4511 lines
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Entry
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- *613602 - WD REPEAT-CONTAINING PROTEIN 35; WDR35
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*613602</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#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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<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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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/613602">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<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=ENSG00000118965;t=ENST00000281405" 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=57539" 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=613602" 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 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="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=ENSG00000118965;t=ENST00000281405" 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_001006657,NM_020779,XM_011533007,XM_047445199,XR_426989,XR_939699" 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_020779" 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=613602" 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=15667&isoform_id=15667_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/WDR35" 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/22477171,48474987,50949484,55743161,56243599,62630191,119621243,119621244,119621245,119621246,193783815,193787100,767914961,929654898,2217329862,2462575625,2462575627" 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/Q9P2L0" 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=57539" 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=ENSG00000118965;t=ENST00000281405" 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=WDR35" 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=WDR35" 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+57539" 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/WDR35" 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:57539" 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/57539" 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=chr2&hgg_gene=ENST00000345530.8&hgg_start=19910263&hgg_end=19990105&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://search.clinicalgenome.org/kb/gene-dosage/HGNC:29250" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:29250" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=613602[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=613602[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://gnomad.broadinstitute.org/gene/ENSG00000118965" 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=WDR35" 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=WDR35" 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=WDR35" 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=WDR35&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/PA134928987" 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:29250" 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/FBgn0035264.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:1921932" 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/WDR35#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:1921932" 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/57539/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=57539" 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=WBGene00016935;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-060810-148" 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://reactome.org/content/query?q=WDR35&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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613602
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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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WD REPEAT-CONTAINING PROTEIN 35; WDR35
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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NAOFEN<br />
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INTRAFLAGELLAR TRANSPORT 121, CHLAMYDOMONAS, HOMOLOG OF; IFT121<br />
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KIAA1336
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=WDR35" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">WDR35</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">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/2/71?start=-3&limit=10&highlight=71">2p24.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:19910263-19990105&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'})">2:19,910,263-19,990,105</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=613610,614091" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="2">
|
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<span class="mim-font">
|
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<a href="/geneMap/2/71?start=-3&limit=10&highlight=71">
|
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2p24.1
|
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</a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Cranioectodermal dysplasia 2
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
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<a href="/entry/613610"> 613610 </a>
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</span>
|
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Short-rib thoracic dysplasia 7 with or without polydactyly
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/614091"> 614091 </a>
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/613602" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<p>WDR35 is a WD40 domain-containing protein. Studies in mouse and several lower organisms have implicated WDR35 in intraflagellar transport (summary by <a href="#5" class="mim-tip-reference" title="Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G. <strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong> Am. J. Hum. Genet. 87: 418-423, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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.2010.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20817137">Gilissen et al. (2010)</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20817137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By sequencing clones obtained from a size-fractionated adult brain cDNA library, <a href="#12" class="mim-tip-reference" title="Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 7: 65-73, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10718198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10718198</a>] [<a href="https://doi.org/10.1093/dnares/7.1.65" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10718198">Nagase et al. (2000)</a> obtained a partial WDR35 clone, which they designated KIAA1336. RT-PCR ELISA detected highest expression in adult ovary, followed by testis, kidney, brain, and liver. Low expression was detected in fetal brain and adult heart and lung, with little to no expression in fetal liver and adult skeletal muscle, pancreas, and spleen. Moderate to high expression was detected in all adult brain regions examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10718198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G. <strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong> Am. J. Hum. Genet. 87: 418-423, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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.2010.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20817137">Gilissen et al. (2010)</a> determined that the 1,181-amino acid human WDR35 protein has 4 N-terminal WD40 motifs, a central WD40 motif, and a region of low complexity near the C terminus. They identified 3 additional WDR35 isoforms by database analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20817137" 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>By screening a rat brain/spinal cord expression cDNA library for proteins reactive against anti-shigatoxin antibody, <a href="#4" class="mim-tip-reference" title="Feng, G.-G., Li, C., Huang, L., Tsunekawa, K., Sato, Y., Fujiwara, Y., Komatsu, T., Honda, T., Fan, J.-H., Goto, H., Koide, T., Hasegawa, T., Ishikawa, N. <strong>Naofen, a novel WD40-repeat protein, mediates spontaneous and tumor necrosis factor-induced apoptosis.</strong> Biochem. Biophys. Res. Commun. 394: 153-157, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20193664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20193664</a>] [<a href="https://doi.org/10.1016/j.bbrc.2010.02.133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20193664">Feng et al. (2010)</a> cloned rat Wdr35, which they called Naofen. The deduced 1,170-amino acid protein contains 4 N-terminal WD40 domains and shares 92.7% identity with human WDR35. Quantitative RT-PCR detected Wdr35 expression in all rat tissues examined, with highest expression in testis, followed by brain, and lowest expression in spleen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20193664" 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="Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G. <strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong> Am. J. Hum. Genet. 87: 418-423, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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.2010.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20817137">Gilissen et al. (2010)</a> determined that the WDR35 gene contains 28 coding exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20817137" 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="#6" class="mim-tip-reference" title="Hartz, P. A. <strong>Personal Communication.</strong> Baltimore, Md. 10/12/2010."None>Hartz (2010)</a> mapped the WDR35 gene to chromosome 2p24.1 based on an alignment of the WDR35 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AB037757" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AB037757</a>) with the genomic sequence (GRCh37).</p>
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<p>Using small interfering RNA, <a href="#4" class="mim-tip-reference" title="Feng, G.-G., Li, C., Huang, L., Tsunekawa, K., Sato, Y., Fujiwara, Y., Komatsu, T., Honda, T., Fan, J.-H., Goto, H., Koide, T., Hasegawa, T., Ishikawa, N. <strong>Naofen, a novel WD40-repeat protein, mediates spontaneous and tumor necrosis factor-induced apoptosis.</strong> Biochem. Biophys. Res. Commun. 394: 153-157, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20193664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20193664</a>] [<a href="https://doi.org/10.1016/j.bbrc.2010.02.133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20193664">Feng et al. (2010)</a> showed that knockdown of Naofen in HEK293 cells reduced TNF-alpha (TNF; <a href="/entry/191160">191160</a>)-induced caspase-3 (CASP3; <a href="/entry/600636">600636</a>) activation and apoptosis. Overexpression of rat Naofen spontaneously induced caspase-3 activation and apoptosis and increased cell susceptibility to TNF-alpha-induced apoptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20193664" 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>By immunoblot and immunofluorescence analysis of Wdr35 -/- mouse fibroblasts, <a href="#2" class="mim-tip-reference" title="Caparros-Martin, J. A., De Luca, A., Cartault, F., Aglan, M., Temtamy, S., Otaify, G. A., Mehrez, M., Valencia, M., Vazquez, L., Alessandri, J.-L., Nevado, J., Rudda-Arenas, I., Heath, K. E., Digilio, M. C., Dallapiccola, B., Goodship, J. A., Mill, P., Lapunzina, P., Ruiz-Perez, V. L. <strong>Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium.</strong> Hum. Molec. Genet. 24: 4126-4137, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25908617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25908617</a>] [<a href="https://doi.org/10.1093/hmg/ddv152" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25908617">Caparros-Martin et al. (2015)</a> observed no change in total protein levels of EVC (<a href="/entry/604831">604831</a>) and EVC2 (<a href="/entry/607261">607261</a>) in the mutant fibroblasts compared to controls; however, neither EVC or EVC2 was detected in Wdr35 -/- cilia. In response to the SMO agonist SAG, which drives SMO (SMOH; <a href="/entry/601500">601500</a>) into the ciliary compartment, only Wdr35 -/- cilia remained negative for SMO immunofluorescence. The authors concluded that additional intraflagellar transport complex A (IFTA)-dependent functions requiring WDR35, but not retrograde transport, are specifically required for the correct ciliary entry of EVC, EVC2, and SMO. Levels of IFT43 (<a href="/entry/614068">614068</a>) appeared to depend on WDR35, since IFT43 was strongly reduced in Wdr35 -/- fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25908617" 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><strong><em>Cranioectodermal Dysplasia 2</em></strong></p><p>
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By exome sequencing, <a href="#5" class="mim-tip-reference" title="Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G. <strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong> Am. J. Hum. Genet. 87: 418-423, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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.2010.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20817137">Gilissen et al. (2010)</a> identified compound heterozygous mutations in the WDR35 gene (<a href="#0001">613602.0001</a>-<a href="#0004">613602.0004</a>) in 2 unrelated Dutch children with cranioectodermal dysplasia (CED2; <a href="/entry/613610">613610</a>). Genetic analysis of 6 additional patients with a similar disorder and in 15 patients with Jeune syndrome (<a href="/entry/208500">208500</a>) did not yield any further WDR35 mutations. The authors noted that studies in Drosophila and C. elegans with WDR35 orthologs showed localization to the cilium and function in intraflagellar transport. <a href="#5" class="mim-tip-reference" title="Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G. <strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong> Am. J. Hum. Genet. 87: 418-423, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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.2010.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20817137">Gilissen et al. (2010)</a> postulated that the WDR35 mutations resulted in ciliary dysfunction due to disrupted intraflagellar transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20817137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 4-year-old Mexican boy with CED, <a href="#1" class="mim-tip-reference" title="Bacino, C. A., Dhar, S. U., Brunetti-Pierri, N., Lee, B., Bonnen, P. E. <strong>WDR35 mutation in siblings with Sensenbrenner syndrome: a ciliopathy with variable phenotype.</strong> Am. J. Med. Genet. 158A: 2917-2924, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22987818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22987818</a>] [<a href="https://doi.org/10.1002/ajmg.a.35608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22987818">Bacino et al. (2012)</a> identified homozygosity for a missense mutation in the WDR35 gene (L520P; <a href="#0008">613602.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22987818" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an 8-month-old boy who had CED with multisutural craniosynostoses, <a href="#10" class="mim-tip-reference" title="Lin, A. E., Traum, A. Z., Sahai, I., Keppler-Noreuil, K., Kukolich, M. K., Adam, M. P., Westra, S. J., Arts, H. H. <strong>Sensenbrenner syndrome (cranioectodermal dysplasia): clinical and molecular analyses of 39 patients including two new patients.</strong> Am. J. Med. Genet. 161A: 2762-2776, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24123776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24123776</a>] [<a href="https://doi.org/10.1002/ajmg.a.36265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24123776">Lin et al. (2013)</a> identified compound heterozygosity for missense mutations in the WDR35 gene: H1031Y (<a href="#0009">613602.0009</a>) and Y1068C (<a href="#0010">613602.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24123776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 15-year-old Pakistani boy with relatively mild CED, <a href="#13" class="mim-tip-reference" title="Smith, C., Lamont, R. E., Wade, A., Bernier, F. P., Parboosingh, J. S., Innes, A. M. <strong>A relatively mild skeletal ciliopathy phenotype consistent with cranioectodermal dysplasia is associated with a homozygous nonsynonymous mutation in WDR35.</strong> Am. J. Med. Genet. 170A: 760-765, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26691894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26691894</a>] [<a href="https://doi.org/10.1002/ajmg.a.37514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26691894">Smith et al. (2016)</a> identified homozygosity for a missense mutation in the WR35 gene (W1153C; <a href="#0012">613602.0012</a>). The authors noted that it was the most distal mutation yet reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26691894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 9-year-old Polish girl with Sensenbrenner syndrome, <a href="#15" class="mim-tip-reference" title="Walczak-Sztulpa, J., Wawrocka, A., Sobierajewicz, A., Kuszel, L., Zawadzki, J., Grenda, R., Swiader-Lesniak, A., Kocyla-Karczmarewicz, B., Wnuk, A., Latos-Bielenska, A., Chrzanowska, K. H. <strong>Intrafamilial phenotypic variability in a Polish family with Sensenbrenner syndrome and biallelic WDR35 mutations.</strong> Am. J. Med. Genet. 173A: 1364-1368, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28332779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28332779</a>] [<a href="https://doi.org/10.1002/ajmg.a.38163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28332779">Walczak-Sztulpa et al. (2017)</a> sequenced the candidate genes IFT122 (<a href="/entry/606145">606145</a>) and WDR35 and identified compound heterozygosity for mutations in the WDR35 gene: L641X (<a href="#0015">613602.0015</a>) and D841V (<a href="#0016">613602.0016</a>). The authors noted that this family exhibited intrafamilial variability, in that the proband's affected older sister had a more severe expression of the phenotype and had died in infancy. They suggested that the observed inter- and intrafamilial clinical variability within ciliopathies might be explained by 'mutational load,' including genetic heterogeneity, mutation type, genetic load, modifier effects, and/or oligogenic inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28332779" 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>Short-Rib Thoracic Dysplasia 7 with or without Polydactyly</em></strong></p><p>
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In 2 sibs with short-rib thoracic dysplasia-7 (SRTD7; <a href="/entry/614091">614091</a>), <a href="#11" class="mim-tip-reference" title="Mill, P., Lockhart, P. J., Fitzpatrick, E., Mountford, H. S., Hall, E. A., Reijns, M. A. M., Keighren, M., Bahlo, M., Bromhead, C. J., Budd, P., Aftimos, S., Delatycki, M. B., Savarirayan, R., Jackson, I. J., Amor, D. J. <strong>Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis.</strong> Am. J. Hum. Genet. 88: 508-515, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21473986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21473986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21473986[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.2011.03.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21473986">Mill et al. (2011)</a> identified a homozygous deletion mutation in the WDR35 gene (<a href="#0005">613602.0005</a>). In an unrelated fetus with SRTD7, they identified compound heterozygous mutations in the WDR35 gene (<a href="#0006">613602.0006</a>-<a href="#0007">613602.0007</a>). All 3 patients exhibited polydactyly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21473986" 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 5 children from 3 unrelated families exhibiting a distinctive form of SRTD with overlapping features of both Ellis-van Creveld syndrome (see <a href="/entry/225500">225500</a>) and cranioectodermal dysplasia, <a href="#2" class="mim-tip-reference" title="Caparros-Martin, J. A., De Luca, A., Cartault, F., Aglan, M., Temtamy, S., Otaify, G. A., Mehrez, M., Valencia, M., Vazquez, L., Alessandri, J.-L., Nevado, J., Rudda-Arenas, I., Heath, K. E., Digilio, M. C., Dallapiccola, B., Goodship, J. A., Mill, P., Lapunzina, P., Ruiz-Perez, V. L. <strong>Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium.</strong> Hum. Molec. Genet. 24: 4126-4137, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25908617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25908617</a>] [<a href="https://doi.org/10.1093/hmg/ddv152" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25908617">Caparros-Martin et al. (2015)</a> identified biallelic mutations in the WDR35 gene (see, e.g., <a href="#0011">613602.0011</a>). All of the mutations were shown to affect splicing of WDR35. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25908617" 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 3 sibs and an unrelated female infant with an unusual form of SRTD involving bent ribs and long bones as well as undermineralization of the skull, <a href="#3" class="mim-tip-reference" title="Duran, I., Taylor, S. P., Zhang, W., Martin, J., Qureshi, F., Jacques, S. M., Wallerstein, R., Lachman, R. S., Nickerson, D. A., Bamshad, M., Cohn, D. H., Krakow, D. <strong>Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia.</strong> Cilia 6: 7, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28400947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28400947</a>] [<a href="https://doi.org/10.1186/s13630-017-0051-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28400947">Duran et al. (2017)</a> performed exome analysis and in both families identified compound heterozygosity for a missense mutation and a truncating mutation (see, e.g., <a href="#0013">613602.0013</a> and <a href="#0014">613602.0014</a>). The sibs had polydactyly, whereas the unrelated female infant did not. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28400947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Toriyama, M., Lee, C., Taylor, S. P., Duran, I., Cohn, D. H., Bruel, A.-L., Tabler, J. M., Drew, K., Kelly, M. R., Kim, S., Park, T. J., Braun, D. A., and 21 others. <strong>The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.</strong> Nature Genet. 48: 648-656, 2016. Note: Erratum: Nature Genet. 48: 970 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27158779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27158779</a>] [<a href="https://doi.org/10.1038/ng.3558" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27158779">Toriyama et al. (2016)</a> reported a male infant with SRTD and polydactyly due to apparent digenic inheritance; the infant exhibited double heterozygosity for a truncating mutation in the INTU gene (Q276X; <a href="/entry/610621#0003">610621.0003</a>) and a missense mutation in WDR35 (W311L; <a href="#0013">613602.0013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27158779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a mouse mutation screen for developmental phenotypes, <a href="#11" class="mim-tip-reference" title="Mill, P., Lockhart, P. J., Fitzpatrick, E., Mountford, H. S., Hall, E. A., Reijns, M. A. M., Keighren, M., Bahlo, M., Bromhead, C. J., Budd, P., Aftimos, S., Delatycki, M. B., Savarirayan, R., Jackson, I. J., Amor, D. J. <strong>Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis.</strong> Am. J. Hum. Genet. 88: 508-515, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21473986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21473986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21473986[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.2011.03.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21473986">Mill et al. (2011)</a> identified a mutation in the Wdr35 gene as the cause of midgestation lethality, with abnormalities characteristic of defects in the Hedgehog signaling pathway. <a href="#11" class="mim-tip-reference" title="Mill, P., Lockhart, P. J., Fitzpatrick, E., Mountford, H. S., Hall, E. A., Reijns, M. A. M., Keighren, M., Bahlo, M., Bromhead, C. J., Budd, P., Aftimos, S., Delatycki, M. B., Savarirayan, R., Jackson, I. J., Amor, D. J. <strong>Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis.</strong> Am. J. Hum. Genet. 88: 508-515, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21473986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21473986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21473986[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.2011.03.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21473986">Mill et al. (2011)</a> showed that endogenous WDR35 localizes to cilia and centrosomes throughout the developing embryo and that human and mouse fibroblasts lacking the protein fail to produce cilia. Through structural modeling, <a href="#11" class="mim-tip-reference" title="Mill, P., Lockhart, P. J., Fitzpatrick, E., Mountford, H. S., Hall, E. A., Reijns, M. A. M., Keighren, M., Bahlo, M., Bromhead, C. J., Budd, P., Aftimos, S., Delatycki, M. B., Savarirayan, R., Jackson, I. J., Amor, D. J. <strong>Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis.</strong> Am. J. Hum. Genet. 88: 508-515, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21473986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21473986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21473986[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.2011.03.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21473986">Mill et al. (2011)</a> showed that WDR35 has strong homology to the COPI coatamers involved in vesicular trafficking and that human SRPS mutations affect key structural elements in WDR35. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21473986" 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> rs397515534 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515534;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/rs397515534?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=rs397515534" 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=rs397515534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Dutch child with cranioectodermal dysplasia-2 (CED2; <a href="/entry/613610">613610</a>), <a href="#5" class="mim-tip-reference" title="Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G. <strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong> Am. J. Hum. Genet. 87: 418-423, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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.2010.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20817137">Gilissen et al. (2010)</a> identified compound heterozygosity for 2 mutations in the WDR35 gene: an A-to-G transition in intron 2 (25-2A-G) resulting in a splice site mutation and premature termination, and a 1877A-G transition in exon 17 resulting in a glu626-to-gly (E626G; <a href="#0002">613602.0002</a>) substitution at a highly conserved residue. Neither mutation was found in 210 control alleles. The phenotype included short stature, dolichocephaly, craniosynostosis, narrow thorax with pectus excavatum, short limbs, and brachydactyly. Facial features included narrow palpebral fissures, telecanthus with hypertelorism, low-set simple ears, everted lower lip, and short neck. Teeth abnormalities included widely spaced, hypoplastic, and fused teeth. The boy also had joint laxity, inguinal hernia, and webbed fingers. There was no evidence of renal or hepatic disease, and he had normal intelligence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20817137" 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">rs267607174 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607174;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=rs267607174" 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=rs267607174" 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=RCV000000038" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000038" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000038</a>
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<p>For discussion of the glu626-to-gly (E626G) mutation in the WDR35 gene that was found in compound heterozygous state in a patient with cranioectodermal dysplasia-2 (CED2; <a href="/entry/613610">613610</a>) by <a href="#5" class="mim-tip-reference" title="Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G. <strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong> Am. J. Hum. Genet. 87: 418-423, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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.2010.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20817137">Gilissen et al. (2010)</a>, see <a href="#0001">613602.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20817137" 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> rs397515334 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515334;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/rs397515334?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=rs397515334" 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=rs397515334" 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=RCV000000039 OR RCV005024976" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000039, RCV005024976" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000039...</a>
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<p>In a Dutch child with cranioectodermal dysplasia-2 (CED2; <a href="/entry/613610">613610</a>), <a href="#5" class="mim-tip-reference" title="Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G. <strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong> Am. J. Hum. Genet. 87: 418-423, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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.2010.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20817137">Gilissen et al. (2010)</a> identified compound heterozygosity for 2 mutations in the WDR35 gene: a 1-bp deletion (2891delC) in exon 25 resulting in a frameshift and premature termination, and a 2623G-A transition in exon 23 resulting in an ala875-to-thr (A875T; <a href="#0004">613602.0004</a>) substitution at a highly conserved region. Neither mutation was found in 210 control alleles. The phenotype included short stature, dolichocephaly, craniosynostosis, narrow thorax with pectus excavatum, short limbs, and brachydactyly. Facial features included narrow palpebral fissures, telecanthus with hypertelorism, low-set simple ears, everted lower lip, and short neck. Teeth abnormalities included widely spaced, hypoplastic, and fused teeth. The boy also had joint laxity, inguinal hernia, and webbed fingers. There was no evidence of renal or hepatic disease, and he had normal intelligence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20817137" 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 CRANIOECTODERMAL DYSPLASIA 2</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> rs267607175 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607175;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/rs267607175?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=rs267607175" 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=rs267607175" 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=RCV000000040 OR RCV000508347" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000040, RCV000508347" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000040...</a>
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<p>For discussion of the ala875-to-thr (A875T) mutation in the WDR35 gene that was found in compound heterozygous state in a patient with cranioectodermal dysplasia-2 (CED2; <a href="/entry/613610">613610</a>) by <a href="#5" class="mim-tip-reference" title="Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G. <strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong> Am. J. Hum. Genet. 87: 418-423, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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.2010.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20817137">Gilissen et al. (2010)</a>, see <a href="#0003">613602.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20817137" 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>.0005 SHORT-RIB THORACIC DYSPLASIA 7 WITH POLYDACTYLY</strong>
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WDR35, 2,847-BP DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000024037" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024037" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024037</a>
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<p>In 2 sibs with short-rib thoracic dysplasia-7 with polydactyly (SRTD7; <a href="/entry/614091">614091</a>), who were originally reported by <a href="#8" class="mim-tip-reference" title="Kannu, P., mcFarlane, J. H., Savarirayan, R., Aftimos, S. <strong>An unclassifiable short rib-polydactyly syndrome with acromesomelic hypomineralization and campomelia in siblings.</strong> Am. J. Med. Genet. 143A: 2607-2611, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935248</a>] [<a href="https://doi.org/10.1002/ajmg.a.31989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17935248">Kannu et al. (2007)</a>, <a href="#11" class="mim-tip-reference" title="Mill, P., Lockhart, P. J., Fitzpatrick, E., Mountford, H. S., Hall, E. A., Reijns, M. A. M., Keighren, M., Bahlo, M., Bromhead, C. J., Budd, P., Aftimos, S., Delatycki, M. B., Savarirayan, R., Jackson, I. J., Amor, D. J. <strong>Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis.</strong> Am. J. Hum. Genet. 88: 508-515, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21473986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21473986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21473986[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.2011.03.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21473986">Mill et al. (2011)</a> identified an in-frame homozygous 2,847-bp deletion spanning exon 5 of the WDR35 gene. Both parents and an unaffected sib were heterozygous for the deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21473986+17935248" 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 SHORT-RIB THORACIC DYSPLASIA 7 WITH POLYDACTYLY</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> rs387907085 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907085;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/rs387907085?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=rs387907085" 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=rs387907085" 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=RCV000024038" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024038" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024038</a>
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<p>In a fetus with short-rib thoracic dysplasia-7 with polydactyly (SRTD7; <a href="/entry/614091">614091</a>), <a href="#11" class="mim-tip-reference" title="Mill, P., Lockhart, P. J., Fitzpatrick, E., Mountford, H. S., Hall, E. A., Reijns, M. A. M., Keighren, M., Bahlo, M., Bromhead, C. J., Budd, P., Aftimos, S., Delatycki, M. B., Savarirayan, R., Jackson, I. J., Amor, D. J. <strong>Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis.</strong> Am. J. Hum. Genet. 88: 508-515, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21473986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21473986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21473986[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.2011.03.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21473986">Mill et al. (2011)</a> identified compound heterozygosity for 2 mutations in the WDR35 gene: a 1633C-T transition resulting in an arg545-to-ter (R545X) substitution, and a 781T-C transition resulting in a trp261-to-arg (W261R) substitution (<a href="#0007">613602.0007</a>). The nonsense mutation was inherited from the mother and the missense mutation from the father. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21473986" 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 SHORT-RIB THORACIC DYSPLASIA 7 WITH POLYDACTYLY</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> rs431905505 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs431905505;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/rs431905505?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=rs431905505" 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=rs431905505" 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=RCV000024039" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024039" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024039</a>
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<p>For discussion of the trp261-to-arg (W261R) mutation that was found in compound heterozygous state in a fetus with short-rib thoracic dysplasia-7 (SRTD7; <a href="/entry/614091">614091</a>) by <a href="#11" class="mim-tip-reference" title="Mill, P., Lockhart, P. J., Fitzpatrick, E., Mountford, H. S., Hall, E. A., Reijns, M. A. M., Keighren, M., Bahlo, M., Bromhead, C. J., Budd, P., Aftimos, S., Delatycki, M. B., Savarirayan, R., Jackson, I. J., Amor, D. J. <strong>Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis.</strong> Am. J. Hum. Genet. 88: 508-515, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21473986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21473986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21473986[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.2011.03.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21473986">Mill et al. (2011)</a>, see <a href="#0006">613602.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21473986" 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 CRANIOECTODERMAL DYSPLASIA 2</strong>
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WDR35, LEU520PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397515533 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515533;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=rs397515533" 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=rs397515533" 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=RCV000055831" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000055831" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000055831</a>
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<p>In a 4-year-old Mexican boy with cranioectodermal dysplasia-2 (CED2; <a href="/entry/613610">613610</a>), <a href="#1" class="mim-tip-reference" title="Bacino, C. A., Dhar, S. U., Brunetti-Pierri, N., Lee, B., Bonnen, P. E. <strong>WDR35 mutation in siblings with Sensenbrenner syndrome: a ciliopathy with variable phenotype.</strong> Am. J. Med. Genet. 158A: 2917-2924, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22987818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22987818</a>] [<a href="https://doi.org/10.1002/ajmg.a.35608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22987818">Bacino et al. (2012)</a> identified homozygosity for an A-to-G transition (chr2.20,146,297A-G, GRCh37) in exon 16 of the WDR35 gene, resulting in a leu520-to-pro (L520P) substitution at a highly conserved residue. The unaffected parents and 2 unaffected sibs were heterozygous for the mutation, which was not found in the 1000 Genomes Project, NHLBI Exome Sequencing Project, or NIEHS EGP databases. DNA was unavailable from 3 more affected sibs in the family, including 2 who died at 9 months and 13 months of age, and an affected fetus terminated at 21 weeks' gestation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22987818" 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 CRANIOECTODERMAL DYSPLASIA 2</strong>
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WDR35, HIS1031TYR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1553316264 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553316264;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=rs1553316264" 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=rs1553316264" 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=RCV000578480" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000578480" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000578480</a>
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<p>In an 8-month-old boy with cranioectodermal dysplasia-2 (CED2; <a href="/entry/613610">613610</a>), who had a 'cloverleaf' skull due to multiple suture synostoses, <a href="#10" class="mim-tip-reference" title="Lin, A. E., Traum, A. Z., Sahai, I., Keppler-Noreuil, K., Kukolich, M. K., Adam, M. P., Westra, S. J., Arts, H. H. <strong>Sensenbrenner syndrome (cranioectodermal dysplasia): clinical and molecular analyses of 39 patients including two new patients.</strong> Am. J. Med. Genet. 161A: 2762-2776, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24123776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24123776</a>] [<a href="https://doi.org/10.1002/ajmg.a.36265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24123776">Lin et al. (2013)</a> identified compound heterozygosity for a c.3091C-T transition (c.3091C-T, NM_001006657) in exon 26 of the WDR35 gene, resulting in a his1031-to-tyr (H1031Y) substitution, and a c.3203A-G transition in exon 27, resulting in a tyr1068-to-cys (Y1068C; <a href="#0010">613602.0010</a>) substitution. His unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in public variant databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24123776" 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="0010" class="mim-anchor"></a>
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<strong>.0010 CRANIOECTODERMAL DYSPLASIA 2</strong>
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WDR35, TYR1068CYS
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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> rs541910371 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs541910371;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/rs541910371?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=rs541910371" 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=rs541910371" 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=RCV000507380 OR RCV000578488 OR RCV001266500 OR RCV005027590" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000507380, RCV000578488, RCV001266500, RCV005027590" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000507380...</a>
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<p>For discussion of the c.3203A-G transition (c.3203A-G, NM_001006657) in exon 27 of the WDR35 gene, resulting in a tyr1068-to-cys (Y2068C) substitution, that was found in compound heterozygous state in an 8-month-old boy with cranioectodermal dysplasia-2 (CED2; <a href="/entry/613610">613610</a>) by <a href="#10" class="mim-tip-reference" title="Lin, A. E., Traum, A. Z., Sahai, I., Keppler-Noreuil, K., Kukolich, M. K., Adam, M. P., Westra, S. J., Arts, H. H. <strong>Sensenbrenner syndrome (cranioectodermal dysplasia): clinical and molecular analyses of 39 patients including two new patients.</strong> Am. J. Med. Genet. 161A: 2762-2776, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24123776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24123776</a>] [<a href="https://doi.org/10.1002/ajmg.a.36265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24123776">Lin et al. (2013)</a>, see <a href="#0009">613602.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24123776" 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>.0011 SHORT-RIB THORACIC DYSPLASIA 7 WITH POLYDACTYLY</strong>
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WDR35, IVS2AS, T-A, -18
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1553324519 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553324519;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=rs1553324519" 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=rs1553324519" 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=RCV000578492" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000578492" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000578492</a>
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<p>In 2 affected brothers with short-rib thoracic dysplasia and polydactyly (SRTD7; <a href="/entry/614091">614091</a>), born of first-cousin parents from Reunion Island, <a href="#2" class="mim-tip-reference" title="Caparros-Martin, J. A., De Luca, A., Cartault, F., Aglan, M., Temtamy, S., Otaify, G. A., Mehrez, M., Valencia, M., Vazquez, L., Alessandri, J.-L., Nevado, J., Rudda-Arenas, I., Heath, K. E., Digilio, M. C., Dallapiccola, B., Goodship, J. A., Mill, P., Lapunzina, P., Ruiz-Perez, V. L. <strong>Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium.</strong> Hum. Molec. Genet. 24: 4126-4137, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25908617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25908617</a>] [<a href="https://doi.org/10.1093/hmg/ddv152" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25908617">Caparros-Martin et al. (2015)</a> identified homozygosity for a splice site mutation (c.143-18T-A, NM_001006657.1) in intron 2 of the WDR35 gene. The brothers died of cardiorespiratory failure at ages 5 months and 13 months. Their unaffected parents were heterozygous for the mutation, which was not found in an unaffected brother or in the 1000 Genomes Project, NHLBI Exome Variant Server, or ExAC databases. RT-PCR of peripheral blood RNA from the parents revealed a small cDNA fragment that corresponded to skipping of exon 3, and analysis of transfected COS-7 cells confirmed no inclusion of exon 3 in amplified products. Experiments in transfected COS-7 cells using minigene constructs suggested that the mutation generates an intronic splicing silencer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25908617" 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="0012" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0012 CRANIOECTODERMAL DYSPLASIA 2</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">rs1553313859 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553313859;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=rs1553313859" 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=rs1553313859" 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=RCV000578479" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000578479" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000578479</a>
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<p>In a 15-year-old boy with cranioectodermal dysplasia-2 (CED2; <a href="/entry/613610">613610</a>), born of fourth-cousin Pakistani parents, <a href="#13" class="mim-tip-reference" title="Smith, C., Lamont, R. E., Wade, A., Bernier, F. P., Parboosingh, J. S., Innes, A. M. <strong>A relatively mild skeletal ciliopathy phenotype consistent with cranioectodermal dysplasia is associated with a homozygous nonsynonymous mutation in WDR35.</strong> Am. J. Med. Genet. 170A: 760-765, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26691894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26691894</a>] [<a href="https://doi.org/10.1002/ajmg.a.37514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26691894">Smith et al. (2016)</a> identified homozygosity for a c.3459G-T transversion (c.3459G-T, NM_0010066575.1) in exon 28 of the WDR35 gene, resulting in a trp1153-to-cys (W1153C) substitution at a highly conserved residue. The mutation was not found in the dbSNP, Exome Variant Server, or ExAC databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26691894" 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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SHORT-RIB THORACIC DYSPLASIA 7/20 WITH POLYDACTYLY, DIGENIC, INCLUDED (1 patient)
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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> rs200649783 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200649783;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/rs200649783?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=rs200649783" 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=rs200649783" 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=RCV000516065 OR RCV000578486 OR RCV000608080 OR RCV000755748 OR RCV000851218 OR RCV001353118 OR RCV001764511" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000516065, RCV000578486, RCV000608080, RCV000755748, RCV000851218, RCV001353118, RCV001764511" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000516065...</a>
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<p>In a female infant (R10-483A) with short-rib thoracic dysplasia (SRTD7; <a href="/entry/614091">614091</a>), who did not exhibit polydactyly and died at 1 week of life, <a href="#3" class="mim-tip-reference" title="Duran, I., Taylor, S. P., Zhang, W., Martin, J., Qureshi, F., Jacques, S. M., Wallerstein, R., Lachman, R. S., Nickerson, D. A., Bamshad, M., Cohn, D. H., Krakow, D. <strong>Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia.</strong> Cilia 6: 7, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28400947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28400947</a>] [<a href="https://doi.org/10.1186/s13630-017-0051-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28400947">Duran et al. (2017)</a> identified compound heterozygosity for a c.932G-T transversion in the WDR35 gene, resulting in a trp311-to-leu (W311L) substitution, and a 1-bp deletion (c.1501delC; <a href="#0014">613602.0014</a>), predicted to result in a premature termination codon (Gly501LysfsTer10). Analysis of cultured patient chondrocytes showed decreased IFT43 (<a href="/entry/614068">614068</a>) levels. In addition, there was a reduction in the percentage of cilia present on patient chondrocytes compared to controls, and the mutant cilia showed reduced lengths and were abnormally shaped. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28400947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a male infant (R04-176A) with SRTD and polydactyly, <a href="#14" class="mim-tip-reference" title="Toriyama, M., Lee, C., Taylor, S. P., Duran, I., Cohn, D. H., Bruel, A.-L., Tabler, J. M., Drew, K., Kelly, M. R., Kim, S., Park, T. J., Braun, D. A., and 21 others. <strong>The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.</strong> Nature Genet. 48: 648-656, 2016. Note: Erratum: Nature Genet. 48: 970 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27158779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27158779</a>] [<a href="https://doi.org/10.1038/ng.3558" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27158779">Toriyama et al. (2016)</a> identified double heterozygosity for the W311L mutation in the WDR35 gene and a truncating mutation in the INTU gene (Q276X; <a href="/entry/610621#0003">610621.0003</a>). The patient died in the neonatal period. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27158779" 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> rs886044119 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886044119;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/rs886044119?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=rs886044119" 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=rs886044119" 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=RCV000323877 OR RCV000578495 OR RCV000851219 OR RCV002518074" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000323877, RCV000578495, RCV000851219, RCV002518074" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000323877...</a>
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<p>For discussion of the 1-bp deletion (c.1501delC) in the WDR35 gene, resulting in a premature termination codon (Gln501LysfsTer10), that was found in compound heterozygous state in an infant with short-rib thoracic dysplasia (SRTD7; <a href="/entry/614091">614091</a>) by <a href="#3" class="mim-tip-reference" title="Duran, I., Taylor, S. P., Zhang, W., Martin, J., Qureshi, F., Jacques, S. M., Wallerstein, R., Lachman, R. S., Nickerson, D. A., Bamshad, M., Cohn, D. H., Krakow, D. <strong>Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia.</strong> Cilia 6: 7, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28400947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28400947</a>] [<a href="https://doi.org/10.1186/s13630-017-0051-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28400947">Duran et al. (2017)</a>, see <a href="#0013">613602.0013</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28400947" 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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WDR35, LEU641TER (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199952377;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs199952377</a>)
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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> rs199952377 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199952377;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/rs199952377?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=rs199952377" 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=rs199952377" 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=RCV000055830 OR RCV000288028 OR RCV000515864 OR RCV000648351 OR RCV000826131 OR RCV001557398" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000055830, RCV000288028, RCV000515864, RCV000648351, RCV000826131, RCV001557398" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000055830...</a>
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<p>In a 9-year-old Polish girl with Sensenbrenner syndrome (CED2; <a href="/entry/613610">613610</a>), <a href="#15" class="mim-tip-reference" title="Walczak-Sztulpa, J., Wawrocka, A., Sobierajewicz, A., Kuszel, L., Zawadzki, J., Grenda, R., Swiader-Lesniak, A., Kocyla-Karczmarewicz, B., Wnuk, A., Latos-Bielenska, A., Chrzanowska, K. H. <strong>Intrafamilial phenotypic variability in a Polish family with Sensenbrenner syndrome and biallelic WDR35 mutations.</strong> Am. J. Med. Genet. 173A: 1364-1368, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28332779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28332779</a>] [<a href="https://doi.org/10.1002/ajmg.a.38163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28332779">Walczak-Sztulpa et al. (2017)</a> identified compound heterozygosity for mutations in the WDR35 gene: a c.1922T-G transversion in exon 18, resulting in a leu641-to-ter (L641X) substitution, and a c.2522A-T transversion in exon 22, resulting in an asp841-to-val (D841V; <a href="#0016">613602.0016</a>) substitution. Her unaffected parents were each heterozygous for 1 of the mutations; DNA was unavailable from her affected older sister, who had died in infancy from respiratory, hepatic, and renal insufficiency. The authors noted that the nonsense mutation (L641X) had previously been reported in 2 patients with Sensenbrenner syndrome (<a href="#7" class="mim-tip-reference" title="Hoffer, J. L., Fryssira, H., Konstantinidou, A. E., Ropers, H. H., Tzschach, A. <strong>Novel WDR35 mutations in patients with cranioectodermal dysplasia (Sensenbrenner syndrome). (Letter)</strong> Clin. Genet. 83: 92-95, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22486404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22486404</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2012.01880.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22486404">Hoffer et al., 2013</a>; <a href="#9" class="mim-tip-reference" title="Li, Y., Garrod, A. S., Madan-Khetarpal, S., Sreedher, G., McGuire, M., Yagi, H., Klena, N. T., Gabriel, G. C., Khalifa, O., Zahid, M., Panigrahy, A., Weiner, D. J., Lo, C. W. <strong>Respiratory motile cilia dysfunction in a patient with cranioectodermal dysplasia.</strong> Am. J. Med. Genet. 167A: 2188-2196, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25914204/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25914204</a>] [<a href="https://doi.org/10.1002/ajmg.a.37133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25914204">Li et al., 2015</a>) and was present in the ExAC and UCSC Genome Browser databases at an allele frequency of 0.018% and 0.15%, respectively. The missense mutation (D841V) is located at a highly conserved residue and was not found in the 1000 Genomes Project, NHLBI Exome Variant Server, or ExAC databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25914204+28332779+22486404" 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="Bacino2012" class="mim-anchor"></a>
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Bacino, C. A., Dhar, S. U., Brunetti-Pierri, N., Lee, B., Bonnen, P. E.
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<strong>WDR35 mutation in siblings with Sensenbrenner syndrome: a ciliopathy with variable phenotype.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22987818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22987818</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22987818" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.35608" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
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<a id="Caparros-Martin2015" class="mim-anchor"></a>
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<div class="">
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Caparros-Martin, J. A., De Luca, A., Cartault, F., Aglan, M., Temtamy, S., Otaify, G. A., Mehrez, M., Valencia, M., Vazquez, L., Alessandri, J.-L., Nevado, J., Rudda-Arenas, I., Heath, K. E., Digilio, M. C., Dallapiccola, B., Goodship, J. A., Mill, P., Lapunzina, P., Ruiz-Perez, V. L.
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<strong>Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium.</strong>
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Hum. Molec. Genet. 24: 4126-4137, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25908617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25908617</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25908617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddv152" target="_blank">Full Text</a>]
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<a id="Duran2017" class="mim-anchor"></a>
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Duran, I., Taylor, S. P., Zhang, W., Martin, J., Qureshi, F., Jacques, S. M., Wallerstein, R., Lachman, R. S., Nickerson, D. A., Bamshad, M., Cohn, D. H., Krakow, D.
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<strong>Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia.</strong>
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Cilia 6: 7, 2017. Note: Electronic Article.
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[<a href="https://doi.org/10.1186/s13630-017-0051-y" target="_blank">Full Text</a>]
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<a id="Feng2010" class="mim-anchor"></a>
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Feng, G.-G., Li, C., Huang, L., Tsunekawa, K., Sato, Y., Fujiwara, Y., Komatsu, T., Honda, T., Fan, J.-H., Goto, H., Koide, T., Hasegawa, T., Ishikawa, N.
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<strong>Naofen, a novel WD40-repeat protein, mediates spontaneous and tumor necrosis factor-induced apoptosis.</strong>
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Biochem. Biophys. Res. Commun. 394: 153-157, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20193664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20193664</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20193664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.bbrc.2010.02.133" target="_blank">Full Text</a>]
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<a id="Gilissen2010" class="mim-anchor"></a>
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Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., van Lier, B., Steehouwer, M., van Reeuwijk, J., Kant, S. G., Roepman, R., Knoers, N. V. A. M., Veltman, J. A., Brunner, H. G.
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<strong>Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20817137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20817137</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20817137[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=20817137" 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.2010.08.004" target="_blank">Full Text</a>]
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<strong>Novel WDR35 mutations in patients with cranioectodermal dysplasia (Sensenbrenner syndrome). (Letter)</strong>
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[<a href="https://doi.org/10.1111/j.1399-0004.2012.01880.x" target="_blank">Full Text</a>]
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Kannu, P., mcFarlane, J. H., Savarirayan, R., Aftimos, S.
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<strong>An unclassifiable short rib-polydactyly syndrome with acromesomelic hypomineralization and campomelia in siblings.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935248</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17935248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.31989" target="_blank">Full Text</a>]
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<a id="Li2015" class="mim-anchor"></a>
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Li, Y., Garrod, A. S., Madan-Khetarpal, S., Sreedher, G., McGuire, M., Yagi, H., Klena, N. T., Gabriel, G. C., Khalifa, O., Zahid, M., Panigrahy, A., Weiner, D. J., Lo, C. W.
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<strong>Respiratory motile cilia dysfunction in a patient with cranioectodermal dysplasia.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25914204/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25914204</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25914204" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.37133" target="_blank">Full Text</a>]
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<a id="Lin2013" class="mim-anchor"></a>
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Lin, A. E., Traum, A. Z., Sahai, I., Keppler-Noreuil, K., Kukolich, M. K., Adam, M. P., Westra, S. J., Arts, H. H.
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<strong>Sensenbrenner syndrome (cranioectodermal dysplasia): clinical and molecular analyses of 39 patients including two new patients.</strong>
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Am. J. Med. Genet. 161A: 2762-2776, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24123776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24123776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24123776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.36265" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Mill2011" class="mim-anchor"></a>
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Mill, P., Lockhart, P. J., Fitzpatrick, E., Mountford, H. S., Hall, E. A., Reijns, M. A. M., Keighren, M., Bahlo, M., Bromhead, C. J., Budd, P., Aftimos, S., Delatycki, M. B., Savarirayan, R., Jackson, I. J., Amor, D. J.
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<strong>Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis.</strong>
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Am. J. Hum. Genet. 88: 508-515, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21473986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21473986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21473986[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=21473986" 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.2011.03.015" target="_blank">Full Text</a>]
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Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.</strong>
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[<a href="https://doi.org/10.1093/dnares/7.1.65" target="_blank">Full Text</a>]
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<a id="Smith2016" class="mim-anchor"></a>
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Smith, C., Lamont, R. E., Wade, A., Bernier, F. P., Parboosingh, J. S., Innes, A. M.
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<strong>A relatively mild skeletal ciliopathy phenotype consistent with cranioectodermal dysplasia is associated with a homozygous nonsynonymous mutation in WDR35.</strong>
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Am. J. Med. Genet. 170A: 760-765, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26691894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26691894</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26691894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.37514" target="_blank">Full Text</a>]
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Toriyama, M., Lee, C., Taylor, S. P., Duran, I., Cohn, D. H., Bruel, A.-L., Tabler, J. M., Drew, K., Kelly, M. R., Kim, S., Park, T. J., Braun, D. A., and 21 others.
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<strong>The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.</strong>
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Nature Genet. 48: 648-656, 2016. Note: Erratum: Nature Genet. 48: 970 only, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27158779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27158779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27158779" 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.3558" target="_blank">Full Text</a>]
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<a id="Walczak-Sztulpa2017" class="mim-anchor"></a>
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Walczak-Sztulpa, J., Wawrocka, A., Sobierajewicz, A., Kuszel, L., Zawadzki, J., Grenda, R., Swiader-Lesniak, A., Kocyla-Karczmarewicz, B., Wnuk, A., Latos-Bielenska, A., Chrzanowska, K. H.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28332779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28332779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28332779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.38163" 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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Marla J. F. O'Neill - updated : 03/30/2018
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 02/06/2018<br>Nara Sobreira - updated : 7/15/2011<br>Cassandra L. Kniffin - updated : 10/21/2010
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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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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Patricia A. Hartz : 10/13/2010
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</span>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </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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alopez : 09/24/2020
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<span class="mim-text-font">
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carol : 04/02/2018<br>carol : 03/30/2018<br>carol : 02/08/2018<br>carol : 02/07/2018<br>carol : 02/06/2018<br>mcolton : 07/30/2015<br>carol : 2/10/2014<br>carol : 9/9/2013<br>terry : 7/18/2011<br>carol : 7/15/2011<br>mgross : 6/29/2011<br>wwang : 10/26/2010<br>ckniffin : 10/21/2010<br>mgross : 10/13/2010
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<h3>
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<span class="mim-font">
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<strong>*</strong> 613602
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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WD REPEAT-CONTAINING PROTEIN 35; WDR35
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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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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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NAOFEN<br />
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INTRAFLAGELLAR TRANSPORT 121, CHLAMYDOMONAS, HOMOLOG OF; IFT121<br />
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KIAA1336
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</span>
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</h4>
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</div>
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<br />
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: WDR35</em></strong>
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</span>
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</p>
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<p>
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<strong>
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<em>
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Cytogenetic location: 2p24.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:19,910,263-19,990,105 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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2p24.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Cranioectodermal dysplasia 2
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</span>
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</td>
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<td>
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<span class="mim-font">
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613610
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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Short-rib thoracic dysplasia 7 with or without polydactyly
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</td>
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<td>
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<span class="mim-font">
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614091
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tbody>
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</table>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</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>WDR35 is a WD40 domain-containing protein. Studies in mouse and several lower organisms have implicated WDR35 in intraflagellar transport (summary by Gilissen et al. (2010)). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (2000) obtained a partial WDR35 clone, which they designated KIAA1336. RT-PCR ELISA detected highest expression in adult ovary, followed by testis, kidney, brain, and liver. Low expression was detected in fetal brain and adult heart and lung, with little to no expression in fetal liver and adult skeletal muscle, pancreas, and spleen. Moderate to high expression was detected in all adult brain regions examined. </p><p>Gilissen et al. (2010) determined that the 1,181-amino acid human WDR35 protein has 4 N-terminal WD40 motifs, a central WD40 motif, and a region of low complexity near the C terminus. They identified 3 additional WDR35 isoforms by database analysis. </p><p>By screening a rat brain/spinal cord expression cDNA library for proteins reactive against anti-shigatoxin antibody, Feng et al. (2010) cloned rat Wdr35, which they called Naofen. The deduced 1,170-amino acid protein contains 4 N-terminal WD40 domains and shares 92.7% identity with human WDR35. Quantitative RT-PCR detected Wdr35 expression in all rat tissues examined, with highest expression in testis, followed by brain, and lowest expression in spleen. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gilissen et al. (2010) determined that the WDR35 gene contains 28 coding exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Hartz (2010) mapped the WDR35 gene to chromosome 2p24.1 based on an alignment of the WDR35 sequence (GenBank AB037757) with the genomic sequence (GRCh37).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using small interfering RNA, Feng et al. (2010) showed that knockdown of Naofen in HEK293 cells reduced TNF-alpha (TNF; 191160)-induced caspase-3 (CASP3; 600636) activation and apoptosis. Overexpression of rat Naofen spontaneously induced caspase-3 activation and apoptosis and increased cell susceptibility to TNF-alpha-induced apoptosis. </p><p>By immunoblot and immunofluorescence analysis of Wdr35 -/- mouse fibroblasts, Caparros-Martin et al. (2015) observed no change in total protein levels of EVC (604831) and EVC2 (607261) in the mutant fibroblasts compared to controls; however, neither EVC or EVC2 was detected in Wdr35 -/- cilia. In response to the SMO agonist SAG, which drives SMO (SMOH; 601500) into the ciliary compartment, only Wdr35 -/- cilia remained negative for SMO immunofluorescence. The authors concluded that additional intraflagellar transport complex A (IFTA)-dependent functions requiring WDR35, but not retrograde transport, are specifically required for the correct ciliary entry of EVC, EVC2, and SMO. Levels of IFT43 (614068) appeared to depend on WDR35, since IFT43 was strongly reduced in Wdr35 -/- fibroblasts. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Cranioectodermal Dysplasia 2</em></strong></p><p>
|
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By exome sequencing, Gilissen et al. (2010) identified compound heterozygous mutations in the WDR35 gene (613602.0001-613602.0004) in 2 unrelated Dutch children with cranioectodermal dysplasia (CED2; 613610). Genetic analysis of 6 additional patients with a similar disorder and in 15 patients with Jeune syndrome (208500) did not yield any further WDR35 mutations. The authors noted that studies in Drosophila and C. elegans with WDR35 orthologs showed localization to the cilium and function in intraflagellar transport. Gilissen et al. (2010) postulated that the WDR35 mutations resulted in ciliary dysfunction due to disrupted intraflagellar transport. </p><p>In a 4-year-old Mexican boy with CED, Bacino et al. (2012) identified homozygosity for a missense mutation in the WDR35 gene (L520P; 613602.0008). </p><p>In an 8-month-old boy who had CED with multisutural craniosynostoses, Lin et al. (2013) identified compound heterozygosity for missense mutations in the WDR35 gene: H1031Y (613602.0009) and Y1068C (613602.0010). </p><p>In a 15-year-old Pakistani boy with relatively mild CED, Smith et al. (2016) identified homozygosity for a missense mutation in the WR35 gene (W1153C; 613602.0012). The authors noted that it was the most distal mutation yet reported. </p><p>In a 9-year-old Polish girl with Sensenbrenner syndrome, Walczak-Sztulpa et al. (2017) sequenced the candidate genes IFT122 (606145) and WDR35 and identified compound heterozygosity for mutations in the WDR35 gene: L641X (613602.0015) and D841V (613602.0016). The authors noted that this family exhibited intrafamilial variability, in that the proband's affected older sister had a more severe expression of the phenotype and had died in infancy. They suggested that the observed inter- and intrafamilial clinical variability within ciliopathies might be explained by 'mutational load,' including genetic heterogeneity, mutation type, genetic load, modifier effects, and/or oligogenic inheritance. </p><p><strong><em>Short-Rib Thoracic Dysplasia 7 with or without Polydactyly</em></strong></p><p>
|
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In 2 sibs with short-rib thoracic dysplasia-7 (SRTD7; 614091), Mill et al. (2011) identified a homozygous deletion mutation in the WDR35 gene (613602.0005). In an unrelated fetus with SRTD7, they identified compound heterozygous mutations in the WDR35 gene (613602.0006-613602.0007). All 3 patients exhibited polydactyly. </p><p>In 5 children from 3 unrelated families exhibiting a distinctive form of SRTD with overlapping features of both Ellis-van Creveld syndrome (see 225500) and cranioectodermal dysplasia, Caparros-Martin et al. (2015) identified biallelic mutations in the WDR35 gene (see, e.g., 613602.0011). All of the mutations were shown to affect splicing of WDR35. </p><p>In 3 sibs and an unrelated female infant with an unusual form of SRTD involving bent ribs and long bones as well as undermineralization of the skull, Duran et al. (2017) performed exome analysis and in both families identified compound heterozygosity for a missense mutation and a truncating mutation (see, e.g., 613602.0013 and 613602.0014). The sibs had polydactyly, whereas the unrelated female infant did not. </p><p>Toriyama et al. (2016) reported a male infant with SRTD and polydactyly due to apparent digenic inheritance; the infant exhibited double heterozygosity for a truncating mutation in the INTU gene (Q276X; 610621.0003) and a missense mutation in WDR35 (W311L; 613602.0013). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a mouse mutation screen for developmental phenotypes, Mill et al. (2011) identified a mutation in the Wdr35 gene as the cause of midgestation lethality, with abnormalities characteristic of defects in the Hedgehog signaling pathway. Mill et al. (2011) showed that endogenous WDR35 localizes to cilia and centrosomes throughout the developing embryo and that human and mouse fibroblasts lacking the protein fail to produce cilia. Through structural modeling, Mill et al. (2011) showed that WDR35 has strong homology to the COPI coatamers involved in vesicular trafficking and that human SRPS mutations affect key structural elements in WDR35. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>15 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 CRANIOECTODERMAL DYSPLASIA 2</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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WDR35, IVS2AS, A-G, -2
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<br />
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SNP: rs397515534,
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gnomAD: rs397515534,
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ClinVar: RCV000000037
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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 Dutch child with cranioectodermal dysplasia-2 (CED2; 613610), Gilissen et al. (2010) identified compound heterozygosity for 2 mutations in the WDR35 gene: an A-to-G transition in intron 2 (25-2A-G) resulting in a splice site mutation and premature termination, and a 1877A-G transition in exon 17 resulting in a glu626-to-gly (E626G; 613602.0002) substitution at a highly conserved residue. Neither mutation was found in 210 control alleles. The phenotype included short stature, dolichocephaly, craniosynostosis, narrow thorax with pectus excavatum, short limbs, and brachydactyly. Facial features included narrow palpebral fissures, telecanthus with hypertelorism, low-set simple ears, everted lower lip, and short neck. Teeth abnormalities included widely spaced, hypoplastic, and fused teeth. The boy also had joint laxity, inguinal hernia, and webbed fingers. There was no evidence of renal or hepatic disease, and he had normal intelligence. </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 CRANIOECTODERMAL DYSPLASIA 2</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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WDR35, GLU626GLY
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<br />
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SNP: rs267607174,
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ClinVar: RCV000000038
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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 glu626-to-gly (E626G) mutation in the WDR35 gene that was found in compound heterozygous state in a patient with cranioectodermal dysplasia-2 (CED2; 613610) by Gilissen et al. (2010), see 613602.0001. </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 CRANIOECTODERMAL DYSPLASIA 2</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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WDR35, 1-BP DEL, 2891C
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<br />
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SNP: rs397515334,
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gnomAD: rs397515334,
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ClinVar: RCV000000039, RCV005024976
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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 Dutch child with cranioectodermal dysplasia-2 (CED2; 613610), Gilissen et al. (2010) identified compound heterozygosity for 2 mutations in the WDR35 gene: a 1-bp deletion (2891delC) in exon 25 resulting in a frameshift and premature termination, and a 2623G-A transition in exon 23 resulting in an ala875-to-thr (A875T; 613602.0004) substitution at a highly conserved region. Neither mutation was found in 210 control alleles. The phenotype included short stature, dolichocephaly, craniosynostosis, narrow thorax with pectus excavatum, short limbs, and brachydactyly. Facial features included narrow palpebral fissures, telecanthus with hypertelorism, low-set simple ears, everted lower lip, and short neck. Teeth abnormalities included widely spaced, hypoplastic, and fused teeth. The boy also had joint laxity, inguinal hernia, and webbed fingers. There was no evidence of renal or hepatic disease, and he had normal intelligence. </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 CRANIOECTODERMAL DYSPLASIA 2</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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WDR35, ALA875THR
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<br />
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SNP: rs267607175,
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gnomAD: rs267607175,
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ClinVar: RCV000000040, RCV000508347
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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 ala875-to-thr (A875T) mutation in the WDR35 gene that was found in compound heterozygous state in a patient with cranioectodermal dysplasia-2 (CED2; 613610) by Gilissen et al. (2010), see 613602.0003. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0005 SHORT-RIB THORACIC DYSPLASIA 7 WITH POLYDACTYLY</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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WDR35, 2,847-BP DEL
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<br />
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ClinVar: RCV000024037
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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 with short-rib thoracic dysplasia-7 with polydactyly (SRTD7; 614091), who were originally reported by Kannu et al. (2007), Mill et al. (2011) identified an in-frame homozygous 2,847-bp deletion spanning exon 5 of the WDR35 gene. Both parents and an unaffected sib were heterozygous for the deletion. </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>.0006 SHORT-RIB THORACIC DYSPLASIA 7 WITH POLYDACTYLY</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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WDR35, ARG545TER
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<br />
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SNP: rs387907085,
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gnomAD: rs387907085,
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ClinVar: RCV000024038
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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 fetus with short-rib thoracic dysplasia-7 with polydactyly (SRTD7; 614091), Mill et al. (2011) identified compound heterozygosity for 2 mutations in the WDR35 gene: a 1633C-T transition resulting in an arg545-to-ter (R545X) substitution, and a 781T-C transition resulting in a trp261-to-arg (W261R) substitution (613602.0007). The nonsense mutation was inherited from the mother and the missense mutation from the father. </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>.0007 SHORT-RIB THORACIC DYSPLASIA 7 WITH POLYDACTYLY</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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|
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<div>
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<span class="mim-text-font">
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WDR35, TRP261ARG
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<br />
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|
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SNP: rs431905505,
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gnomAD: rs431905505,
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|
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ClinVar: RCV000024039
|
|
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|
|
</span>
|
|
</div>
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<div>
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|
<span class="mim-text-font">
|
|
<p>For discussion of the trp261-to-arg (W261R) mutation that was found in compound heterozygous state in a fetus with short-rib thoracic dysplasia-7 (SRTD7; 614091) by Mill et al. (2011), see 613602.0006. </p>
|
|
</span>
|
|
</div>
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|
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|
|
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CRANIOECTODERMAL DYSPLASIA 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
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|
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|
WDR35, LEU520PRO
|
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<br />
|
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|
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SNP: rs397515533,
|
|
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|
|
ClinVar: RCV000055831
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old Mexican boy with cranioectodermal dysplasia-2 (CED2; 613610), Bacino et al. (2012) identified homozygosity for an A-to-G transition (chr2.20,146,297A-G, GRCh37) in exon 16 of the WDR35 gene, resulting in a leu520-to-pro (L520P) substitution at a highly conserved residue. The unaffected parents and 2 unaffected sibs were heterozygous for the mutation, which was not found in the 1000 Genomes Project, NHLBI Exome Sequencing Project, or NIEHS EGP databases. DNA was unavailable from 3 more affected sibs in the family, including 2 who died at 9 months and 13 months of age, and an affected fetus terminated at 21 weeks' gestation. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CRANIOECTODERMAL DYSPLASIA 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
WDR35, HIS1031TYR
|
|
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|
|
<br />
|
|
|
|
SNP: rs1553316264,
|
|
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|
|
|
|
|
ClinVar: RCV000578480
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 8-month-old boy with cranioectodermal dysplasia-2 (CED2; 613610), who had a 'cloverleaf' skull due to multiple suture synostoses, Lin et al. (2013) identified compound heterozygosity for a c.3091C-T transition (c.3091C-T, NM_001006657) in exon 26 of the WDR35 gene, resulting in a his1031-to-tyr (H1031Y) substitution, and a c.3203A-G transition in exon 27, resulting in a tyr1068-to-cys (Y1068C; 613602.0010) substitution. His unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in public variant databases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CRANIOECTODERMAL DYSPLASIA 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WDR35, TYR1068CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs541910371,
|
|
|
|
|
|
gnomAD: rs541910371,
|
|
|
|
|
|
ClinVar: RCV000507380, RCV000578488, RCV001266500, RCV005027590
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.3203A-G transition (c.3203A-G, NM_001006657) in exon 27 of the WDR35 gene, resulting in a tyr1068-to-cys (Y2068C) substitution, that was found in compound heterozygous state in an 8-month-old boy with cranioectodermal dysplasia-2 (CED2; 613610) by Lin et al. (2013), see 613602.0009. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 SHORT-RIB THORACIC DYSPLASIA 7 WITH POLYDACTYLY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WDR35, IVS2AS, T-A, -18
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1553324519,
|
|
|
|
|
|
|
|
ClinVar: RCV000578492
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected brothers with short-rib thoracic dysplasia and polydactyly (SRTD7; 614091), born of first-cousin parents from Reunion Island, Caparros-Martin et al. (2015) identified homozygosity for a splice site mutation (c.143-18T-A, NM_001006657.1) in intron 2 of the WDR35 gene. The brothers died of cardiorespiratory failure at ages 5 months and 13 months. Their unaffected parents were heterozygous for the mutation, which was not found in an unaffected brother or in the 1000 Genomes Project, NHLBI Exome Variant Server, or ExAC databases. RT-PCR of peripheral blood RNA from the parents revealed a small cDNA fragment that corresponded to skipping of exon 3, and analysis of transfected COS-7 cells confirmed no inclusion of exon 3 in amplified products. Experiments in transfected COS-7 cells using minigene constructs suggested that the mutation generates an intronic splicing silencer. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 CRANIOECTODERMAL DYSPLASIA 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WDR35, TRP1153CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1553313859,
|
|
|
|
|
|
|
|
ClinVar: RCV000578479
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old boy with cranioectodermal dysplasia-2 (CED2; 613610), born of fourth-cousin Pakistani parents, Smith et al. (2016) identified homozygosity for a c.3459G-T transversion (c.3459G-T, NM_0010066575.1) in exon 28 of the WDR35 gene, resulting in a trp1153-to-cys (W1153C) substitution at a highly conserved residue. The mutation was not found in the dbSNP, Exome Variant Server, or ExAC databases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 SHORT-RIB THORACIC DYSPLASIA 7 WITHOUT POLYDACTYLY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SHORT-RIB THORACIC DYSPLASIA 7/20 WITH POLYDACTYLY, DIGENIC, INCLUDED (1 patient)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WDR35, TRP311LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs200649783,
|
|
|
|
|
|
gnomAD: rs200649783,
|
|
|
|
|
|
ClinVar: RCV000516065, RCV000578486, RCV000608080, RCV000755748, RCV000851218, RCV001353118, RCV001764511
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a female infant (R10-483A) with short-rib thoracic dysplasia (SRTD7; 614091), who did not exhibit polydactyly and died at 1 week of life, Duran et al. (2017) identified compound heterozygosity for a c.932G-T transversion in the WDR35 gene, resulting in a trp311-to-leu (W311L) substitution, and a 1-bp deletion (c.1501delC; 613602.0014), predicted to result in a premature termination codon (Gly501LysfsTer10). Analysis of cultured patient chondrocytes showed decreased IFT43 (614068) levels. In addition, there was a reduction in the percentage of cilia present on patient chondrocytes compared to controls, and the mutant cilia showed reduced lengths and were abnormally shaped. </p><p>In a male infant (R04-176A) with SRTD and polydactyly, Toriyama et al. (2016) identified double heterozygosity for the W311L mutation in the WDR35 gene and a truncating mutation in the INTU gene (Q276X; 610621.0003). The patient died in the neonatal period. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 SHORT-RIB THORACIC DYSPLASIA 7 WITHOUT POLYDACTYLY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WDR35, 1-BP DEL, 1501C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886044119,
|
|
|
|
|
|
gnomAD: rs886044119,
|
|
|
|
|
|
ClinVar: RCV000323877, RCV000578495, RCV000851219, RCV002518074
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion (c.1501delC) in the WDR35 gene, resulting in a premature termination codon (Gln501LysfsTer10), that was found in compound heterozygous state in an infant with short-rib thoracic dysplasia (SRTD7; 614091) by Duran et al. (2017), see 613602.0013. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 CRANIOECTODERMAL DYSPLASIA 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WDR35, LEU641TER ({dbSNP rs199952377})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs199952377,
|
|
|
|
|
|
gnomAD: rs199952377,
|
|
|
|
|
|
ClinVar: RCV000055830, RCV000288028, RCV000515864, RCV000648351, RCV000826131, RCV001557398
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old Polish girl with Sensenbrenner syndrome (CED2; 613610), Walczak-Sztulpa et al. (2017) identified compound heterozygosity for mutations in the WDR35 gene: a c.1922T-G transversion in exon 18, resulting in a leu641-to-ter (L641X) substitution, and a c.2522A-T transversion in exon 22, resulting in an asp841-to-val (D841V; 613602.0016) substitution. Her unaffected parents were each heterozygous for 1 of the mutations; DNA was unavailable from her affected older sister, who had died in infancy from respiratory, hepatic, and renal insufficiency. The authors noted that the nonsense mutation (L641X) had previously been reported in 2 patients with Sensenbrenner syndrome (Hoffer et al., 2013; Li et al., 2015) and was present in the ExAC and UCSC Genome Browser databases at an allele frequency of 0.018% and 0.15%, respectively. The missense mutation (D841V) is located at a highly conserved residue and was not found in the 1000 Genomes Project, NHLBI Exome Variant Server, or ExAC databases. </p>
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Walczak-Sztulpa, J., Wawrocka, A., Sobierajewicz, A., Kuszel, L., Zawadzki, J., Grenda, R., Swiader-Lesniak, A., Kocyla-Karczmarewicz, B., Wnuk, A., Latos-Bielenska, A., Chrzanowska, K. H.
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