts in a dominant-negative manner, since CSF1R assembles into homodimers. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16523341+22197934" 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="0003" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0003 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
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CSF1R, IVS12AS, A-G, -2
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs281860267 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281860267;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=rs281860267" 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=rs281860267" 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=RCV000022686" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022686" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022686</a>
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<p>In a pair of Norwegian monozygotic twins with hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>), <a href="#25" class="mim-tip-reference" title="Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M., Adamson, J., Kouri, N., and 26 others. <strong>Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.</strong> Nature Genet. 44: 200-205, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22197934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22197934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22197934[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/ng.1027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22197934">Rademakers et al. (2012)</a> identified a heterozygous de novo A-to-G transition in intron 12 of the CSF1R gene (1754-2A-G), resulting in the skipping of exon 13, the in-frame loss of 34 consecutive amino acids, and the insertion of an alanine residue. The mutation was predicted to result in the loss of multiple amino acids in the intracellular tyrosine kinase domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22197934" 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>.0004 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
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CSF1R, ILE794THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs281860274 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281860274;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs281860274?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs281860274" 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=rs281860274" 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=RCV000022687 OR RCV001090375 OR RCV003944835 OR RCV004795936" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022687, RCV001090375, RCV003944835, RCV004795936" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022687...</a>
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<p>In affected members of a family with hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>), <a href="#25" class="mim-tip-reference" title="Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M., Adamson, J., Kouri, N., and 26 others. <strong>Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.</strong> Nature Genet. 44: 200-205, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22197934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22197934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22197934[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/ng.1027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22197934">Rademakers et al. (2012)</a> identified a heterozygous 2381T-C transition in exon 18 of the CSF1R gene, resulting in an ile794-to-thr (I794T) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22197934" 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="#19" class="mim-tip-reference" title="Konno, T., Tada, M., Tada, M., Koyama, A., Nozaki, H., Harigaya, Y., Nishimiya, J., Matsunaga, A., Yoshikura, N., Ishihara, K., Arakawa, M., Isami, A., and 11 others. <strong>Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS.</strong> Neurology 82: 139-148, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24336230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24336230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24336230[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/10.1212/WNL.0000000000000046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24336230">Konno et al. (2014)</a> identified a heterozygous I794T substitution in 2 unrelated Japanese patients with HDLS. One had a family history of the disorder. In vitro functional expression assays in HEK293 cells showed that the mutant protein did not undergo autophosphorylation, but coexpression of the mutant with wildtype did not suppress wildtype autophosphorylation, indicating that the mutation does not act in a dominant-negative manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24336230" 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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<strong>.0005 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</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">rs387906662 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906662;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=rs387906662" 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=rs387906662" 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=RCV000022688" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022688" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022688</a>
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<p>In a woman with sporadic occurrence of hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>), <a href="#25" class="mim-tip-reference" title="Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M., Adamson, J., Kouri, N., and 26 others. <strong>Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.</strong> Nature Genet. 44: 200-205, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22197934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22197934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22197934[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/ng.1027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22197934">Rademakers et al. (2012)</a> identified a heterozygous 2509G-T transversion in exon 19 of the CSF1R gene, resulting in an asp837-to-tyr (D837Y) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. The patient was diagnosed clinically with a disorder resembling corticobasal syndrome, and was identified from a cohort of 93 patients with various neurologic symptoms. At age 43 years, she developed a gradual decline in expressing herself, word-finding, and performing motor tasks with her right hand and leg. About 2 years later, she had executive dysfunction, bradykinesia, hyperreflexia, apraxia, rigidity in the upper limbs, and spasticity in the lower limbs. There was rapid neurologic deterioration, and she died at age 50. Brain MRI showed localized white matter hyperintensities in the frontal and parietal white matter on T2-weighted images. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22197934" 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>.0006 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</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">rs587777245 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777245;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=rs587777245" 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=rs587777245" 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=RCV000106403" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000106403" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000106403</a>
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<p>In a Japanese woman with hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>), <a href="#19" class="mim-tip-reference" title="Konno, T., Tada, M., Tada, M., Koyama, A., Nozaki, H., Harigaya, Y., Nishimiya, J., Matsunaga, A., Yoshikura, N., Ishihara, K., Arakawa, M., Isami, A., and 11 others. <strong>Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS.</strong> Neurology 82: 139-148, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24336230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24336230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24336230[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/10.1212/WNL.0000000000000046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24336230">Konno et al. (2014)</a> identified a heterozygous 1-bp insertion (c.2060insT) in the CSF1R gene, resulting in a frameshift and premature termination (Ser688GlufsTer13). The mutation was not found in the dbSNP database or in 124 healthy controls. She had onset of the disorder at age 41 years and died at age 54; there was no family history of a similar disorder. The mutant protein was barely detectable in brain tissue from the patient, suggesting that it undergoes nonsense-mediated mRNA decay, resulting in haploinsufficiency. In vitro functional expression assays in HEK293 cells showed that the mutant protein did not undergo autophosphorylation, but coexpression of the mutant with wildtype did not suppress wildtype autophosphorylation, indicating that the mutation does not act in a dominant-negative manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24336230" 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>.0007 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</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">rs587777246 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777246;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=rs587777246" 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=rs587777246" 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=RCV000106404" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000106404" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000106404</a>
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<p>In a Japanese man with hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>), <a href="#19" class="mim-tip-reference" title="Konno, T., Tada, M., Tada, M., Koyama, A., Nozaki, H., Harigaya, Y., Nishimiya, J., Matsunaga, A., Yoshikura, N., Ishihara, K., Arakawa, M., Isami, A., and 11 others. <strong>Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS.</strong> Neurology 82: 139-148, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24336230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24336230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24336230[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/10.1212/WNL.0000000000000046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24336230">Konno et al. (2014)</a> identified a heterozygous G-to-T transversion in intron 18 of the CSF1R gene (c.2442+1G-T), resulting in a splice site mutation. Patient tissue showed 3 aberrant splice variants with skipped exon 18, all resulting in truncated proteins. Western blot analysis of patient brain tissue showed markedly decreased expression of the full-length protein. In vitro functional expression assays in HEK293 cells showed that the mutant protein did not undergo autophosphorylation, but coexpression of the mutant with wildtype did not suppress wildtype autophosphorylation, indicating that the mutation does not act in a dominant-negative manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24336230" 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 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
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CSF1R, ALA781GLU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777247 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777247;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=rs587777247" 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=rs587777247" 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=RCV000106405" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000106405" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000106405</a>
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<p>In a Japanese woman with hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>), <a href="#19" class="mim-tip-reference" title="Konno, T., Tada, M., Tada, M., Koyama, A., Nozaki, H., Harigaya, Y., Nishimiya, J., Matsunaga, A., Yoshikura, N., Ishihara, K., Arakawa, M., Isami, A., and 11 others. <strong>Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS.</strong> Neurology 82: 139-148, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24336230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24336230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24336230[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/10.1212/WNL.0000000000000046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24336230">Konno et al. (2014)</a> identified a heterozygous c.2342C-A transversion in the CSF1R gene, resulting in an ala781-to-glu (A781E) substitution at a highly conserved residue in the tyrosine kinase domain. The mutation was not found in the dbSNP database or in 124 controls. In vitro functional expression assays in HEK293 cells showed that the mutant protein did not undergo autophosphorylation, but coexpression of the mutant with wildtype did not suppress wildtype autophosphorylation, indicating that the mutation does not act in a dominant-negative manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24336230" 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 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</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">rs281860281 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281860281;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=rs281860281" 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=rs281860281" 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=RCV000031932 OR RCV001561353 OR RCV002482936" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000031932, RCV001561353, RCV002482936" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000031932...</a>
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<p>In affected members of a family (FTD368) with hereditary diffuse leukoencephalopathy with spheroids (HDLS; <a href="/entry/221820">221820</a>), originally reported by <a href="#17" class="mim-tip-reference" title="Knopman, D., Sung, J. H., Davis, D. <strong>Progressive familial leukodystrophy of late onset.</strong> Neurology 46: 429-434, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8614507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8614507</a>] [<a href="https://doi.org/10.1212/wnl.46.2.429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8614507">Knopman et al. (1996)</a>, <a href="#23" class="mim-tip-reference" title="Nicholson, A. M., Baker, M. C, Finch, N. A., Rutherford, N. J., Wider, C., Graff-Radford, N. R., Nelson, P. T., Clark, H. B., Wszolek, Z. K., Dickson, D. W., Knopman, D. S., Rademakers, R. <strong>CSF1R mutations link POLD and HDLS as a single disease entity.</strong> Neurology 80: 1033-1040, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23408870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23408870</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23408870[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/10.1212/WNL.0b013e31828726a7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23408870">Nicholson et al. (2013)</a> identified a heterozygous c.2345G-A transition in exon 18 of the CSF1R gene, resulting in an arg782-to-his (R782H) substitution in the kinase domain. The mutation segregated with the disorder in the family and was not found in 1,089 white, non-Hispanic control individuals. In vitro functional expression studies in HeLa cells showed that the R782H mutation abrogated CSF1R autophosphorylation, which would inhibit downstream signaling. Since the family had originally received a clinicopathologic diagnosis of pigmented orthochromatic leukodystrophy (POLD), the findings indicated that POLD and HDLS are a single disease entity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23408870+8614507" 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 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</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">rs1351319114 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1351319114;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=rs1351319114" 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=rs1351319114" 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=RCV000785984 OR RCV003727825" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000785984, RCV003727825" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000785984...</a>
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<p>In a 4-year-old Brazilian boy (family A), with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; <a href="/entry/618476">618476</a>), <a href="#13" class="mim-tip-reference" title="Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others. <strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong> Am. J. Hum. Genet. 104: 925-935, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982609</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982609[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982609">Guo et al. (2019)</a> identified compound heterozygous mutations in the CSF1R gene: a c.395C-T transition (c.395C-T, NM_005211), resulting in a pro132-to-leu (P132L) substitution, and a c.1441C-T transition, resulting in a gln481-to-ter (Q481X; <a href="#0011">164770.0011</a>) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The P132L variant was found once in the heterozygous state in the gnomAD database, and c.1441C-T was found in 1 control from 1,200 elderly healthy Brazilians. Analysis of patient cells indicated that the nonsense mutation resulted in nonsense-mediated mRNA decay. In vitro functional expression studies showed that cells carrying the P132L mutation had significantly decreased CSF1R-mediated phosphorylation of JNK (<a href="/entry/601158">601158</a>), consistent with a loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982609" 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>.0011 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</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"><span class="text-primary">●</span> rs917027829 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs917027829;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs917027829?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs917027829" 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=rs917027829" 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=RCV000624615 OR RCV000785985 OR RCV001849409 OR RCV001860422" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000624615, RCV000785985, RCV001849409, RCV001860422" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000624615...</a>
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<p>For discussion of the c.1441C-T transition (c.1441C-T, NM_005211) in the CSF1R gene, resulting in a gln481-to-ter (Q481X) substitution, that was found in compound heterozygous state in a patient with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; <a href="/entry/618476">618476</a>) by <a href="#13" class="mim-tip-reference" title="Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others. <strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong> Am. J. Hum. Genet. 104: 925-935, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982609</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982609[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982609">Guo et al. (2019)</a>, see <a href="#0010">164770.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982609" 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 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</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">rs1561912628 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1561912628;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=rs1561912628" 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=rs1561912628" 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=RCV000785986 OR RCV002469289" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000785986, RCV002469289" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000785986...</a>
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<p>In a 37-year-old Japanese woman (family B) with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; <a href="/entry/618476">618476</a>), <a href="#13" class="mim-tip-reference" title="Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others. <strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong> Am. J. Hum. Genet. 104: 925-935, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982609</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982609[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982609">Guo et al. (2019)</a> identified compound heterozygous mutations in the CSF1R gene: a G-to-A transition (c.1859-119G-A, NM_005211) in intron 13, resulting in aberrant splicing, and a 3-bp in-frame deletion (c.1879_1881del; <a href="#0013">164770.0013</a>), resulting in the deletion of lys627 in the intracellular kinase domain. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither variant was found in any available database, including gnomAD. Analysis of patient cells showed that the c.1859-119G-A variant resulted in a 117-bp insertion, leading to an elongated protein (Ser620delins40). In vitro functional expression studies showed that cells carrying both of these mutations significantly decreased CSF1R-mediated phosphorylation of JNK (<a href="/entry/601158">601158</a>), consistent with a loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982609" 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 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</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">rs1554101963 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554101963;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=rs1554101963" 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=rs1554101963" 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=RCV000522082 OR RCV000785987" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000522082, RCV000785987" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000522082...</a>
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<p>For discussion of the 3-bp in-frame deletion (c.1879_1881del, NM_005211) in the CSF1R gene, resulting in the deletion of lys627 in the intracellular kinase domain, that was found in compound heterozygous state in a patient with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; <a href="/entry/618476">618476</a>) by <a href="#13" class="mim-tip-reference" title="Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others. <strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong> Am. J. Hum. Genet. 104: 925-935, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982609</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982609[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982609">Guo et al. (2019)</a>, see <a href="#0012">164770.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982609" 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="0014" class="mim-anchor"></a>
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<strong>.0014 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</strong>
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CSF1R, 2-BP DEL, IVS14, 1969+115_1969+116
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1581289103 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1581289103;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=rs1581289103" 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=rs1581289103" 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=RCV000785988 OR RCV003329339" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000785988, RCV003329339" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000785988...</a>
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<p>In 2 sibs, born of consanguineous Chaldean parents (family C), with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; <a href="/entry/618476">618476</a>), <a href="#13" class="mim-tip-reference" title="Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others. <strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong> Am. J. Hum. Genet. 104: 925-935, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982609</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982609[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982609">Guo et al. (2019)</a> identified a homozygous 2-bp deletion deep within intron 14 of the CSF1R gene (c.1969+115_1969+116, NM_005211). The variant, which was found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. RT-PCR analysis of patients cells showed an abnormal transcript with a 99-bp insertion, resulting in premature termination (Pro658SerfsTer24). However, the mutation was subject to nonsense-mediated mRNA decay, suggesting a complete loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982609" 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>.0015 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</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">rs1561913526 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1561913526;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=rs1561913526" 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=rs1561913526" 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=RCV000785989" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000785989" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000785989</a>
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<p>In a male infant, born of consanguineous parents of Native Alaskan ancestry (family CSF1R_01), with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; <a href="/entry/618476">618476</a>), <a href="#24" class="mim-tip-reference" title="Oosterhof, N., Chang, I. J., Karimiani, E. G., Kuil, L. E., Jensen, D. M., Daza, R., Young, E., Astle, L., van der Linde, H. C., Shivaram, G. M., Demmers, J., Latimer, C. S., Keene, C. D., Loter, E., Maroofian, R., van Ham, T. J., Hevner, R. F., Bennett, J. T. <strong>Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia.</strong> Am. J. Hum. Genet. 104: 936-947, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982608[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982608">Oosterhof et al. (2019)</a> identified a homozygous G-to-C transversion (c.1754-1G-C, NM_005211.3) in intron 12 of the CSF1R gene. The mutation, which was found by exome sequencing, segregated with the disorder in the family. The variant was predicted to result in the skipping of exon 13 and produce an in-frame protein product change (Gly585_Lys619delinsAla) within the tyrosine kinase domain. The variant was not found in the ExAC or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed, but the variant was predicted to result in a loss of function. The patient died of bacteremia at 10 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982608" 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"><span class="text-primary">●</span> rs184499252 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs184499252;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs184499252?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs184499252" 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=rs184499252" 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=RCV000785990 OR RCV003117575" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000785990, RCV003117575" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000785990...</a>
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<p>In a 24-year-old man, born of consanguineous Arab parents (family CSF1R_02) with brain abnormalities and neurodegeneration (BANDDOS; <a href="/entry/618476">618476</a>), <a href="#24" class="mim-tip-reference" title="Oosterhof, N., Chang, I. J., Karimiani, E. G., Kuil, L. E., Jensen, D. M., Daza, R., Young, E., Astle, L., van der Linde, H. C., Shivaram, G. M., Demmers, J., Latimer, C. S., Keene, C. D., Loter, E., Maroofian, R., van Ham, T. J., Hevner, R. F., Bennett, J. T. <strong>Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia.</strong> Am. J. Hum. Genet. 104: 936-947, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982608[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.03.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30982608">Oosterhof et al. (2019)</a> identified a homozygous c.1929C-A transversion in intron 14 of the CSF1R gene, resulting in a his643-to-gln (H643Q) substitution in the kinase domain. The mutation, which was found by exome sequencing, segregated with the disorder in the family. It was not found in the ExAC or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed, but the variant was predicted to result in a loss of function, most likely with a hypomorphic effect. X-rays showed no evidence of osteopetrosis and there was no known history of hypocalcemia. A similarly affected brother had died at age 21 years, but DNA was not available for study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982608" 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 href="#Gisselbrecht1987" class="mim-tip-reference" title="Gisselbrecht, S., Fichelson, S., Sola, B., Bordereaux, D., Hampe, A., Andre, C., Galibert, F., Tambourin, P. E. <strong>Frequent c-fms activation by proviral insertion in mouse myeloblastic leukaemias.</strong> Nature 329: 259-261, 1987.">Gisselbrecht et al. (1987)</a>; <a href="#Hampe1984" class="mim-tip-reference" title="Hampe, A., Gobet, M., Sherr, C. J., Galibert, F. <strong>Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases.</strong> Proc. Nat. Acad. Sci. 81: 85-89, 1984.">Hampe et al. (1984)</a>; <a href="#Verbeek1985" class="mim-tip-reference" title="Verbeek, J. S., van Heerikhuizen, H., de Pauw, B. E., Haanen, C., Bloemers, H. P. J., Van de Ven, W. J. M. <strong>A hereditary abnormal c-fms proto-oncogene in a patient with acute lymphocytic leukaemia and congenital hypothyroidism.</strong> Brit. J. Haemat. 61: 135-138, 1985.">Verbeek et al.
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(1985)</a>; <a href="#Verbeek1985" class="mim-tip-reference" title="Verbeek, J. S., van Heerikhuizen, H., de Pauw, B. E., Haanen, C., Bloemers, H. P. J., Van de Ven, W. J. M. <strong>A hereditary abnormal c-fms proto-oncogene in a patient with acute lymphocytic leukaemia and congenital hypothyroidism.</strong> Brit. J. Haemat. 61: 135-138, 1985.">Verbeek et al. (1985)</a>; <a href="#Xu1985" class="mim-tip-reference" title="Xu, D. Q., Guilhot, S., Galibert, F. <strong>Restriction fragment length polymorphism of the human c-fms gene.</strong> Proc. Nat. Acad. Sci. 82: 2862-2865, 1985.">Xu et al. (1985)</a>; <a href="#Yarden1988" class="mim-tip-reference" title="Yarden, Y., Ullrich, A. <strong>Growth factor receptor tyrosine kinases.</strong> Ann. Rev. Biochem. 57: 443-478, 1988.">Yarden and Ullrich
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Aikawa, Y., Katsumoto, T., Zhang, P., Shima, H., Shino, M., Terui, K., Ito, E., Ohno, H., Stanley, E. R., Singh, H., Tenen, D. G., Kitabayashi, I.
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<strong>PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. (Letter)</strong>
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Nature Med. 16: 580-585, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20418886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20418886</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20418886[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20418886" 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/nm.2122" target="_blank">Full Text</a>]
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Baba, Y., Ghetti, B., Baker, M. C., Uitti, R. J., Hutton, M. L., Yamaguchi, K., Bird, T., Lin, W., DeLucia, M. W., Dickson, D. W., Wszolek, Z. K.
|
|
<strong>Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred.</strong>
|
|
Acta Neuropath. 111: 300-311, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16523341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16523341</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16523341" 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/10.1007/s00401-006-0046-z" target="_blank">Full Text</a>]
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Benz-Lemoine, E., Brizard, A., Huret, J.-L., Babin, P., Guilhot, F., Couet, D., Tanzer, J.
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<strong>Malignant histiocytosis: a specific t(2;5)(p23;q35) translocation? Review of the literature.</strong>
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Blood 72: 1045-1047, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3416066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3416066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3416066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Boultwood, J., Rack, K., Kelly, S., Madden, J., Sakaguchi, A. Y., Wang, L.-M., Oscier, D. G., Buckle, V. J., Wainscoat, J. S.
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<strong>Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion.</strong>
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Proc. Nat. Acad. Sci. 88: 6176-6180, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1829836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1829836</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1829836" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Dai, X.-M., Zong, X.-H., Akhter, M. P., Stanley, E. R.
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<strong>Osteoclast deficiency results in disorganized matrix, reduced mineralization, and abnormal osteoblast behavior in developing bone.</strong>
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J. Bone Miner. Res. 19: 1441-1451, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15312244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15312244</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15312244" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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<a id="Eccles1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eccles, M. R.
|
|
<strong>Genes encoding the platelet-derived growth factor (PDGF) receptor and colony-stimulating factor 1 (CSF-1) receptor are physically associated in mice as in humans.</strong>
|
|
Gene 108: 285-288, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1660841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1660841</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1660841" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0378-1119(91)90447-j" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Erblich2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., Pollard, J. W.
|
|
<strong>Absence of colony-stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits.</strong>
|
|
PLoS One 6: e26317, 2011. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22046273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22046273</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22046273[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22046273" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1371/journal.pone.0026317" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Faccio2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Faccio, R., Takeshita, S., Zallone, A., Ross, F. P., Teitelbaum, S. L.
|
|
<strong>c-Fms and the alpha-V-beta-3 integrin collaborate during osteoclast differentiation.</strong>
|
|
J. Clin. Invest. 111: 749-758, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12618529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12618529</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12618529[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12618529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI16924" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Ginhoux2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., Samokhvalov, I. M., Merad, M.
|
|
<strong>Fate mapping analysis reveals that adult microglia derive from primitive macrophages.</strong>
|
|
Science 330: 841-845, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20966214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20966214</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20966214[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20966214" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1194637" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Gisselbrecht1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gisselbrecht, S., Fichelson, S., Sola, B., Bordereaux, D., Hampe, A., Andre, C., Galibert, F., Tambourin, P. E.
|
|
<strong>Frequent c-fms activation by proviral insertion in mouse myeloblastic leukaemias.</strong>
|
|
Nature 329: 259-261, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3476856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3476856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3476856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/329259a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Groffen1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Groffen, J., Heisterkamp, N., Spurr, N. K., Dana, S. L., Wasmuth, J. J., Stephenson, J. R.
|
|
<strong>Regional assignment of the human c-fms oncogene to band q34 of chromosome 5. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 484 only, 1984.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Gross2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 1/8/2013.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Guo2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others.
|
|
<strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong>
|
|
Am. J. Hum. Genet. 104: 925-935, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982609</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982609[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2019.03.004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Hampe1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hampe, A., Gobet, M., Sherr, C. J., Galibert, F.
|
|
<strong>Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 85-89, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6582485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6582485</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6582485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.81.1.85" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Hampe1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hampe, A., Shamoon, B.-M., Gobet, M., Sherr, C. J., Galibert, F.
|
|
<strong>Nucleotide sequence and structural organization of the human FMS proto-oncogene.</strong>
|
|
Oncogene Res. 4: 9-17, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2524025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2524025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2524025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="How1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
How, G.-F., Venkatesh, B., Brenner, S.
|
|
<strong>Conserved linkage between the puffer fish (Fugu rubripes) and human genes for platelet-derived growth factor receptor and macrophage colony-stimulating factor receptor.</strong>
|
|
Genome Res. 6: 1185-1191, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8973913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8973913</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8973913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gr.6.12.1185" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Knopman1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Knopman, D., Sung, J. H., Davis, D.
|
|
<strong>Progressive familial leukodystrophy of late onset.</strong>
|
|
Neurology 46: 429-434, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8614507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8614507</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8614507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.46.2.429" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Kondo2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kondo, M., Scherer, D. C., Miyamoto, T., King, A. G., Akashi, K., Sugamura, K., Weissman, I. L.
|
|
<strong>Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines.</strong>
|
|
Nature 407: 383-386, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11014194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11014194</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11014194" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/35030112" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Konno2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Konno, T., Tada, M., Tada, M., Koyama, A., Nozaki, H., Harigaya, Y., Nishimiya, J., Matsunaga, A., Yoshikura, N., Ishihara, K., Arakawa, M., Isami, A., and 11 others.
|
|
<strong>Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS.</strong>
|
|
Neurology 82: 139-148, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24336230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24336230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24336230[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24336230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/WNL.0000000000000046" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Lamprecht2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lamprecht, B., Walter, K., Kreher, S., Kumar, R., Hummel, M., Lenze, D., Kochert, K., Bouhlel, M. A., Richter, J., Soler, E., Stadhouders, R., Johrens, K., and 13 others.
|
|
<strong>Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma.</strong>
|
|
Nature Med. 16: 571-579, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20436485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20436485</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20436485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nm.2129" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Le Beau1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Le Beau, M. M., Westbrook, C. A., Diaz, M. O., Larson, R. A., Rowley, J. D., Gasson, J. C., Golde, D. W., Sherr, C. J.
|
|
<strong>Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders.</strong>
|
|
Science 231: 984-987, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3484837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3484837</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3484837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.3484837" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Morgan1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morgan, R., Hecht, B. K., Sandberg, A. A., Hecht, F., Smith, S. D.
|
|
<strong>Chromosome 5q35 breakpoint in malignant histiocytosis. (Letter)</strong>
|
|
New Eng. J. Med. 314: 1322 only, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3702936/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3702936</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3702936" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/nejm198605153142016" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Nicholson2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nicholson, A. M., Baker, M. C, Finch, N. A., Rutherford, N. J., Wider, C., Graff-Radford, N. R., Nelson, P. T., Clark, H. B., Wszolek, Z. K., Dickson, D. W., Knopman, D. S., Rademakers, R.
|
|
<strong>CSF1R mutations link POLD and HDLS as a single disease entity.</strong>
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Neurology 80: 1033-1040, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23408870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23408870</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23408870[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23408870" 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.0b013e31828726a7" target="_blank">Full Text</a>]
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<a id="Oosterhof2019" class="mim-anchor"></a>
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Oosterhof, N., Chang, I. J., Karimiani, E. G., Kuil, L. E., Jensen, D. M., Daza, R., Young, E., Astle, L., van der Linde, H. C., Shivaram, G. M., Demmers, J., Latimer, C. S., Keene, C. D., Loter, E., Maroofian, R., van Ham, T. J., Hevner, R. F., Bennett, J. T.
|
|
<strong>Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia.</strong>
|
|
Am. J. Hum. Genet. 104: 936-947, 2019.
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30982608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30982608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30982608[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30982608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2019.03.010" target="_blank">Full Text</a>]
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<a id="Rademakers2012" class="mim-anchor"></a>
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Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M., Adamson, J., Kouri, N., and 26 others.
|
|
<strong>Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.</strong>
|
|
Nature Genet. 44: 200-205, 2012.
|
|
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22197934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22197934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22197934[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22197934" 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/ng.1027" target="_blank">Full Text</a>]
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|
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|
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|
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<a id="26" class="mim-anchor"></a>
|
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<a id="Ridge1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ridge, S. A., Worwood, M., Oscier, D., Jacobs, A., Padua, R. A.
|
|
<strong>FMS mutations in myelodysplastic, leukemic, and normal subjects.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 1377-1380, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2406720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2406720</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2406720" 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/10.1073/pnas.87.4.1377" target="_blank">Full Text</a>]
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|
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|
|
|
|
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|
|
<a id="27" class="mim-anchor"></a>
|
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<a id="Roberts1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roberts, W. M., Look, A. T., Roussel, M. F., Sherr, C. J.
|
|
<strong>Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes.</strong>
|
|
Cell 55: 655-661, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2846185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2846185</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2846185" 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/10.1016/0092-8674(88)90224-3" target="_blank">Full Text</a>]
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|
|
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|
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|
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<li>
|
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<a id="28" class="mim-anchor"></a>
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<a id="Sapi1994" class="mim-anchor"></a>
|
|
<div class="">
|
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<p class="mim-text-font">
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Sapi, E., Flick, M. B., Kacinski, B. M.
|
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<strong>The first intron of human c-fms proto-oncogene contains a processed pseudogene (RPL7P) for ribosomal protein L7.</strong>
|
|
Genomics 22: 641-645, 1994.
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001978" 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/10.1006/geno.1994.1440" target="_blank">Full Text</a>]
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|
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|
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<a id="Swerdlow2009" class="mim-anchor"></a>
|
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|
|
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|
|
Swerdlow, R. H., Miller, B. B., Lopes, M. B. S., Mandell, J. W., Wooten, G. F., Damgaard, P., Manning, C., Fowler, M., Brashear, H. R.
|
|
<strong>Autosomal dominant subcortical gliosis presenting as frontotemporal dementia.</strong>
|
|
Neurology 72: 260-267, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19153373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19153373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19153373" 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.0000339484.61490.a4" target="_blank">Full Text</a>]
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<a id="Van Cong1989" class="mim-anchor"></a>
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Van Cong, N., Fichelson, S., Gross, M. S., Sola, B., Bordereaux, D., de Tand, M. F., Guilhot, S., Gisselbrecht, S., Frezal, J., Tambourin, P.
|
|
<strong>The human homologues of Fim1, Fim2/c-Fms, and Fim3, three retroviral integration regions involved in mouse myeloblastic leukemias, are respectively located on chromosomes 6p23, 5q33, and 3q27.</strong>
|
|
Hum. Genet. 81: 257-263, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2921036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2921036</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2921036" 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/10.1007/BF00279000" target="_blank">Full Text</a>]
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<a id="31" class="mim-anchor"></a>
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<a id="Van Cong1987" class="mim-anchor"></a>
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Van Cong, N., Fichelson, S., Sola, B., Gross, M. S., Jegou-Foubert, C., Bordereaux, D., Gisselbrecht, S., Tambourin, P. E., Frezal, J.
|
|
<strong>Assignment of Fim-2 (CSF1R) to chromosome 5q33 (in situ hybridization) and Fim-3 to chromosome 3 (somatic cell analysis) region 3q27 (in situ hybridization). (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 670 only, 1987.
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|
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<a id="Verbeek1985" class="mim-anchor"></a>
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Verbeek, J. S., Roebroek, A. J. M., van den Ouweland, A. M. W., Bloemers, H. P. J., Van de Ven, W. J. M.
|
|
<strong>Human c-fms proto-oncogene: comparative analysis with an abnormal allele.</strong>
|
|
Molec. Cell. Biol. 5: 422-426, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3974576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3974576</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3974576" 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/10.1128/mcb.5.2.422-426.1985" target="_blank">Full Text</a>]
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Verbeek, J. S., van Heerikhuizen, H., de Pauw, B. E., Haanen, C., Bloemers, H. P. J., Van de Ven, W. J. M.
|
|
<strong>A hereditary abnormal c-fms proto-oncogene in a patient with acute lymphocytic leukaemia and congenital hypothyroidism.</strong>
|
|
Brit. J. Haemat. 61: 135-138, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3863666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3863666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3863666" 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/10.1111/j.1365-2141.1985.tb04068.x" target="_blank">Full Text</a>]
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Xu, D. Q., Guilhot, S., Galibert, F.
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<strong>Restriction fragment length polymorphism of the human c-fms gene.</strong>
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Proc. Nat. Acad. Sci. 82: 2862-2865, 1985.
|
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|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2986142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2986142</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2986142" 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/10.1073/pnas.82.9.2862" target="_blank">Full Text</a>]
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<a id="Yarden1988" class="mim-anchor"></a>
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Yarden, Y., Ullrich, A.
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<strong>Growth factor receptor tyrosine kinases.</strong>
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Ann. Rev. Biochem. 57: 443-478, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3052279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3052279</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3052279" 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/10.1146/annurev.bi.57.070188.002303" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 06/19/2019
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Cassandra L. Kniffin - updated : 11/3/2014<br>Cassandra L. Kniffin - updated : 3/5/2014<br>Matthew B. Gross - updated : 1/8/2013<br>Matthew B. Gross - updated : 3/14/2012<br>Cassandra L. Kniffin - updated : 2/6/2012<br>Ada Hamosh - updated : 12/28/2010<br>Cassandra L. Kniffin - updated : 5/27/2010<br>Marla J. F. O'Neill - updated : 2/17/2005<br>Ada Hamosh - updated : 9/20/2000<br>Victor A. McKusick - updated : 3/4/1997
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Victor A. McKusick : 6/2/1986
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carol : 02/18/2025
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alopez : 06/21/2019<br>ckniffin : 06/19/2019<br>carol : 08/21/2018<br>carol : 08/20/2018<br>carol : 08/17/2018<br>carol : 11/13/2014<br>mcolton : 11/4/2014<br>ckniffin : 11/3/2014<br>alopez : 3/27/2014<br>ckniffin : 3/5/2014<br>carol : 1/8/2013<br>mgross : 1/8/2013<br>carol : 11/6/2012<br>mgross : 3/14/2012<br>carol : 2/7/2012<br>ckniffin : 2/6/2012<br>alopez : 1/3/2011<br>terry : 12/28/2010<br>wwang : 6/15/2010<br>ckniffin : 5/27/2010<br>wwang : 3/7/2005<br>terry : 2/17/2005<br>alopez : 9/20/2000<br>psherman : 9/10/1999<br>psherman : 11/23/1998<br>psherman : 11/21/1998<br>carol : 7/8/1998<br>dkim : 6/30/1998<br>jamie : 3/4/1997<br>jenny : 3/4/1997<br>jenny : 3/4/1997<br>terry : 2/24/1997<br>carol : 9/13/1994<br>carol : 1/8/1993<br>carol : 1/6/1993<br>supermim : 3/16/1992<br>carol : 2/16/1992<br>carol : 12/4/1991
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<span class="mim-font">
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<strong>*</strong> 164770
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<h3>
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COLONY-STIMULATING FACTOR 1 RECEPTOR; CSF1R
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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MCSFR<br />
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ONCOGENE FMS; FMS<br />
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c-FMS<br />
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CD115 ANTIGEN; CD115<br />
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V-FMS MCDONOUGH FELINE SARCOMA VIRAL ONCOGENE HOMOLOG, FORMERLY
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: CSF1R</em></strong>
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<strong>SNOMEDCT:</strong> 702427005;
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<strong>ICD10CM:</strong> G93.44;
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Cytogenetic location: 5q32
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Genomic coordinates <span class="small">(GRCh38)</span> : 5:150,053,295-150,113,365 </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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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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5q32
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<span class="mim-font">
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Brain abnormalities, neurodegeneration, and dysosteosclerosis
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<span class="mim-font">
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618476
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Autosomal recessive
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<span class="mim-font">
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3
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<span class="mim-font">
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Leukoencephalopathy, diffuse hereditary, with spheroids 1
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<span class="mim-font">
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221820
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The CSF1R gene, also known as c-FMS, encodes a tyrosine kinase growth factor receptor for colony-stimulating factor-1 (CSF1; 120420), the macrophage- and monocyte-specific growth factor (Ridge et al., 1990). </p><p>The CSF1R gene is expressed in mononuclear phagocytes in the brain, known as microglia, which play a role in neuronal and brain development (summary by Erblich et al., 2011), as well as in osteoclasts, which play an important role in bone mineralization (summary by Dai et al., 2004). Phosphorylation of CSF1R triggered by ligand binding to the receptor activates multiple downstream kinase pathways, including PI3K (see 171834), ERK1/2 (see 176948), and JNK (see 601158) (summary by Guo et al., 2019). </p>
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<strong>Cloning and Expression</strong>
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<p>How et al. (1996) determined the sequences of the homologs of the human PDGFRB and CSF1R genes in the pufferfish (Fugu rubripes). Amino acid sequences of the Fugu and human PGFRB and CSF1R genes showed an overall homology of 45% and 39%, respectively. </p><p>In postnatal mouse brain, Erblich et al. (2011) found that Csf1r is expressed in microglia, but not in neurons, astrocytes, or glial cells. </p>
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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 class="mim-text-font">
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<p>Hampe et al. (1989) demonstrated that the FMS gene contains 21 small exons interrupted by introns ranging in size from 6.3 kb to less than 0.1 kb. </p><p>Roberts et al. (1988) demonstrated that a 5-prime untranslated exon of CSF1R is separated by a 26-kb intron from the 32-kb receptor coding sequences. Furthermore, the 3-prime end of the PDGFRB gene is located less than 0.5 kb upstream from this exon. The authors stated that the as yet unidentified CSF1R promoter/enhancer sequences may be confined to the nucleotides separating the 2 genes or could potentially lie within the PDGFR gene itself. Similarities in chromosomal localization, organization, and encoded amino acid sequences suggested that the CSF1R and PDGFR genes arose through duplication. The human homolog of the murine Fim2 proviral integration region corresponds to the 5-prime end of the FMS gene. </p><p><strong><em>Pseudogene</em></strong></p><p>
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During sequence analysis of the first intron of the human FMS gene, Sapi et al. (1994) identified an open reading frame encoding the ribosomal protein L7 (RPL7; 604166). The sequence was identical to the full-length RPL7 cDNA sequence but lacked any recognizable introns, had a 30-bp poly(A) tail, and was bracketed by 2 perfect direct repeats of 14 bp. Sapi et al. (1994) demonstrated that despite the fact that the 5-prime flanking region of the RPL7 sequence contained a potential TATA box upstream of an intact open reading frame, the pseudogene (RPL7P) was not actively transcribed. </p>
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<h4>
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<span class="mim-font">
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<strong>Mapping</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>The FMS oncogene was assigned to chromosome 5 by study of mouse-man somatic cell hybrids. The location was narrowed to 5q34 by the study of hamster-human cell hybrids with well-defined deletions of 5q (Groffen et al., 1984). The order on the long arm was found to be centromere--leuS--HEXB--EMTB--FMS--CHR. By in situ hybridization, Le Beau et al. (1986) assigned the FMS gene to chromosome 5q33.2 or 5q33.3 and the GMCSF (138960) gene to chromosome 5q23-q31. </p><p>Roberts et al. (1988) demonstrated that the CSF1R gene and the PDGFR1 (173410) gene are physically associated in a head-to-tail array, with less than 500 bp between the polyadenylation signal of the PDGFRB gene and the transcription start point of the CSF1R gene. By pulsed field gel electrophoresis, Eccles (1991) demonstrated that the same is true in the mouse where a 425-kb fragment hybridizes with the 3-prime end of PDGFR1 and the 5-prime end of CSF1R. In Fugu (pufferfish), How et al. (1996) demonstrated that the 2 genes are closely linked in a head-to-tail array with 2.2 kb of intergenic sequence. </p><p>Three mouse genomic domains, Fim1, Fim2, and Fim3, have been described as proviral integration regions frequently involved in the early stages of myeloblastic leukemogenesis induced in vivo or in vitro by the Friend murine leukemia virus. Fim2 has been identified as the 5-prime end of the Fms protooncogene. Van Cong et al. (1987, 1989) confirmed the localization of human FIM2/FMS on chromosome 5q33. By Southern blot analysis of DNA from human/rodent hybrids and by in situ hybridization, they mapped FIM1 to human chromosome 6p23-p22.3 and FIM3 to human chromosome 3q27. </p><p>Gross (2013) mapped the CSF1R gene to chromosome 5q32 based on an alignment of the CSF1R sequence (GenBank BC047521) with the genomic sequence (GRCh37).</p>
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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 class="mim-text-font">
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<p>Kondo et al. (2000) showed that a clonogenic common lymphoid progenitor, a bone marrow-resident cell that gives rise exclusively to lymphocytes (T, B, and natural killer cells), can be redirected to the myeloid lineage by stimulation through exogenously expressed interleukin-2 receptor (146710) and GMCSF receptor (138981, 306250). Analysis of mutants of the beta-chain of the IL2 receptor revealed that the granulocyte and monocyte differentiation signals are triggered by different cytoplasmic domains, showing that the signaling pathways responsible for these unique developmental outcomes are separable. Finally, Kondo et al. (2000) showed that the endogenous myelomonocytic cytokine receptors for GM-CSF and macrophage colony-stimulating factor (CSF1R) are expressed at low to moderate levels on the more primitive hematopoietic stem cells, are absent on common lymphoid progenitors, and are upregulated after myeloid lineage induction by IL2 (147680). Kondo et al. (2000) concluded that cytokine signaling can regulate cell fate decisions and proposed that a critical step in lymphoid commitment is downregulation of cytokine receptors that drive myeloid cell development. </p><p>Faccio et al. (2003) retrovirally transduced beta-3 integrin (ITGB3; 173470) -/- osteoclast precursors with chimeric CSF1R constructs containing various cytoplasmic domain mutations and found that CSF1R tyr697 was required for normalization of osteoclastogenesis and ERK activation (see 176948). Overexpression of FOS (164810) normalized the number of ITGB3 -/- osteoclasts in vitro but not their ability to resorb dentin. Faccio et al. (2003) concluded that whereas CSF1R and alpha-V-beta-3 integrin collaborate in the osteoclastogenic process through shared activation of the ERK/FOS signaling pathway, the integrin is essential for matrix degradation. </p><p>Using fate mapping analysis, Ginhoux et al. (2010) showed that adult microglia derive from primitive macrophages. They showed that microglia develop in mice that lack colony-stimulating factor-1 (CSF1; 120420) but are absent in Csf1 receptor-deficient mice. In vivo lineage tracing studies established that adult microglia derive from primitive myeloid progenitors expressing Runx1 (151385) that arise before embryonic day 8. Ginhoux et al. (2010) concluded that their results identified microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders. </p>
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<h4>
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<span class="mim-font">
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<strong>Cytogenetics</strong>
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<span class="mim-text-font">
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<p>Le Beau et al. (1986) found that the FMS and GM-CSF genes were both deleted from chromosome 5q- in bone marrow cells of 2 patients with refractory anemia and del(5)(q15-q33.3) (see chromosome 5q deletion syndrome; 153550). </p><p>Morgan et al. (1986) pointed out that a break at 5q35 has been found in several cases of malignant histiocytosis, a neoplastic process characterized by fever, progressive wasting, lymphadenopathy, hepatosplenomegaly, and the proliferation of atypical histiocytes at all stages of maturation with frequent phagocytic activity. They suggested that at the molecular level the change in band 5q35 may affect the FMS oncogene responsible for the receptor for mononuclear-phagocyte growth factor and thereby have a role in causing malignant histiocytosis. Benz-Lemoine et al. (1988) also suggested that a breakpoint in 5q35 may be critical to the development of malignant histiocytosis. </p><p>Boultwood et al. (1991) found loss of both CSF1R alleles in 10 patients with myelodysplasia and a 5q deletion; 6 were hemizygous and 4 were homozygous for CSF1R loss. Boultwood et al. (1991) suggested that loss of this hemopoietic growth factor receptor gene may also be important in the pathogenesis of myeloid leukemia. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p><strong><em>Somatic Mutations</em></strong></p><p>
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Among 110 patients with myelodysplastic and leukemic disorders, Ridge et al. (1990) found somatic mutations in codon 969 of the CSF1R gene in 14 (12.7%) and in codon 301 in 2 (1.8%). The tyrosine residue at codon 969 was shown to be involved in a negative regulatory activity, which is disrupted by amino acid substitutions. Mutations at codon 301 lead to neoplastic transformation by ligand independence and constitutive tyrosine kinase activity of the receptor. Somatic mutations were most prevalent in chronic myelomonocytic leukemia (20%) and type M4 acute myeloblastic leukemia (23%), both of which are characterized by monocytic differentiation. One of 50 hematologically normal individuals had a 969C-T transition as a constitutional change, which may represent a predisposition to these particular malignancies. </p><p>Lamprecht et al. (2010) found that Reed-Sternberg cells in Hodgkin lymphoma (236000) demonstrated upregulation of CSF1R and CSF1 mRNA and constitutive activation of CSF1R, which correlated with increased proliferation of the Reed-Sternberg cells. Non-Hodgkin cell lines did not express either gene, suggesting that the expression in Reed-Sternberg cells was aberrant. Analysis of CSF1R transcripts in Reed-Sternberg cells showed use of an alternative transcription start site located about 6.2-kb upstream of the normal myeloid transcription start site: this sequence corresponded to a long terminal repeat (LTR) of the mammalian apparent LTR retrotransposon (MALR) THE1B family. LTRs derived from ancient retroviral infections have accumulated in the mammalian genome, and mammalian organisms have devised a number of surveillance mechanisms to silence these elements early in development, usually by DNA methylation. The LTR region was found to contain a number of putative binding sites for transcription factors (i.e., NFKB; 164011) that were expressed in the Reed-Sternberg cells. Further studies indicated that the LTR is normally repressed by epigenetic methylation, and that Reed-Sternberg cells had lost this methylation. In addition, nearly all Reed-Sternberg cells studied had lost expression of the transcriptional repressor CBFA2T3 (603870). LTR-driven CSF1R transcripts were also found in anaplastic large cell lymphoma. Lamprecht et al. (2010) suggested that inhibition of CSF1R signaling may be of therapeutic value in Hodgkin lymphoma. </p><p><strong><em>Hereditary Diffuse Leukoencephalopathy With Spheroids</em></strong></p><p>
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By linkage analysis followed by whole-exome sequencing of the family with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820) reported by Swerdlow et al. (2009), Rademakers et al. (2012) identified a heterozygous mutation in the CSF1R gene (164770.0001). Sequencing of this gene in 13 additional probands with HDLS identified a different heterozygous mutation in each (see, e.g., 164770.0002-164770.0005). The mutations cosegregated with the disorder in all families for which DNA from multiple affected individuals was available, including the family reported by Baba et al. (2006). The phenotype was characterized by adult-onset of a rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often died of dementia within 6 years of onset. Brain imaging showed patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes. In vitro functional expression studies of some of the missense mutations indicated that the mutant proteins did not show autophosphorylation, suggesting a defect in kinase activity that likely also affects downstream targets. The mutant proteins probably also act in a dominant-negative manner, since CSF1R assembles into homodimers. Overall, the findings indicated that a defect in microglial signaling and function resulting from CSF1R mutations can cause central nervous system degeneration. </p><p>In 7 Japanese probands with HDLS, Konno et al. (2014) identified 6 different heterozygous mutations in the CSF1R gene (see, e.g., 164770.0004; 164770.0006-164770.0008). Two of the mutations resulted in truncated proteins, indicating that haploinsufficiency is sufficient to cause the disorder. In vitro functional expression studies in HEK293 cells showed that none of the mutant CSF1R proteins, including those caused by missense mutations, were able to autophosphorylate. However, coexpression of the mutants with wildtype did not suppress wildtype autophosphorylation, indicating that the mutations do not act in a dominant-negative manner. </p><p><strong><em>Brain Abnormalities, Neurodegeneration, and Dysosteosclerosis</em></strong></p><p>
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In 6 patients from 3 unrelated families with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; 618476), Guo et al. (2019) identified homozygous or compound heterozygous mutations in the CSF1R gene (164770.0010-164770.0014). The mutations, which were found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Five different mutations were identified, including a nonsense and a missense variant in compound heterozygosity (see 164770.0010), an in-frame deletion and a deep intronic mutation in compound heterozygosity (see 164770.0012), and a deep intronic mutation in homozygosity (164770.0014). In vitro functional expression studies of 3 of the variants showed that they were associated with decreased JNK (MAPK8; 601158) phosphorylation, consistent with impaired function. The authors noted that the skeletal phenotype in these patients was not as severe as that observed in Csf1r-null mice, suggesting that some of the mutations likely result in hypomorphic alleles. However, the overall findings suggested that biallelic mutations that result in decreased CSF1R produce the skeletal phenotype, as heterozygous mutations that cause HDLS do not result in skeletal abnormalities. Moreover, Guo et al. (2019) noted that the heterozygous parental carriers in their study did not have manifestations, suggesting that HDLS mutations likely act via a dominant-negative effect. </p><p>In 2 unrelated patients with variable manifestations of BANDDOS, Oosterhof et al. (2019) identified homozygous mutations in the CSF1R gene (164770.0015 and 164770.0016). Functional studies of the variants and studies of patient cells were not performed, but 1 was a splice site mutation (164770.0015), predicted to result in a loss of function, and the other was a missense mutation (164770.0016), predicted to have a hypomorphic effect. The patient with the missense mutation did not have apparent skeletal involvement. </p>
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<span class="mim-font">
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<strong>Animal Model</strong>
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<span class="mim-text-font">
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<p>Dai et al. (2004) found that Csf1r-null mice had frequent spontaneous fractures and decreased bone strength associated with an expanded epiphyseal chondrocyte region, poorly formed cortex with disorganized collagen fibrils, and a severely disturbed matrix structure. Since Csf1r is expressed in osteoclasts, the findings suggesting that mutant mice had a deficiency of osteoclast-mediated regulation of osteoblasts during formation of lamellar bone. </p><p>Aikawa et al. (2010) found that mouse MOZ/TIF2 (see 601408)-induced AML stem cells with high expression of Csf1r had increased leukemia initiating activity than AML stem cells with same amount of MOZ/TIF2 protein and low expression of Csf1r, when transplanted in irradiated mice. The high Csf1r expressing cells had the phenotype of granulocyte-macrophage progenitors and differentiated monocytes. In mice with leukemia due to these cells, treatment with a drug-inducible suicide gene targeting Csf1r-expressing cells resulted in curing of the leukemia for up to 6 months compared to controls. Induction of AML was suppressed in Csf1r-deficient mice, and Csf1r inhibitors slowed the progression of MOZ/TIF2-induced AML. Increased Csf1r expression was due mainly to the hematopoietic transcription factor PU.1 (165170), which was required for the initiation and maintenance of MOZ/TIF2-induced AML by increasing transcription of Csf1r. Aikawa et al. (2010) suggested that CSF1R is crucial for leukemia induced by MOZ fusion and indicated that targeting of PU.1 may be a therapeutic option. </p><p>Erblich et al. (2011) found that Csf1r-null mice had postnatal developmental brain abnormalities, including enlarged ventricles, periventricular changes, parenchymal volume loss, thinning of the cerebral cortex, and propensity to hydrocephalus. These changes were associated with severely decreased numbers of microglia in the brain. Mutant mice also died early. </p><p>Oosterhof et al. (2019) found that knockdown of the csf1r homologs in zebrafish resulted in lack of microglia in the brain. Vertebral arches in mutant animals were smaller compared to controls, which the authors suggested may recapitulate osteopetrosis. These abnormalities were associated with downregulation of cux1 (116896), a transcription factor present in neurons. </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>16 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 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</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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CSF1R, MET875THR
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<br />
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SNP: rs281860279,
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ClinVar: RCV000022684, RCV005089298
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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 large family with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820) originally reported by Swerdlow et al. (2009), Rademakers et al. (2012) identified a heterozygous 2624T-C transition in exon 20 of the CSF1R gene, resulting in a met875-to-thr (M875T) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. In vitro functional expression studies indicated that the mutant protein did not show autophosphorylation, suggesting a defect in kinase activity that likely also affects downstream targets. The mutant protein probably also acts in a dominant-negative manner, since CSF1R assembles into homodimers. </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">
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<strong>.0002 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</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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CSF1R, GLU633LYS
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<br />
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SNP: rs281860269,
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ClinVar: RCV000022685, RCV001565941
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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 large family with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820), originally reported by Baba et al. (2006), Rademakers et al. (2012) identified a heterozygous 1897G-A transition in exon 14 of the CSF1R gene, resulting in a glu633-to-lys (E633K) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. In vitro functional expression studies indicated that the mutant protein did not show autophosphorylation, suggesting a defect in kinase activity that likely also affects downstream targets. The mutant protein probably also acts in a dominant-negative manner, since CSF1R assembles into homodimers. </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">
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<strong>.0003 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</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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CSF1R, IVS12AS, A-G, -2
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<br />
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SNP: rs281860267,
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ClinVar: RCV000022686
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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 pair of Norwegian monozygotic twins with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820), Rademakers et al. (2012) identified a heterozygous de novo A-to-G transition in intron 12 of the CSF1R gene (1754-2A-G), resulting in the skipping of exon 13, the in-frame loss of 34 consecutive amino acids, and the insertion of an alanine residue. The mutation was predicted to result in the loss of multiple amino acids in the intracellular tyrosine kinase domain. </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">
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<strong>.0004 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</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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CSF1R, ILE794THR
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<br />
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SNP: rs281860274,
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gnomAD: rs281860274,
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ClinVar: RCV000022687, RCV001090375, RCV003944835, RCV004795936
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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 hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820), Rademakers et al. (2012) identified a heterozygous 2381T-C transition in exon 18 of the CSF1R gene, resulting in an ile794-to-thr (I794T) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. </p><p>Konno et al. (2014) identified a heterozygous I794T substitution in 2 unrelated Japanese patients with HDLS. One had a family history of the disorder. In vitro functional expression assays in HEK293 cells showed that the mutant protein did not undergo autophosphorylation, but coexpression of the mutant with wildtype did not suppress wildtype autophosphorylation, indicating that the mutation does not act in a dominant-negative manner. </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>
|
|
<span class="mim-font">
|
|
<strong>.0005 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
|
|
</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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CSF1R, ASP837TYR
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<br />
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|
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SNP: rs387906662,
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|
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ClinVar: RCV000022688
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|
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</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman with sporadic occurrence of hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820), Rademakers et al. (2012) identified a heterozygous 2509G-T transversion in exon 19 of the CSF1R gene, resulting in an asp837-to-tyr (D837Y) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. The patient was diagnosed clinically with a disorder resembling corticobasal syndrome, and was identified from a cohort of 93 patients with various neurologic symptoms. At age 43 years, she developed a gradual decline in expressing herself, word-finding, and performing motor tasks with her right hand and leg. About 2 years later, she had executive dysfunction, bradykinesia, hyperreflexia, apraxia, rigidity in the upper limbs, and spasticity in the lower limbs. There was rapid neurologic deterioration, and she died at age 50. Brain MRI showed localized white matter hyperintensities in the frontal and parietal white matter on T2-weighted images. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
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|
|
CSF1R, 1-BP INS, 2060T
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|
|
<br />
|
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|
|
SNP: rs587777245,
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|
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|
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|
|
|
ClinVar: RCV000106403
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese woman with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820), Konno et al. (2014) identified a heterozygous 1-bp insertion (c.2060insT) in the CSF1R gene, resulting in a frameshift and premature termination (Ser688GlufsTer13). The mutation was not found in the dbSNP database or in 124 healthy controls. She had onset of the disorder at age 41 years and died at age 54; there was no family history of a similar disorder. The mutant protein was barely detectable in brain tissue from the patient, suggesting that it undergoes nonsense-mediated mRNA decay, resulting in haploinsufficiency. In vitro functional expression assays in HEK293 cells showed that the mutant protein did not undergo autophosphorylation, but coexpression of the mutant with wildtype did not suppress wildtype autophosphorylation, indicating that the mutation does not act in a dominant-negative manner. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
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</div>
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|
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</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CSF1R, IVS18DS, G-T, +1
|
|
|
|
|
|
<br />
|
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|
|
SNP: rs587777246,
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|
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|
|
ClinVar: RCV000106404
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|
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|
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese man with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820), Konno et al. (2014) identified a heterozygous G-to-T transversion in intron 18 of the CSF1R gene (c.2442+1G-T), resulting in a splice site mutation. Patient tissue showed 3 aberrant splice variants with skipped exon 18, all resulting in truncated proteins. Western blot analysis of patient brain tissue showed markedly decreased expression of the full-length protein. In vitro functional expression assays in HEK293 cells showed that the mutant protein did not undergo autophosphorylation, but coexpression of the mutant with wildtype did not suppress wildtype autophosphorylation, indicating that the mutation does not act in a dominant-negative manner. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CSF1R, ALA781GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777247,
|
|
|
|
|
|
|
|
ClinVar: RCV000106405
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese woman with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820), Konno et al. (2014) identified a heterozygous c.2342C-A transversion in the CSF1R gene, resulting in an ala781-to-glu (A781E) substitution at a highly conserved residue in the tyrosine kinase domain. The mutation was not found in the dbSNP database or in 124 controls. In vitro functional expression assays in HEK293 cells showed that the mutant protein did not undergo autophosphorylation, but coexpression of the mutant with wildtype did not suppress wildtype autophosphorylation, indicating that the mutation does not act in a dominant-negative manner. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
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|
|
CSF1R, ARG782HIS
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|
|
<br />
|
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|
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SNP: rs281860281,
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|
|
ClinVar: RCV000031932, RCV001561353, RCV002482936
|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family (FTD368) with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820), originally reported by Knopman et al. (1996), Nicholson et al. (2013) identified a heterozygous c.2345G-A transition in exon 18 of the CSF1R gene, resulting in an arg782-to-his (R782H) substitution in the kinase domain. The mutation segregated with the disorder in the family and was not found in 1,089 white, non-Hispanic control individuals. In vitro functional expression studies in HeLa cells showed that the R782H mutation abrogated CSF1R autophosphorylation, which would inhibit downstream signaling. Since the family had originally received a clinicopathologic diagnosis of pigmented orthochromatic leukodystrophy (POLD), the findings indicated that POLD and HDLS are a single disease entity. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</strong>
|
|
</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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CSF1R, PRO132LEU
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<br />
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SNP: rs1351319114,
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ClinVar: RCV000785984, RCV003727825
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a 4-year-old Brazilian boy (family A), with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; 618476), Guo et al. (2019) identified compound heterozygous mutations in the CSF1R gene: a c.395C-T transition (c.395C-T, NM_005211), resulting in a pro132-to-leu (P132L) substitution, and a c.1441C-T transition, resulting in a gln481-to-ter (Q481X; 164770.0011) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The P132L variant was found once in the heterozygous state in the gnomAD database, and c.1441C-T was found in 1 control from 1,200 elderly healthy Brazilians. Analysis of patient cells indicated that the nonsense mutation resulted in nonsense-mediated mRNA decay. In vitro functional expression studies showed that cells carrying the P132L mutation had significantly decreased CSF1R-mediated phosphorylation of JNK (601158), consistent with a loss of function. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</strong>
|
|
</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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CSF1R, GLN481TER
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<br />
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SNP: rs917027829,
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gnomAD: rs917027829,
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ClinVar: RCV000624615, RCV000785985, RCV001849409, RCV001860422
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>For discussion of the c.1441C-T transition (c.1441C-T, NM_005211) in the CSF1R gene, resulting in a gln481-to-ter (Q481X) substitution, that was found in compound heterozygous state in a patient with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; 618476) by Guo et al. (2019), see 164770.0010. </p>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>.0012 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</strong>
|
|
</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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CSF1R, IVS13AS, G-A, -119
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<br />
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SNP: rs1561912628,
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ClinVar: RCV000785986, RCV002469289
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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 37-year-old Japanese woman (family B) with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; 618476), Guo et al. (2019) identified compound heterozygous mutations in the CSF1R gene: a G-to-A transition (c.1859-119G-A, NM_005211) in intron 13, resulting in aberrant splicing, and a 3-bp in-frame deletion (c.1879_1881del; 164770.0013), resulting in the deletion of lys627 in the intracellular kinase domain. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither variant was found in any available database, including gnomAD. Analysis of patient cells showed that the c.1859-119G-A variant resulted in a 117-bp insertion, leading to an elongated protein (Ser620delins40). In vitro functional expression studies showed that cells carrying both of these mutations significantly decreased CSF1R-mediated phosphorylation of JNK (601158), consistent with a loss of function. </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">
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<strong>.0013 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</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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CSF1R, 3-BP DEL, NT1879
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<br />
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SNP: rs1554101963,
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ClinVar: RCV000522082, RCV000785987
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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>For discussion of the 3-bp in-frame deletion (c.1879_1881del, NM_005211) in the CSF1R gene, resulting in the deletion of lys627 in the intracellular kinase domain, that was found in compound heterozygous state in a patient with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; 618476) by Guo et al. (2019), see 164770.0012. </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">
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<strong>.0014 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</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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CSF1R, 2-BP DEL, IVS14, 1969+115_1969+116
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<br />
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SNP: rs1581289103,
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ClinVar: RCV000785988, RCV003329339
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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 2 sibs, born of consanguineous Chaldean parents (family C), with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; 618476), Guo et al. (2019) identified a homozygous 2-bp deletion deep within intron 14 of the CSF1R gene (c.1969+115_1969+116, NM_005211). The variant, which was found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. RT-PCR analysis of patients cells showed an abnormal transcript with a 99-bp insertion, resulting in premature termination (Pro658SerfsTer24). However, the mutation was subject to nonsense-mediated mRNA decay, suggesting a complete loss of function. </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">
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<strong>.0015 BRAIN ABNORMALITIES, NEURODEGENERATION, AND DYSOSTEOSCLEROSIS</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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CSF1R, IVS12AS, G-C, -1
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<br />
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SNP: rs1561913526,
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ClinVar: RCV000785989
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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 male infant, born of consanguineous parents of Native Alaskan ancestry (family CSF1R_01), with brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS; 618476), Oosterhof et al. (2019) identified a homozygous G-to-C transversion (c.1754-1G-C, NM_005211.3) in intron 12 of the CSF1R gene. The mutation, which was found by exome sequencing, segregated with the disorder in the family. The variant was predicted to result in the skipping of exon 13 and produce an in-frame protein product change (Gly585_Lys619delinsAla) within the tyrosine kinase domain. The variant was not found in the ExAC or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed, but the variant was predicted to result in a loss of function. The patient died of bacteremia at 10 months of age. </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">
|
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<strong>.0016 BRAIN ABNORMALITIES AND NEURODEGENERATION WITHOUT DYSOSTEOSCLEROSIS</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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CSF1R, HIS643GLN
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<br />
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SNP: rs184499252,
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gnomAD: rs184499252,
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ClinVar: RCV000785990, RCV003117575
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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 24-year-old man, born of consanguineous Arab parents (family CSF1R_02) with brain abnormalities and neurodegeneration (BANDDOS; 618476), Oosterhof et al. (2019) identified a homozygous c.1929C-A transversion in intron 14 of the CSF1R gene, resulting in a his643-to-gln (H643Q) substitution in the kinase domain. The mutation, which was found by exome sequencing, segregated with the disorder in the family. It was not found in the ExAC or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed, but the variant was predicted to result in a loss of function, most likely with a hypomorphic effect. X-rays showed no evidence of osteopetrosis and there was no known history of hypocalcemia. A similarly affected brother had died at age 21 years, but DNA was not available for study. </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">
|
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<strong>See Also:</strong>
|
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</span>
|
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</h4>
|
|
<span class="mim-text-font">
|
|
Gisselbrecht et al. (1987); Hampe et al. (1984); Verbeek et al.
|
|
(1985); Verbeek et al. (1985); Xu et al. (1985); Yarden and Ullrich
|
|
(1988)
|
|
</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">
|
|
<strong>REFERENCES</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<p />
|
|
</div>
|
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|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aikawa, Y., Katsumoto, T., Zhang, P., Shima, H., Shino, M., Terui, K., Ito, E., Ohno, H., Stanley, E. R., Singh, H., Tenen, D. G., Kitabayashi, I.
|
|
<strong>PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. (Letter)</strong>
|
|
Nature Med. 16: 580-585, 2010.
|
|
|
|
|
|
[PubMed: 20418886]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm.2122]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baba, Y., Ghetti, B., Baker, M. C., Uitti, R. J., Hutton, M. L., Yamaguchi, K., Bird, T., Lin, W., DeLucia, M. W., Dickson, D. W., Wszolek, Z. K.
|
|
<strong>Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred.</strong>
|
|
Acta Neuropath. 111: 300-311, 2006.
|
|
|
|
|
|
[PubMed: 16523341]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00401-006-0046-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Benz-Lemoine, E., Brizard, A., Huret, J.-L., Babin, P., Guilhot, F., Couet, D., Tanzer, J.
|
|
<strong>Malignant histiocytosis: a specific t(2;5)(p23;q35) translocation? Review of the literature.</strong>
|
|
Blood 72: 1045-1047, 1988.
|
|
|
|
|
|
[PubMed: 3416066]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boultwood, J., Rack, K., Kelly, S., Madden, J., Sakaguchi, A. Y., Wang, L.-M., Oscier, D. G., Buckle, V. J., Wainscoat, J. S.
|
|
<strong>Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 6176-6180, 1991.
|
|
|
|
|
|
[PubMed: 1829836]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.14.6176]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dai, X.-M., Zong, X.-H., Akhter, M. P., Stanley, E. R.
|
|
<strong>Osteoclast deficiency results in disorganized matrix, reduced mineralization, and abnormal osteoblast behavior in developing bone.</strong>
|
|
J. Bone Miner. Res. 19: 1441-1451, 2004.
|
|
|
|
|
|
[PubMed: 15312244]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1359/JBMR.040514]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eccles, M. R.
|
|
<strong>Genes encoding the platelet-derived growth factor (PDGF) receptor and colony-stimulating factor 1 (CSF-1) receptor are physically associated in mice as in humans.</strong>
|
|
Gene 108: 285-288, 1991.
|
|
|
|
|
|
[PubMed: 1660841]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0378-1119(91)90447-j]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., Pollard, J. W.
|
|
<strong>Absence of colony-stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits.</strong>
|
|
PLoS One 6: e26317, 2011. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 22046273]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1371/journal.pone.0026317]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Faccio, R., Takeshita, S., Zallone, A., Ross, F. P., Teitelbaum, S. L.
|
|
<strong>c-Fms and the alpha-V-beta-3 integrin collaborate during osteoclast differentiation.</strong>
|
|
J. Clin. Invest. 111: 749-758, 2003.
|
|
|
|
|
|
[PubMed: 12618529]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI16924]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., Samokhvalov, I. M., Merad, M.
|
|
<strong>Fate mapping analysis reveals that adult microglia derive from primitive macrophages.</strong>
|
|
Science 330: 841-845, 2010.
|
|
|
|
|
|
[PubMed: 20966214]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1194637]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gisselbrecht, S., Fichelson, S., Sola, B., Bordereaux, D., Hampe, A., Andre, C., Galibert, F., Tambourin, P. E.
|
|
<strong>Frequent c-fms activation by proviral insertion in mouse myeloblastic leukaemias.</strong>
|
|
Nature 329: 259-261, 1987.
|
|
|
|
|
|
[PubMed: 3476856]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/329259a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Groffen, J., Heisterkamp, N., Spurr, N. K., Dana, S. L., Wasmuth, J. J., Stephenson, J. R.
|
|
<strong>Regional assignment of the human c-fms oncogene to band q34 of chromosome 5. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 37: 484 only, 1984.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 1/8/2013.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., Honjo, R. S., Kim, C. A., and 26 others.
|
|
<strong>Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-Pyle disease spectrum and degenerative encephalopathy with brain malformation.</strong>
|
|
Am. J. Hum. Genet. 104: 925-935, 2019.
|
|
|
|
|
|
[PubMed: 30982609]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2019.03.004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hampe, A., Gobet, M., Sherr, C. J., Galibert, F.
|
|
<strong>Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases.</strong>
|
|
Proc. Nat. Acad. Sci. 81: 85-89, 1984.
|
|
|
|
|
|
[PubMed: 6582485]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.81.1.85]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hampe, A., Shamoon, B.-M., Gobet, M., Sherr, C. J., Galibert, F.
|
|
<strong>Nucleotide sequence and structural organization of the human FMS proto-oncogene.</strong>
|
|
Oncogene Res. 4: 9-17, 1989.
|
|
|
|
|
|
[PubMed: 2524025]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
How, G.-F., Venkatesh, B., Brenner, S.
|
|
<strong>Conserved linkage between the puffer fish (Fugu rubripes) and human genes for platelet-derived growth factor receptor and macrophage colony-stimulating factor receptor.</strong>
|
|
Genome Res. 6: 1185-1191, 1996.
|
|
|
|
|
|
[PubMed: 8973913]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gr.6.12.1185]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Knopman, D., Sung, J. H., Davis, D.
|
|
<strong>Progressive familial leukodystrophy of late onset.</strong>
|
|
Neurology 46: 429-434, 1996.
|
|
|
|
|
|
[PubMed: 8614507]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.46.2.429]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kondo, M., Scherer, D. C., Miyamoto, T., King, A. G., Akashi, K., Sugamura, K., Weissman, I. L.
|
|
<strong>Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines.</strong>
|
|
Nature 407: 383-386, 2000.
|
|
|
|
|
|
[PubMed: 11014194]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/35030112]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Konno, T., Tada, M., Tada, M., Koyama, A., Nozaki, H., Harigaya, Y., Nishimiya, J., Matsunaga, A., Yoshikura, N., Ishihara, K., Arakawa, M., Isami, A., and 11 others.
|
|
<strong>Haploinsufficiency of CSF-1R and clinicopathologic characterization in patients with HDLS.</strong>
|
|
Neurology 82: 139-148, 2014.
|
|
|
|
|
|
[PubMed: 24336230]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0000000000000046]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
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<p class="mim-text-font">
|
|
Lamprecht, B., Walter, K., Kreher, S., Kumar, R., Hummel, M., Lenze, D., Kochert, K., Bouhlel, M. A., Richter, J., Soler, E., Stadhouders, R., Johrens, K., and 13 others.
|
|
<strong>Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma.</strong>
|
|
Nature Med. 16: 571-579, 2010.
|
|
|
|
|
|
[PubMed: 20436485]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm.2129]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Le Beau, M. M., Westbrook, C. A., Diaz, M. O., Larson, R. A., Rowley, J. D., Gasson, J. C., Golde, D. W., Sherr, C. J.
|
|
<strong>Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders.</strong>
|
|
Science 231: 984-987, 1986.
|
|
|
|
|
|
[PubMed: 3484837]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.3484837]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morgan, R., Hecht, B. K., Sandberg, A. A., Hecht, F., Smith, S. D.
|
|
<strong>Chromosome 5q35 breakpoint in malignant histiocytosis. (Letter)</strong>
|
|
New Eng. J. Med. 314: 1322 only, 1986.
|
|
|
|
|
|
[PubMed: 3702936]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/nejm198605153142016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nicholson, A. M., Baker, M. C, Finch, N. A., Rutherford, N. J., Wider, C., Graff-Radford, N. R., Nelson, P. T., Clark, H. B., Wszolek, Z. K., Dickson, D. W., Knopman, D. S., Rademakers, R.
|
|
<strong>CSF1R mutations link POLD and HDLS as a single disease entity.</strong>
|
|
Neurology 80: 1033-1040, 2013.
|
|
|
|
|
|
[PubMed: 23408870]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e31828726a7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oosterhof, N., Chang, I. J., Karimiani, E. G., Kuil, L. E., Jensen, D. M., Daza, R., Young, E., Astle, L., van der Linde, H. C., Shivaram, G. M., Demmers, J., Latimer, C. S., Keene, C. D., Loter, E., Maroofian, R., van Ham, T. J., Hevner, R. F., Bennett, J. T.
|
|
<strong>Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia.</strong>
|
|
Am. J. Hum. Genet. 104: 936-947, 2019.
|
|
|
|
|
|
[PubMed: 30982608]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2019.03.010]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M., Adamson, J., Kouri, N., and 26 others.
|
|
<strong>Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.</strong>
|
|
Nature Genet. 44: 200-205, 2012.
|
|
|
|
|
|
[PubMed: 22197934]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.1027]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ridge, S. A., Worwood, M., Oscier, D., Jacobs, A., Padua, R. A.
|
|
<strong>FMS mutations in myelodysplastic, leukemic, and normal subjects.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 1377-1380, 1990.
|
|
|
|
|
|
[PubMed: 2406720]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.4.1377]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roberts, W. M., Look, A. T., Roussel, M. F., Sherr, C. J.
|
|
<strong>Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes.</strong>
|
|
Cell 55: 655-661, 1988.
|
|
|
|
|
|
[PubMed: 2846185]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(88)90224-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sapi, E., Flick, M. B., Kacinski, B. M.
|
|
<strong>The first intron of human c-fms proto-oncogene contains a processed pseudogene (RPL7P) for ribosomal protein L7.</strong>
|
|
Genomics 22: 641-645, 1994.
|
|
|
|
|
|
[PubMed: 8001978]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1440]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Swerdlow, R. H., Miller, B. B., Lopes, M. B. S., Mandell, J. W., Wooten, G. F., Damgaard, P., Manning, C., Fowler, M., Brashear, H. R.
|
|
<strong>Autosomal dominant subcortical gliosis presenting as frontotemporal dementia.</strong>
|
|
Neurology 72: 260-267, 2009.
|
|
|
|
|
|
[PubMed: 19153373]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000339484.61490.a4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Cong, N., Fichelson, S., Gross, M. S., Sola, B., Bordereaux, D., de Tand, M. F., Guilhot, S., Gisselbrecht, S., Frezal, J., Tambourin, P.
|
|
<strong>The human homologues of Fim1, Fim2/c-Fms, and Fim3, three retroviral integration regions involved in mouse myeloblastic leukemias, are respectively located on chromosomes 6p23, 5q33, and 3q27.</strong>
|
|
Hum. Genet. 81: 257-263, 1989.
|
|
|
|
|
|
[PubMed: 2921036]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00279000]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Cong, N., Fichelson, S., Sola, B., Gross, M. S., Jegou-Foubert, C., Bordereaux, D., Gisselbrecht, S., Tambourin, P. E., Frezal, J.
|
|
<strong>Assignment of Fim-2 (CSF1R) to chromosome 5q33 (in situ hybridization) and Fim-3 to chromosome 3 (somatic cell analysis) region 3q27 (in situ hybridization). (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 670 only, 1987.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verbeek, J. S., Roebroek, A. J. M., van den Ouweland, A. M. W., Bloemers, H. P. J., Van de Ven, W. J. M.
|
|
<strong>Human c-fms proto-oncogene: comparative analysis with an abnormal allele.</strong>
|
|
Molec. Cell. Biol. 5: 422-426, 1985.
|
|
|
|
|
|
[PubMed: 3974576]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.5.2.422-426.1985]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Verbeek, J. S., van Heerikhuizen, H., de Pauw, B. E., Haanen, C., Bloemers, H. P. J., Van de Ven, W. J. M.
|
|
<strong>A hereditary abnormal c-fms proto-oncogene in a patient with acute lymphocytic leukaemia and congenital hypothyroidism.</strong>
|
|
Brit. J. Haemat. 61: 135-138, 1985.
|
|
|
|
|
|
[PubMed: 3863666]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1985.tb04068.x]
|
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</p>
|
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</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Xu, D. Q., Guilhot, S., Galibert, F.
|
|
<strong>Restriction fragment length polymorphism of the human c-fms gene.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 2862-2865, 1985.
|
|
|
|
|
|
[PubMed: 2986142]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.82.9.2862]
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</p>
|
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</li>
|
|
|
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<li>
|
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<p class="mim-text-font">
|
|
Yarden, Y., Ullrich, A.
|
|
<strong>Growth factor receptor tyrosine kinases.</strong>
|
|
Ann. Rev. Biochem. 57: 443-478, 1988.
|
|
|
|
|
|
[PubMed: 3052279]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1146/annurev.bi.57.070188.002303]
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