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Entry
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- *609883 - MKS TRANSITION ZONE COMPLEX SUBUNIT 1; MKS1
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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">*609883</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<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="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#evolution">Evolution</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li 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/609883">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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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000011143;t=ENST00000393119" 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=54903" 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=609883" 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="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000011143;t=ENST00000393119" 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_001321268,NM_001321269,NM_001330397,NM_001411113,NM_017777,XM_005257485,XM_011524957,XM_011524958,XM_011524960,XM_047436333,XM_047436334,XM_047436335" 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_017777" 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=609883" 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=07900&isoform_id=07900_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/MKS1" 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/7020381,14603201,48146575,74027166,89242137,92087008,119614882,119614883,119614884,194375049,260064077,530412471,767995164,767995166,767995171,957951193,957951196,957951199,1007892856,1007892858,1060099050,2217312645,2217312647,2217312649,2288627406,2462556216,2462556218,2462556220,2462556222,2462556224,2462556226,2462556228" 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/Q9NXB0" 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=54903" 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=ENSG00000011143;t=ENST00000393119" 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=MKS1" 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=MKS1" 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+54903" 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/MKS1" 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:54903" 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/54903" 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=chr17&hgg_gene=ENST00000393119.7&hgg_start=58205441&hgg_end=58219255&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:7121" 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:7121" 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=609883[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=609883[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/MKS1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000011143" 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=MKS1" 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=MKS1" 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=MKS1" 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=MKS1&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/PA30840" 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:7121" 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/FBgn0030395.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:3584243" 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/MKS1#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:3584243" 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/54903/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=54903" 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=WBGene00020100;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-030131-3813" 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">
|
|
<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=MKS1&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>
|
|
609883
|
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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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MKS TRANSITION ZONE COMPLEX SUBUNIT 1; MKS1
|
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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">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MKS1 GENE<br />
|
|
BBS13 GENE; BBS13<br />
|
|
FLJ20345
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MKS1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MKS1</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/17/781?start=-3&limit=10&highlight=781">17q22</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:58205441-58219255&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'})">17:58,205,441-58,219,255</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=615990,617121,249000" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/781?start=-3&limit=10&highlight=781">
|
|
17q22
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Bardet-Biedl syndrome 13
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/615990"> 615990 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
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|
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|
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|
|
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</tr>
|
|
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|
|
|
|
|
|
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|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Joubert syndrome 28
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617121"> 617121 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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<p>MKS1 belongs to a small family of B9 domain-containing proteins that also includes B9D1 (<a href="/entry/614144">614144</a>) and B9D2 (<a href="/entry/611951">611951</a>), and all 3 B9 domain-containing proteins associate with basal bodies and primary cilia in mammalian cells (summary by <a href="#2" class="mim-tip-reference" title="Bialas, N. J., Inglis, P. N., Li, C., Robinson, J. F., Parker, J. D. K., Healey, M. P., Davis, E. E., Inglis, C. D., Toivonen, T., Cottell, D. C., Blacque, O. E., Quarmby, L. M., Katsanis, N., Leroux, M. R. <strong>Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins.</strong> J. Cell Sci. 122: 611-624, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208769</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208769[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/10.1242/jcs.028621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208769">Bialas et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19208769" 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="#7" class="mim-tip-reference" title="Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M. <strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong> Nature Genet. 38: 155-157, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415886</a>] [<a href="https://doi.org/10.1038/ng1714" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415886">Kyttala et al. (2006)</a> identified the MKS1 gene (FLJ20345) in a 100-kb region of chromosome 17q23 to which Meckel syndrome had been linked in Finnish families. The gene contains an open reading frame (bp 76-1755) coding for a 559-amino acid polypeptide containing a conserved B9 domain. Comparison of sequence across human, mouse, zebrafish, fruit fly, and C. elegans showed high conservation. Human and mouse coding regions are 86 to 88% similar at the nucleotide level and 89% at the amino acid level. In situ hybridization analyses showed a relatively broad tissue expression of Mks1 in mouse embryo at embryonic day 15.5. The expression was especially prominent in tissues showing malformations characteristic of Meckel syndrome: brain, liver, kidney, and digits of the upper limbs. Highest expression was observed in bronchiolar epithelium. Hypoplastic lungs are frequently reported in MKS patients, but this feature had been presumed to be caused by lack of amniotic fluid and mechanical pressure from the enlarged kidneys. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415886" 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 immunohistochemical analysis of 18- to 20-week-old human fetal kidneys, <a href="#5" class="mim-tip-reference" title="Dawe, H. R., Smith, U. M., Cullinane, A. R., Gerrelli, D., Cox, P., Badano, J. L., Blair-Reid, S., Sriram, N., Katsanis, N., Attie-Bitach, T., Afford, S. C., Copp, A. J., Kelly, D. A., Gull, K., Johnson, C. A. <strong>The Meckel-Gruber syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.</strong> Hum. Molec. Genet. 16: 173-186, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17185389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17185389</a>] [<a href="https://doi.org/10.1093/hmg/ddl459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17185389">Dawe et al. (2007)</a> found moderate to high expression of meckelin (MKS3, or TMEM67; <a href="/entry/609884">609884</a>) and MKS1 at the proximal renal tubule epithelia, but not at glomeruli. In liver, these proteins were expressed at the biliary epithelium of larger bile ducts, but not in hepatocytes. In biliary epithelial cells, MKS1 showed a clear punctate doublet staining pattern characteristic of a centrosomal localization. In HEK293 cells, MKS1 showed a broad intracellular localization with occasional distribution at the cell border. Western blot analysis detected MKS1 at an apparent molecular mass of 70 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17185389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using RNA interference, <a href="#5" class="mim-tip-reference" title="Dawe, H. R., Smith, U. M., Cullinane, A. R., Gerrelli, D., Cox, P., Badano, J. L., Blair-Reid, S., Sriram, N., Katsanis, N., Attie-Bitach, T., Afford, S. C., Copp, A. J., Kelly, D. A., Gull, K., Johnson, C. A. <strong>The Meckel-Gruber syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.</strong> Hum. Molec. Genet. 16: 173-186, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17185389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17185389</a>] [<a href="https://doi.org/10.1093/hmg/ddl459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17185389">Dawe et al. (2007)</a> found that knockdown of either Mks1 or Mks3 in mouse inner medullary IMCD-3 cells blocked centriole migration to the apical membrane and formation of the primary cilium. Coimmunoprecipitation experiments showed that wildtype Mks1 and Mks3 interacted, and knockdown of either Mks1 or Mks3 in IMCD-3 cells decreased the formation of highly branched structures and tubules in 3-dimensional cultures. <a href="#5" class="mim-tip-reference" title="Dawe, H. R., Smith, U. M., Cullinane, A. R., Gerrelli, D., Cox, P., Badano, J. L., Blair-Reid, S., Sriram, N., Katsanis, N., Attie-Bitach, T., Afford, S. C., Copp, A. J., Kelly, D. A., Gull, K., Johnson, C. A. <strong>The Meckel-Gruber syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.</strong> Hum. Molec. Genet. 16: 173-186, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17185389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17185389</a>] [<a href="https://doi.org/10.1093/hmg/ddl459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17185389">Dawe et al. (2007)</a> concluded that MKS1 and MKS3 have roles in ciliogenesis and renal tubulogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17185389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Tammachote, R., Hommerding, C. J., Sinders, R. M., Miller, C. A., Czarnecki, P. G., Leightner, A. C., Salisbury, J. L., Ward, C. J., Torres, V. E., Gattone, V. H., II, Harris, P. C. <strong>Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3.</strong> Hum. Molec. Genet. 18: 3311-3323, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19515853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19515853</a>] [<a href="https://doi.org/10.1093/hmg/ddp272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19515853">Tammachote et al. (2009)</a> showed that kidney tissue and cells from MKS1 and MKS3 (<a href="/entry/607361">607361</a>) patients showed defects in centrosome and cilia number, including multiciliated respiratory-like epithelia, and longer cilia. Stable shRNA knockdown of Mks1 and Mks3 in IMCD-3 cells induced multiciliated and multicentrosomal phenotypes. MKS1 and MKS3 functions are required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. <a href="#11" class="mim-tip-reference" title="Tammachote, R., Hommerding, C. J., Sinders, R. M., Miller, C. A., Czarnecki, P. G., Leightner, A. C., Salisbury, J. L., Ward, C. J., Torres, V. E., Gattone, V. H., II, Harris, P. C. <strong>Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3.</strong> Hum. Molec. Genet. 18: 3311-3323, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19515853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19515853</a>] [<a href="https://doi.org/10.1093/hmg/ddp272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19515853">Tammachote et al. (2009)</a> concluded that MKS1 and MKS3 are ciliopathies, with new cilia-related eye and sperm phenotypes defined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19515853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Williams, C. L., Li, C., Kida, K., Inglis, P. N., Mohan, S., Semenec, L., Bialas, N. J., Stupay, R. M., Chen, N., Blacque, O. E., Yoder, B. K., Leroux, M. R. <strong>MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.</strong> J. Cell. Biol. 192: 1023-1041, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21422230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21422230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21422230[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/10.1083/jcb.201012116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21422230">Williams et al. (2011)</a> showed that the conserved proteins Mks1, Mksr1 (B9D1), Mksr2 (B9D2; <a href="/entry/611951">611951</a>), Tmem67, Rpgrip1l (<a href="/entry/610937">610937</a>), Cc2d2a (<a href="/entry/612013">612013</a>), Nphp1 (<a href="/entry/607100">607100</a>), and Nphp4 (<a href="/entry/607215">607215</a>) functioned at an early stage of ciliogenesis in C. elegans. These 8 proteins localized to the ciliary transition zone and established attachments between the basal body and transition zone membrane. They also provided a docking site that restricted vesicle fusion to vesicles containing ciliary proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21422230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using tandem affinity purification and mass spectrometry to isolate proteins that purified with B9d1 (<a href="/entry/614144">614144</a>) in mouse IMCD3 cells and embryonic fibroblasts, <a href="#3" class="mim-tip-reference" title="Chih, B., Liu, P., Chinn, Y., Chalouni, C., Komuves, L. G., Hass, P. E., Sandoval, W., Peterson, A. S. <strong>A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain.</strong> Nature Cell Biol. 14: 61-72, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22179047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22179047</a>] [<a href="https://doi.org/10.1038/ncb2410" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22179047">Chih et al. (2012)</a> identified several components of the B9d1-containing ciliary complex, including Tmem231 (<a href="/entry/614949">614949</a>), Tmem17 (<a href="/entry/614950">614950</a>), B9d2 (<a href="/entry/611951">611951</a>), Tctn1 (<a href="/entry/609863">609863</a>), Tctn2 (<a href="/entry/613846">613846</a>), Mks1, Ahi1 (<a href="/entry/608894">608894</a>), Cc2d2a (<a href="/entry/612013">612013</a>), and Kctd10 (<a href="/entry/613421">613421</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22179047" 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="#7" class="mim-tip-reference" title="Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M. <strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong> Nature Genet. 38: 155-157, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415886</a>] [<a href="https://doi.org/10.1038/ng1714" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415886">Kyttala et al. (2006)</a> determined that the 14-kb MKS1 gene contains 18 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415886" 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="#7" class="mim-tip-reference" title="Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M. <strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong> Nature Genet. 38: 155-157, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415886</a>] [<a href="https://doi.org/10.1038/ng1714" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415886">Kyttala et al. (2006)</a> stated that the FLJ20345 gene (MKS1 gene) is on chromosome 17q23. The mouse homolog maps to a region of chromosome 11 demonstrating homology of synteny with human 17q23. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 2/19/2015."None>Gross (2015)</a> mapped the MKS1 gene to chromosome 17q22 based on an alignment of the MKS1 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC010061" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC010061</a>) with the genomic sequence (GRCh38).</p>
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<p>Using database analysis, <a href="#2" class="mim-tip-reference" title="Bialas, N. J., Inglis, P. N., Li, C., Robinson, J. F., Parker, J. D. K., Healey, M. P., Davis, E. E., Inglis, C. D., Toivonen, T., Cottell, D. C., Blacque, O. E., Quarmby, L. M., Katsanis, N., Leroux, M. R. <strong>Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins.</strong> J. Cell Sci. 122: 611-624, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208769</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208769[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/10.1242/jcs.028621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208769">Bialas et al. (2009)</a> found orthologs of B9D1, B9D2, and MKS1 in the vast majority of ciliated species, but not in nonciliated organisms. The 3 B9 domain-containing proteins appeared to be evolutionarily ancient, and the duplications resulting in the 3 protein clades preceded speciation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19208769" 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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Meckel syndrome (MKS) is a severe autosomal recessive fetal developmental disorder. The clinical hallmarks are occipital meningoencephalocele, cystic kidney dysplasia, fibrotic changes of the liver, and polydactyly. Genetic heterogeneity was established by genome linkage scans. The MKS1 locus on 17q (<a href="/entry/249000">249000</a>) was identified in Finnish families. <a href="#7" class="mim-tip-reference" title="Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M. <strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong> Nature Genet. 38: 155-157, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415886</a>] [<a href="https://doi.org/10.1038/ng1714" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415886">Kyttala et al. (2006)</a> found that in Finnish families in which the MKS1 locus was identified, 70% of the patients were homozygous for the same haplotype on 17q23. Sequence analysis of the MKS1 gene showed a 29-bp deletion in intron 15 (<a href="#0001">609883.0001</a>) in 3 Finnish families sharing the MKS1 haplotype and in 1 German patient with evidence of linkage to 17q23. This deletion was located only 4 bp away from the splice acceptor site and was predicted to interrupt the splice branching site. The intronic deletion was detected as a size difference in PCR products from genomic DNA, and analysis of DNA samples of 26 Finnish families with the common founder haplotype confirmed that all individuals were homozygous, and that parents were heterozygous, for this deletion. Comparative genomics and proteomics data implicated MKS1 in ciliary function. Review of the series of 67 Finnish MKS patients reported by <a href="#10" class="mim-tip-reference" title="Salonen, R. <strong>The Meckel syndrome: clinicopathological findings in 67 patients.</strong> Am. J. Med. Genet. 18: 671-689, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6486167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6486167</a>] [<a href="https://doi.org/10.1002/ajmg.1320180414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6486167">Salonen (1984)</a> showed 3 cases with situs inversus totalis (see <a href="/entry/270100">270100</a>), which implied an increased risk for this rare condition in Meckel syndrome and would provide another link to ciliary dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6486167+16415886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Consugar, M. B., Kubly, V. J., Lager, D. J., Hommerding, C. J., Wong, W. C., Bakker, E., Gattone, V. H., II, Torres, V. E., Breuning, M. H., Harris, P. C. <strong>Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3.</strong> Hum. Genet. 121: 591-599, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17377820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17377820</a>] [<a href="https://doi.org/10.1007/s00439-007-0341-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17377820">Consugar et al. (2007)</a> identified mutations in the MKS1 gene in affected individuals in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All 5 families had the major Finnish deletion mutation: 2 were homozygous, and 3 were compound heterozygous with another pathogenic mutation (<a href="#0004">609883.0004</a> and <a href="#0005">609883.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17377820" 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>Bardet-Biedl Syndrome 13</em></strong></p><p>
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<a href="#8" class="mim-tip-reference" title="Leitch, C. C., Zaghloul, N. A., Davis, E. E., Stoetzel, C., Diaz-Font, A., Rix, S., Alfadhel, M., Lewis, R. A., Eyaid, W., Banin, E., Dollfus, H., Beales, P. L., Badano, J. L., Katsanis, N. <strong>Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome.</strong> Nature Genet. 40: 443-448, 2008. Note: Erratum: Nature Genet. 40: 927 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327255</a>] [<a href="https://doi.org/10.1038/ng.97" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18327255">Leitch et al. (2008)</a> demonstrated that mutations in MKS1, MKS3 (<a href="/entry/609884">609884</a>), and CEP290 (<a href="/entry/610142">610142</a>) either can cause Bardet-Biedl syndrome (see <a href="/entry/209900">209900</a>) or may have a potential epistatic effect on mutations in known BBS-associated loci. Five of 6 families with both MKS1 and BBS mutations manifested seizures, a feature that is not a typical component of either Meckel or Bardet-Biedl syndrome. Functional studies in zebrafish showed that mks1 is necessary for gastrulation movements and that it interacts genetically with known bbs genes. In 1 patient compound heterozygous mutations in MKS1 resulting in the BBS phenotype were found (see <a href="#0006">609883.0006</a>). In 5 families a single heterozygous mutation in MKS1 was found. Two of these families also carried mutations in BBS10 (<a href="/entry/610148">610148</a>), and a third family carried a homozygous mutation in BBS1 (<a href="/entry/209901">209901</a>). <a href="#8" class="mim-tip-reference" title="Leitch, C. C., Zaghloul, N. A., Davis, E. E., Stoetzel, C., Diaz-Font, A., Rix, S., Alfadhel, M., Lewis, R. A., Eyaid, W., Banin, E., Dollfus, H., Beales, P. L., Badano, J. L., Katsanis, N. <strong>Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome.</strong> Nature Genet. 40: 443-448, 2008. Note: Erratum: Nature Genet. 40: 927 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327255</a>] [<a href="https://doi.org/10.1038/ng.97" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18327255">Leitch et al. (2008)</a> concluded that their data extended the genetic stratification of ciliopathies and suggested that BBS and MKS, although distinct clinically, are allelic forms of the same molecular spectrum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18327255" 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 Chinese boy with BBS13, <a href="#14" class="mim-tip-reference" title="Xing, D.-J., Zhang, H.-X., Huang, N., Wu, K.-C., Huang, X.-F., Huang, F., Tong, Y., Pang, C.-P., Qu, J., Jin, Z.-B. <strong>Comprehensive molecular diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing.</strong> PLoS One 9: e90599, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24608809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24608809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24608809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pone.0090599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24608809">Xing et al. (2014)</a> identified compound heterozygous missense mutations in the MKS1 gene (Y461C; <a href="#0008">609883.0008</a>) and R534Q (<a href="#0009">609883.0009</a>). The mutations were identified by high-throughput targeted exome sequencing of 144 known genes responsible for inherited retinal diseases. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24608809" 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>Joubert Syndrome 28</em></strong></p><p>
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In 2 unrelated patients with Joubert syndrome-28 (JBTS28; <a href="/entry/617121">617121</a>), <a href="#9" class="mim-tip-reference" title="Romani, M., Micalizzi, A., Kraoua, I., Dotti, M. T., Cavallin, M., Sztriha, L., Ruta, R., Mancini, F., Mazza, T., Castellana, S., Hanene, B., Carlucio, M. A., Darra, F., Mate, A., Zimmermann, A., Gouider-Khouja, N., Valente, E. M. <strong>Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome.</strong> Orphanet J. Rare Dis. 9: 72, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24886560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24886560</a>] [<a href="https://doi.org/10.1186/1750-1172-9-72" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24886560">Romani et al. (2014)</a> identified biallelic mutations in the MKS1 gene (<a href="#0010">609883.0010</a>-<a href="#0012">609883.0012</a>). Functional studies of the variants and studies of patient cells were not performed. The patients were part of a group of 260 JBTS patients who were screened for mutations in ciliopathy genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24886560" 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="#12" class="mim-tip-reference" title="Weatherbee, S. D., Niswander, L. A., Anderson, K. V. <strong>A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and hedgehog signaling.</strong> Hum. Molec. Genet. 18: 4565-4575, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19776033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19776033</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19776033[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/10.1093/hmg/ddp422" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19776033">Weatherbee et al. (2009)</a> showed that loss of function of mouse Mks1 resulted in an accurate model of Meckel syndrome, with structural abnormalities in the neural tube, biliary duct, limb patterning, bone development, and the kidney. In contrast to cell culture studies, loss of Mks1 in vivo did not interfere with apical localization of epithelial basal bodies, but rather led to defective cilia formation in most, but not all, tissues. Analysis of patterning in the neural tube and the limb demonstrated altered Hedgehog (Hh) pathway signaling underlying some MKS defects, although both tissues showed an expansion of the domain of response to Shh (<a href="/entry/600725">600725</a>) signaling, unlike the phenotypes seen in other mutants with cilia loss. Other defects in the skull, lung, rib cage, and long bones were thought likely to be the result of disruption of Hh signaling. <a href="#12" class="mim-tip-reference" title="Weatherbee, S. D., Niswander, L. A., Anderson, K. V. <strong>A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and hedgehog signaling.</strong> Hum. Molec. Genet. 18: 4565-4575, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19776033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19776033</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19776033[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/10.1093/hmg/ddp422" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19776033">Weatherbee et al. (2009)</a> concluded that disruption of Hh signaling may explain many, but not all, of the defects caused by loss of Mks1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19776033" 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="#2" class="mim-tip-reference" title="Bialas, N. J., Inglis, P. N., Li, C., Robinson, J. F., Parker, J. D. K., Healey, M. P., Davis, E. E., Inglis, C. D., Toivonen, T., Cottell, D. C., Blacque, O. E., Quarmby, L. M., Katsanis, N., Leroux, M. R. <strong>Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins.</strong> J. Cell Sci. 122: 611-624, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208769</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208769[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/10.1242/jcs.028621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208769">Bialas et al. (2009)</a> disrupted the B9 domains of C. elegans mks1, mksr1, and mksr2. In contrast to the defect found in mouse cells, C. elegans expressing single, double, or triple mks/mksr mutants showed no overt defects in ciliary structure, nor in intraflagellar transport, chemosensation, osmosensation, or lipid accumulation. However, disruption of one B9 domain-containing protein resulted in mislocalization of the others, and all possible double mks/mksr mutant combinations altered insulin signaling, leading to increased life span. The mks1/mksr1/mksr2 triple mutant did not exhibit a longevity phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19208769" 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">rs386834043 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs386834043;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=rs386834043" 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=rs386834043" 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=RCV000168467 OR RCV000210823 OR RCV000273342 OR RCV000491550 OR RCV000984005 OR RCV002515190 OR RCV003474892 OR RCV004528921 OR RCV005016510" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000168467, RCV000210823, RCV000273342, RCV000491550, RCV000984005, RCV002515190, RCV003474892, RCV004528921, RCV005016510" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000168467...</a>
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<p>In 3 Finnish families sharing the founder MKS1 haplotype and in 1 German patient with evidence of linkage of Meckel syndrome to 17q23 (MKS1; <a href="/entry/249000">249000</a>), <a href="#7" class="mim-tip-reference" title="Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M. <strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong> Nature Genet. 38: 155-157, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415886</a>] [<a href="https://doi.org/10.1038/ng1714" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415886">Kyttala et al. (2006)</a> found that the MKS1 gene showed a 29-bp deletion in intron 15 as the cause of the anomaly. This deletion was located only 4 bp away from the splice acceptor site and probably interrupted the splice branching site. The same intronic deletion was found in 26 Finnish families with a common founder haplotype; all affected individuals were homozygous, and the parents heterozygous, for the deletion, which <a href="#7" class="mim-tip-reference" title="Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M. <strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong> Nature Genet. 38: 155-157, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415886</a>] [<a href="https://doi.org/10.1038/ng1714" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415886">Kyttala et al. (2006)</a> called the MKS1-Fin(major) mutation. This mutation was also found in an American family and in a family of mixed Swedish-Portuguese-Irish descent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415886" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Auber, B., Burfeind, P., Herold, S., Schoner, K., Simson, G., Rauskolb, R., Rehder, H. <strong>A disease causing deletion of 29 base pairs in intron 15 in the MKS1 gene is highly associated with the campomelic variant of the Meckel-Gruber syndrome.</strong> Clin. Genet. 72: 454-459, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935508</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00880.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17935508">Auber et al. (2007)</a> identified the 29-bp deletion in intron 15 of the MKS1 gene in 8 of 20 unrelated fetuses diagnosed clinically with MKS. Six cases, consisting of 1 heterozygous and 5 homozygous mutations, had the campomelic variant of the disorder. The carrier frequency of this mutation in the German population was determined to be 1 in 260. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17935508" 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">rs730880323 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs730880323;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=rs730880323" 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=rs730880323" 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=RCV000022412" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022412" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022412</a>
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<p>In a case of Meckel syndrome (MKS1; <a href="/entry/249000">249000</a>) of German ancestry, <a href="#7" class="mim-tip-reference" title="Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M. <strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong> Nature Genet. 38: 155-157, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415886</a>] [<a href="https://doi.org/10.1038/ng1714" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415886">Kyttala et al. (2006)</a> found compound heterozygosity for mutations in MKS1 located at the very beginning of the transcript: a 5-bp insertion in exon 1 (50insCCGGG), causing a frameshift (Pro17fsTer163); and a T-to-C substitution at the splice donor site of intron 1 (IVS1+2T-C; <a href="#0003">609883.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415886" 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">rs386834052 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs386834052;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=rs386834052" 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=rs386834052" 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=RCV000022413 OR RCV000665702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022413, RCV000665702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022413...</a>
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<p>For discussion of the splice site mutation in intron 1 of the MKS1 gene (IVS1+2T-C) that was found in compound heterozygous state in a patient with Meckel syndrome (MKS1; <a href="/entry/249000">249000</a>) by <a href="#7" class="mim-tip-reference" title="Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M. <strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong> Nature Genet. 38: 155-157, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415886</a>] [<a href="https://doi.org/10.1038/ng1714" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16415886">Kyttala et al. (2006)</a>, see <a href="#0002">609883.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415886" 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> rs199874059 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199874059;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/rs199874059?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=rs199874059" 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=rs199874059" 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=RCV000022414 OR RCV000668139 OR RCV001038005 OR RCV001570919 OR RCV003472957 OR RCV004732522" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022414, RCV000668139, RCV001038005, RCV001570919, RCV003472957, RCV004732522" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022414...</a>
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<p>In a 16-week-old fetus with Meckel syndrome (MKS1; <a href="/entry/249000">249000</a>) diagnosed by ultrasound, <a href="#4" class="mim-tip-reference" title="Consugar, M. B., Kubly, V. J., Lager, D. J., Hommerding, C. J., Wong, W. C., Bakker, E., Gattone, V. H., II, Torres, V. E., Breuning, M. H., Harris, P. C. <strong>Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3.</strong> Hum. Genet. 121: 591-599, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17377820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17377820</a>] [<a href="https://doi.org/10.1007/s00439-007-0341-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17377820">Consugar et al. (2007)</a> identified compound heterozygosity for 2 mutations in the MKS1 gene: a G-to-A transition in intron 11 (IVS11+1G-A), resulting in a splice site mutation inherited from the African American mother, and the major Finnish mutation (<a href="#0001">609883.0001</a>) inherited from the Caucasian father. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17377820" 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> rs386834048 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs386834048;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/rs386834048?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=rs386834048" 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=rs386834048" 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=RCV000022415 OR RCV000201633 OR RCV000341018 OR RCV000605128 OR RCV000666711 OR RCV000694137 OR RCV001123802 OR RCV004018536 OR RCV004528065" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022415, RCV000201633, RCV000341018, RCV000605128, RCV000666711, RCV000694137, RCV001123802, RCV004018536, RCV004528065" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022415...</a>
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<p>In 2 unrelated fetuses with Meckel syndrome (MKS1; <a href="/entry/249000">249000</a>), <a href="#4" class="mim-tip-reference" title="Consugar, M. B., Kubly, V. J., Lager, D. J., Hommerding, C. J., Wong, W. C., Bakker, E., Gattone, V. H., II, Torres, V. E., Breuning, M. H., Harris, P. C. <strong>Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3.</strong> Hum. Genet. 121: 591-599, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17377820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17377820</a>] [<a href="https://doi.org/10.1007/s00439-007-0341-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17377820">Consugar et al. (2007)</a> identified compound heterozygosity for 2 mutations in the MKS1 gene: a 417G-A transition in exon 4 and the major Finnish mutation (<a href="#0001">609883.0001</a>). The families were of Dutch and German origin, respectively. RT-PCR and direct sequencing showed that the 417G-A change resulted in abnormal splicing and deletion of exon 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17377820" 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 BARDET-BIEDL SYNDROME 13</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> rs137853105 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853105;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/rs137853105?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=rs137853105" 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=rs137853105" 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=RCV000001458 OR RCV000626942 OR RCV000665962 OR RCV001239533 OR RCV001578018 OR RCV001729331 OR RCV002465439 OR RCV004532272 OR RCV004566669" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001458, RCV000626942, RCV000665962, RCV001239533, RCV001578018, RCV001729331, RCV002465439, RCV004532272, RCV004566669" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001458...</a>
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<p>In a 2-year-old child of Turkish descent with Bardet-Biedl syndrome-13 (BBS13; <a href="/entry/615990">615990</a>), <a href="#8" class="mim-tip-reference" title="Leitch, C. C., Zaghloul, N. A., Davis, E. E., Stoetzel, C., Diaz-Font, A., Rix, S., Alfadhel, M., Lewis, R. A., Eyaid, W., Banin, E., Dollfus, H., Beales, P. L., Badano, J. L., Katsanis, N. <strong>Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome.</strong> Nature Genet. 40: 443-448, 2008. Note: Erratum: Nature Genet. 40: 927 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327255</a>] [<a href="https://doi.org/10.1038/ng.97" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18327255">Leitch et al. (2008)</a> identified compound heterozygosity for mutations in the MKS1 gene: a cys492-to-trp (C492W) substitution, and a 3-bp deletion that removes a phenylalanine (F371del; <a href="#0007">609883.0007</a>). Neither mutation was found in 192 control chromosomes, and the patient did not have mutations in any of the 12 theretofore known BBS genes. The patient had obesity, polydactyly, and nystagmus but had not yet manifested retinitis pigmentosa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18327255" 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 BARDET-BIEDL SYNDROME 13</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">rs587777804 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777804;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=rs587777804" 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=rs587777804" 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=RCV000001459" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001459" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001459</a>
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<p>For discussion of the 3-bp deletion in the MKS1 gene resulting in deletion of phenylalanine (F371del) that was found in compound heterozygous state in a patient with Bardet-Biedl syndrome-13 (BBS13; <a href="/entry/615990">615990</a>) by <a href="#8" class="mim-tip-reference" title="Leitch, C. C., Zaghloul, N. A., Davis, E. E., Stoetzel, C., Diaz-Font, A., Rix, S., Alfadhel, M., Lewis, R. A., Eyaid, W., Banin, E., Dollfus, H., Beales, P. L., Badano, J. L., Katsanis, N. <strong>Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome.</strong> Nature Genet. 40: 443-448, 2008. Note: Erratum: Nature Genet. 40: 927 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327255</a>] [<a href="https://doi.org/10.1038/ng.97" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18327255">Leitch et al. (2008)</a>, see <a href="#0006">609883.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18327255" 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 BARDET-BIEDL SYNDROME 13</strong>
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MKS1, TYR461CYS
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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> rs730882120 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs730882120;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/rs730882120?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=rs730882120" 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=rs730882120" 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=RCV000161134 OR RCV000670058 OR RCV002515117" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000161134, RCV000670058, RCV002515117" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000161134...</a>
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<p>In a Chinese boy (RP467) with Bardet-Biedl syndrome-13 (BBS13; <a href="/entry/615990">615990</a>), <a href="#14" class="mim-tip-reference" title="Xing, D.-J., Zhang, H.-X., Huang, N., Wu, K.-C., Huang, X.-F., Huang, F., Tong, Y., Pang, C.-P., Qu, J., Jin, Z.-B. <strong>Comprehensive molecular diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing.</strong> PLoS One 9: e90599, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24608809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24608809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24608809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pone.0090599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24608809">Xing et al. (2014)</a> identified compound heterozygous mutations in the MKS1 gene: a c.1382A-G transition, resulting in a tyr461-to-cys (Y461C) substitution, and a c.1601G-A transition, resulting in an arg534-to-gln (R534Q; <a href="#0009">609883.0009</a>) substitution. The mutations were identified by high-throughput targeted exome sequencing of 144 known genes responsible for inherited retinal diseases. Both mutations affected highly conserved residues and were not found in 300 controls. The Y461C mutation was not found in the dbSNP (build 137), 1000 Genomes Project, or Exome Sequencing Project (ESP6500) databases. R534Q was found in the dbSNP database (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199910690;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs199910690</a>, frequency not provided) and at a low frequency (0.0005) in the 1000 Genomes Project database; it was not present in the Exome Sequencing Project database. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24608809" 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 BARDET-BIEDL SYNDROME 13</strong>
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MKS1, ARG534GLN (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199910690;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs199910690</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> rs199910690 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199910690;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/rs199910690?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=rs199910690" 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=rs199910690" 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=RCV000161135 OR RCV000324288 OR RCV001082780 OR RCV001252740 OR RCV001272920 OR RCV001797645 OR RCV002467638 OR RCV004724951" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000161135, RCV000324288, RCV001082780, RCV001252740, RCV001272920, RCV001797645, RCV002467638, RCV004724951" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000161135...</a>
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<p>For discussion of the arg534-to-gln (R534Q) mutation in the MKS1 gene that was found in compound heterozygous state in a patient with Bardet-Biedl syndrome-13 (BBS13; <a href="/entry/615990">615990</a>) by <a href="#14" class="mim-tip-reference" title="Xing, D.-J., Zhang, H.-X., Huang, N., Wu, K.-C., Huang, X.-F., Huang, F., Tong, Y., Pang, C.-P., Qu, J., Jin, Z.-B. <strong>Comprehensive molecular diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing.</strong> PLoS One 9: e90599, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24608809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24608809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24608809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pone.0090599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24608809">Xing et al. (2014)</a>, see <a href="#0008">609883.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24608809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 JOUBERT SYNDROME 28</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">rs886038203 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886038203;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=rs886038203" 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=rs886038203" 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=RCV000241543 OR RCV005025397" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000241543, RCV005025397" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000241543...</a>
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<p>In a 44-year-old man (COR340) with Joubert syndrome-28 (JBTS28; <a href="/entry/617121">617121</a>), <a href="#9" class="mim-tip-reference" title="Romani, M., Micalizzi, A., Kraoua, I., Dotti, M. T., Cavallin, M., Sztriha, L., Ruta, R., Mancini, F., Mazza, T., Castellana, S., Hanene, B., Carlucio, M. A., Darra, F., Mate, A., Zimmermann, A., Gouider-Khouja, N., Valente, E. M. <strong>Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome.</strong> Orphanet J. Rare Dis. 9: 72, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24886560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24886560</a>] [<a href="https://doi.org/10.1186/1750-1172-9-72" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24886560">Romani et al. (2014)</a> identified a homozygous A-to-G transition in intron 16 of the MKS1 gene (c.1461-2A-G, NG_013032.1), predicted to result in a splice site alteration. Each unaffected parent was heterozygous for the mutation, which was not found in public databases. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24886560" 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> rs754279998 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs754279998;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/rs754279998?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=rs754279998" 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=rs754279998" 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=RCV000201670 OR RCV000241545 OR RCV000414929 OR RCV000665372 OR RCV000691391 OR RCV001197092 OR RCV001272923 OR RCV002465439" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201670, RCV000241545, RCV000414929, RCV000665372, RCV000691391, RCV001197092, RCV001272923, RCV002465439" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201670...</a>
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<p>In a 2-year-old child (COR413) with Joubert syndrome-28 (JBTS28; <a href="/entry/617121">617121</a>), <a href="#9" class="mim-tip-reference" title="Romani, M., Micalizzi, A., Kraoua, I., Dotti, M. T., Cavallin, M., Sztriha, L., Ruta, R., Mancini, F., Mazza, T., Castellana, S., Hanene, B., Carlucio, M. A., Darra, F., Mate, A., Zimmermann, A., Gouider-Khouja, N., Valente, E. M. <strong>Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome.</strong> Orphanet J. Rare Dis. 9: 72, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24886560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24886560</a>] [<a href="https://doi.org/10.1186/1750-1172-9-72" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24886560">Romani et al. (2014)</a> identified compound heterozygous mutations in the MKS1 gene: an in-frame 3-bp deletion (c.1085_1088delCCT, NG_013032.1), resulting in the deletion of conserved residue Ser362, and a G-to-T transversion in intron 16 (c.1558+1G-T; <a href="#0012">609883.0012</a>), predicted to result in a splice site mutation. Each unaffected parent was heterozygous for 1 of the mutations, which were not found in public databases. Functional studies of the variants and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24886560" 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">rs886038204 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886038204;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=rs886038204" 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=rs886038204" 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=RCV000241541" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000241541" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000241541</a>
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<p>For discussion of the G-to-T transversion in intron 16 of the MKS1 gene (c.1558+1G-T, NG_013032.1) that was found in compound heterozygous state in a patient with Joubert syndrome-28 (JBTS28; <a href="/entry/617121">617121</a>) by <a href="#9" class="mim-tip-reference" title="Romani, M., Micalizzi, A., Kraoua, I., Dotti, M. T., Cavallin, M., Sztriha, L., Ruta, R., Mancini, F., Mazza, T., Castellana, S., Hanene, B., Carlucio, M. A., Darra, F., Mate, A., Zimmermann, A., Gouider-Khouja, N., Valente, E. M. <strong>Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome.</strong> Orphanet J. Rare Dis. 9: 72, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24886560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24886560</a>] [<a href="https://doi.org/10.1186/1750-1172-9-72" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24886560">Romani et al. (2014)</a>, see <a href="#0011">609883.0011</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24886560" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Auber, B., Burfeind, P., Herold, S., Schoner, K., Simson, G., Rauskolb, R., Rehder, H.
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<strong>A disease causing deletion of 29 base pairs in intron 15 in the MKS1 gene is highly associated with the campomelic variant of the Meckel-Gruber syndrome.</strong>
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Clin. Genet. 72: 454-459, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935508</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17935508" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2007.00880.x" target="_blank">Full Text</a>]
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Bialas, N. J., Inglis, P. N., Li, C., Robinson, J. F., Parker, J. D. K., Healey, M. P., Davis, E. E., Inglis, C. D., Toivonen, T., Cottell, D. C., Blacque, O. E., Quarmby, L. M., Katsanis, N., Leroux, M. R.
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<strong>Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins.</strong>
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J. Cell Sci. 122: 611-624, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208769</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208769[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=19208769" 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/10.1242/jcs.028621" target="_blank">Full Text</a>]
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Chih, B., Liu, P., Chinn, Y., Chalouni, C., Komuves, L. G., Hass, P. E., Sandoval, W., Peterson, A. S.
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<strong>A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain.</strong>
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Nature Cell Biol. 14: 61-72, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22179047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22179047</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22179047" 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/ncb2410" target="_blank">Full Text</a>]
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Consugar, M. B., Kubly, V. J., Lager, D. J., Hommerding, C. J., Wong, W. C., Bakker, E., Gattone, V. H., II, Torres, V. E., Breuning, M. H., Harris, P. C.
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<strong>Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3.</strong>
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Hum. Genet. 121: 591-599, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17377820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17377820</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17377820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Dawe, H. R., Smith, U. M., Cullinane, A. R., Gerrelli, D., Cox, P., Badano, J. L., Blair-Reid, S., Sriram, N., Katsanis, N., Attie-Bitach, T., Afford, S. C., Copp, A. J., Kelly, D. A., Gull, K., Johnson, C. A.
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<strong>The Meckel-Gruber syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.</strong>
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Hum. Molec. Genet. 16: 173-186, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17185389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17185389</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17185389" 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/ddl459" target="_blank">Full Text</a>]
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 2/19/2015.
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Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M.
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<strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong>
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Nature Genet. 38: 155-157, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16415886/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16415886</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16415886" 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/ng1714" target="_blank">Full Text</a>]
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Leitch, C. C., Zaghloul, N. A., Davis, E. E., Stoetzel, C., Diaz-Font, A., Rix, S., Alfadhel, M., Lewis, R. A., Eyaid, W., Banin, E., Dollfus, H., Beales, P. L., Badano, J. L., Katsanis, N.
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<strong>Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome.</strong>
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Nature Genet. 40: 443-448, 2008. Note: Erratum: Nature Genet. 40: 927 only, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18327255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18327255</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18327255" 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.97" target="_blank">Full Text</a>]
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</p>
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|
</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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|
<a id="Romani2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Romani, M., Micalizzi, A., Kraoua, I., Dotti, M. T., Cavallin, M., Sztriha, L., Ruta, R., Mancini, F., Mazza, T., Castellana, S., Hanene, B., Carlucio, M. A., Darra, F., Mate, A., Zimmermann, A., Gouider-Khouja, N., Valente, E. M.
|
|
<strong>Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome.</strong>
|
|
Orphanet J. Rare Dis. 9: 72, 2014. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24886560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24886560</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24886560" 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/10.1186/1750-1172-9-72" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Salonen1984" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Salonen, R.
|
|
<strong>The Meckel syndrome: clinicopathological findings in 67 patients.</strong>
|
|
Am. J. Med. Genet. 18: 671-689, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6486167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6486167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6486167" 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.1320180414" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Tammachote2009" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Tammachote, R., Hommerding, C. J., Sinders, R. M., Miller, C. A., Czarnecki, P. G., Leightner, A. C., Salisbury, J. L., Ward, C. J., Torres, V. E., Gattone, V. H., II, Harris, P. C.
|
|
<strong>Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3.</strong>
|
|
Hum. Molec. Genet. 18: 3311-3323, 2009.
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|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19515853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19515853</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19515853" 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/ddp272" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Weatherbee2009" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Weatherbee, S. D., Niswander, L. A., Anderson, K. V.
|
|
<strong>A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and hedgehog signaling.</strong>
|
|
Hum. Molec. Genet. 18: 4565-4575, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19776033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19776033</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19776033[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=19776033" 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/ddp422" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Williams2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Williams, C. L., Li, C., Kida, K., Inglis, P. N., Mohan, S., Semenec, L., Bialas, N. J., Stupay, R. M., Chen, N., Blacque, O. E., Yoder, B. K., Leroux, M. R.
|
|
<strong>MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.</strong>
|
|
J. Cell. Biol. 192: 1023-1041, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21422230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21422230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21422230[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=21422230" 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/10.1083/jcb.201012116" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Xing2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Xing, D.-J., Zhang, H.-X., Huang, N., Wu, K.-C., Huang, X.-F., Huang, F., Tong, Y., Pang, C.-P., Qu, J., Jin, Z.-B.
|
|
<strong>Comprehensive molecular diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing.</strong>
|
|
PLoS One 9: e90599, 2014. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24608809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24608809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24608809[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=24608809" 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/10.1371/journal.pone.0090599" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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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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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
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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">
|
|
Cassandra L. Kniffin - updated : 09/22/2016
|
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</span>
|
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</div>
|
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</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Matthew B. Gross - updated : 2/19/2015<br>Cassandra L. Kniffin - updated : 2/12/2015<br>Patricia A. Hartz - updated : 11/27/2012<br>Patricia A. Hartz - updated : 8/5/2011<br>Patricia A. Hartz - updated : 4/29/2011<br>George E. Tiller - updated : 10/28/2010<br>George E. Tiller - updated : 7/7/2010<br>Patricia A. Hartz - updated : 6/25/2010<br>Cassandra L. Kniffin - updated : 8/22/2008<br>Ada Hamosh - updated : 5/7/2008<br>Cassandra L. Kniffin - updated : 6/6/2007
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
|
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<div class="row">
|
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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">
|
|
Creation Date:
|
|
</span>
|
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 2/9/2006
|
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</span>
|
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</div>
|
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
|
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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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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 04/25/2023
|
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</span>
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</div>
|
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</div>
|
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<div class="row collapse" id="mimCollapseEditHistory">
|
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 12/02/2020<br>carol : 09/23/2016<br>ckniffin : 09/22/2016<br>alopez : 07/23/2015<br>mgross : 2/19/2015<br>carol : 2/18/2015<br>carol : 2/18/2015<br>carol : 2/18/2015<br>mcolton : 2/18/2015<br>ckniffin : 2/12/2015<br>alopez : 10/23/2014<br>alopez : 10/16/2014<br>alopez : 11/27/2012<br>terry : 11/27/2012<br>carol : 11/22/2011<br>wwang : 8/5/2011<br>terry : 8/5/2011<br>mgross : 5/19/2011<br>mgross : 5/19/2011<br>terry : 4/29/2011<br>wwang : 11/9/2010<br>terry : 10/28/2010<br>wwang : 7/20/2010<br>terry : 7/7/2010<br>mgross : 6/30/2010<br>mgross : 6/30/2010<br>terry : 6/25/2010<br>wwang : 9/2/2008<br>ckniffin : 8/22/2008<br>alopez : 7/14/2008<br>alopez : 5/23/2008<br>alopez : 5/23/2008<br>alopez : 5/23/2008<br>terry : 5/7/2008<br>wwang : 6/14/2007<br>ckniffin : 6/6/2007<br>alopez : 2/9/2006
|
|
</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 609883
|
|
</span>
|
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</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
MKS TRANSITION ZONE COMPLEX SUBUNIT 1; MKS1
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
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</div>
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<div>
|
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<div >
|
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MKS1 GENE<br />
|
|
BBS13 GENE; BBS13<br />
|
|
FLJ20345
|
|
</span>
|
|
</h4>
|
|
</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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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: MKS1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 17q22
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 17:58,205,441-58,219,255 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<br />
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
17q22
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Bardet-Biedl syndrome 13
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
615990
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Joubert syndrome 28
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617121
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Meckel syndrome 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
249000
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
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|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</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>MKS1 belongs to a small family of B9 domain-containing proteins that also includes B9D1 (614144) and B9D2 (611951), and all 3 B9 domain-containing proteins associate with basal bodies and primary cilia in mammalian cells (summary by Bialas et al., 2009). </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>Kyttala et al. (2006) identified the MKS1 gene (FLJ20345) in a 100-kb region of chromosome 17q23 to which Meckel syndrome had been linked in Finnish families. The gene contains an open reading frame (bp 76-1755) coding for a 559-amino acid polypeptide containing a conserved B9 domain. Comparison of sequence across human, mouse, zebrafish, fruit fly, and C. elegans showed high conservation. Human and mouse coding regions are 86 to 88% similar at the nucleotide level and 89% at the amino acid level. In situ hybridization analyses showed a relatively broad tissue expression of Mks1 in mouse embryo at embryonic day 15.5. The expression was especially prominent in tissues showing malformations characteristic of Meckel syndrome: brain, liver, kidney, and digits of the upper limbs. Highest expression was observed in bronchiolar epithelium. Hypoplastic lungs are frequently reported in MKS patients, but this feature had been presumed to be caused by lack of amniotic fluid and mechanical pressure from the enlarged kidneys. </p><p>By immunohistochemical analysis of 18- to 20-week-old human fetal kidneys, Dawe et al. (2007) found moderate to high expression of meckelin (MKS3, or TMEM67; 609884) and MKS1 at the proximal renal tubule epithelia, but not at glomeruli. In liver, these proteins were expressed at the biliary epithelium of larger bile ducts, but not in hepatocytes. In biliary epithelial cells, MKS1 showed a clear punctate doublet staining pattern characteristic of a centrosomal localization. In HEK293 cells, MKS1 showed a broad intracellular localization with occasional distribution at the cell border. Western blot analysis detected MKS1 at an apparent molecular mass of 70 kD. </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 RNA interference, Dawe et al. (2007) found that knockdown of either Mks1 or Mks3 in mouse inner medullary IMCD-3 cells blocked centriole migration to the apical membrane and formation of the primary cilium. Coimmunoprecipitation experiments showed that wildtype Mks1 and Mks3 interacted, and knockdown of either Mks1 or Mks3 in IMCD-3 cells decreased the formation of highly branched structures and tubules in 3-dimensional cultures. Dawe et al. (2007) concluded that MKS1 and MKS3 have roles in ciliogenesis and renal tubulogenesis. </p><p>Tammachote et al. (2009) showed that kidney tissue and cells from MKS1 and MKS3 (607361) patients showed defects in centrosome and cilia number, including multiciliated respiratory-like epithelia, and longer cilia. Stable shRNA knockdown of Mks1 and Mks3 in IMCD-3 cells induced multiciliated and multicentrosomal phenotypes. MKS1 and MKS3 functions are required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. Tammachote et al. (2009) concluded that MKS1 and MKS3 are ciliopathies, with new cilia-related eye and sperm phenotypes defined. </p><p>Williams et al. (2011) showed that the conserved proteins Mks1, Mksr1 (B9D1), Mksr2 (B9D2; 611951), Tmem67, Rpgrip1l (610937), Cc2d2a (612013), Nphp1 (607100), and Nphp4 (607215) functioned at an early stage of ciliogenesis in C. elegans. These 8 proteins localized to the ciliary transition zone and established attachments between the basal body and transition zone membrane. They also provided a docking site that restricted vesicle fusion to vesicles containing ciliary proteins. </p><p>Using tandem affinity purification and mass spectrometry to isolate proteins that purified with B9d1 (614144) in mouse IMCD3 cells and embryonic fibroblasts, Chih et al. (2012) identified several components of the B9d1-containing ciliary complex, including Tmem231 (614949), Tmem17 (614950), B9d2 (611951), Tctn1 (609863), Tctn2 (613846), Mks1, Ahi1 (608894), Cc2d2a (612013), and Kctd10 (613421). </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>Kyttala et al. (2006) determined that the 14-kb MKS1 gene contains 18 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>Kyttala et al. (2006) stated that the FLJ20345 gene (MKS1 gene) is on chromosome 17q23. The mouse homolog maps to a region of chromosome 11 demonstrating homology of synteny with human 17q23. </p><p>Gross (2015) mapped the MKS1 gene to chromosome 17q22 based on an alignment of the MKS1 sequence (GenBank BC010061) with the genomic sequence (GRCh38).</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>Evolution</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 database analysis, Bialas et al. (2009) found orthologs of B9D1, B9D2, and MKS1 in the vast majority of ciliated species, but not in nonciliated organisms. The 3 B9 domain-containing proteins appeared to be evolutionarily ancient, and the duplications resulting in the 3 protein clades preceded speciation. </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>Meckel Syndrome 1</em></strong></p><p>
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Meckel syndrome (MKS) is a severe autosomal recessive fetal developmental disorder. The clinical hallmarks are occipital meningoencephalocele, cystic kidney dysplasia, fibrotic changes of the liver, and polydactyly. Genetic heterogeneity was established by genome linkage scans. The MKS1 locus on 17q (249000) was identified in Finnish families. Kyttala et al. (2006) found that in Finnish families in which the MKS1 locus was identified, 70% of the patients were homozygous for the same haplotype on 17q23. Sequence analysis of the MKS1 gene showed a 29-bp deletion in intron 15 (609883.0001) in 3 Finnish families sharing the MKS1 haplotype and in 1 German patient with evidence of linkage to 17q23. This deletion was located only 4 bp away from the splice acceptor site and was predicted to interrupt the splice branching site. The intronic deletion was detected as a size difference in PCR products from genomic DNA, and analysis of DNA samples of 26 Finnish families with the common founder haplotype confirmed that all individuals were homozygous, and that parents were heterozygous, for this deletion. Comparative genomics and proteomics data implicated MKS1 in ciliary function. Review of the series of 67 Finnish MKS patients reported by Salonen (1984) showed 3 cases with situs inversus totalis (see 270100), which implied an increased risk for this rare condition in Meckel syndrome and would provide another link to ciliary dysfunction. </p><p>Consugar et al. (2007) identified mutations in the MKS1 gene in affected individuals in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All 5 families had the major Finnish deletion mutation: 2 were homozygous, and 3 were compound heterozygous with another pathogenic mutation (609883.0004 and 609883.0005). </p><p><strong><em>Bardet-Biedl Syndrome 13</em></strong></p><p>
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Leitch et al. (2008) demonstrated that mutations in MKS1, MKS3 (609884), and CEP290 (610142) either can cause Bardet-Biedl syndrome (see 209900) or may have a potential epistatic effect on mutations in known BBS-associated loci. Five of 6 families with both MKS1 and BBS mutations manifested seizures, a feature that is not a typical component of either Meckel or Bardet-Biedl syndrome. Functional studies in zebrafish showed that mks1 is necessary for gastrulation movements and that it interacts genetically with known bbs genes. In 1 patient compound heterozygous mutations in MKS1 resulting in the BBS phenotype were found (see 609883.0006). In 5 families a single heterozygous mutation in MKS1 was found. Two of these families also carried mutations in BBS10 (610148), and a third family carried a homozygous mutation in BBS1 (209901). Leitch et al. (2008) concluded that their data extended the genetic stratification of ciliopathies and suggested that BBS and MKS, although distinct clinically, are allelic forms of the same molecular spectrum. </p><p>In a Chinese boy with BBS13, Xing et al. (2014) identified compound heterozygous missense mutations in the MKS1 gene (Y461C; 609883.0008) and R534Q (609883.0009). The mutations were identified by high-throughput targeted exome sequencing of 144 known genes responsible for inherited retinal diseases. Functional studies of the variants were not performed. </p><p><strong><em>Joubert Syndrome 28</em></strong></p><p>
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In 2 unrelated patients with Joubert syndrome-28 (JBTS28; 617121), Romani et al. (2014) identified biallelic mutations in the MKS1 gene (609883.0010-609883.0012). Functional studies of the variants and studies of patient cells were not performed. The patients were part of a group of 260 JBTS patients who were screened for mutations in ciliopathy genes. </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>Weatherbee et al. (2009) showed that loss of function of mouse Mks1 resulted in an accurate model of Meckel syndrome, with structural abnormalities in the neural tube, biliary duct, limb patterning, bone development, and the kidney. In contrast to cell culture studies, loss of Mks1 in vivo did not interfere with apical localization of epithelial basal bodies, but rather led to defective cilia formation in most, but not all, tissues. Analysis of patterning in the neural tube and the limb demonstrated altered Hedgehog (Hh) pathway signaling underlying some MKS defects, although both tissues showed an expansion of the domain of response to Shh (600725) signaling, unlike the phenotypes seen in other mutants with cilia loss. Other defects in the skull, lung, rib cage, and long bones were thought likely to be the result of disruption of Hh signaling. Weatherbee et al. (2009) concluded that disruption of Hh signaling may explain many, but not all, of the defects caused by loss of Mks1. </p><p>Bialas et al. (2009) disrupted the B9 domains of C. elegans mks1, mksr1, and mksr2. In contrast to the defect found in mouse cells, C. elegans expressing single, double, or triple mks/mksr mutants showed no overt defects in ciliary structure, nor in intraflagellar transport, chemosensation, osmosensation, or lipid accumulation. However, disruption of one B9 domain-containing protein resulted in mislocalization of the others, and all possible double mks/mksr mutant combinations altered insulin signaling, leading to increased life span. The mks1/mksr1/mksr2 triple mutant did not exhibit a longevity phenotype. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<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>12 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 MECKEL SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MKS1, 29-BP DEL
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<br />
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SNP: rs386834043,
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ClinVar: RCV000168467, RCV000210823, RCV000273342, RCV000491550, RCV000984005, RCV002515190, RCV003474892, RCV004528921, RCV005016510
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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 3 Finnish families sharing the founder MKS1 haplotype and in 1 German patient with evidence of linkage of Meckel syndrome to 17q23 (MKS1; 249000), Kyttala et al. (2006) found that the MKS1 gene showed a 29-bp deletion in intron 15 as the cause of the anomaly. This deletion was located only 4 bp away from the splice acceptor site and probably interrupted the splice branching site. The same intronic deletion was found in 26 Finnish families with a common founder haplotype; all affected individuals were homozygous, and the parents heterozygous, for the deletion, which Kyttala et al. (2006) called the MKS1-Fin(major) mutation. This mutation was also found in an American family and in a family of mixed Swedish-Portuguese-Irish descent. </p><p>Auber et al. (2007) identified the 29-bp deletion in intron 15 of the MKS1 gene in 8 of 20 unrelated fetuses diagnosed clinically with MKS. Six cases, consisting of 1 heterozygous and 5 homozygous mutations, had the campomelic variant of the disorder. The carrier frequency of this mutation in the German population was determined to be 1 in 260. </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 MECKEL SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MKS1, 5-BP INS, NT50
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<br />
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SNP: rs730880323,
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ClinVar: RCV000022412
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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 case of Meckel syndrome (MKS1; 249000) of German ancestry, Kyttala et al. (2006) found compound heterozygosity for mutations in MKS1 located at the very beginning of the transcript: a 5-bp insertion in exon 1 (50insCCGGG), causing a frameshift (Pro17fsTer163); and a T-to-C substitution at the splice donor site of intron 1 (IVS1+2T-C; 609883.0003). </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">
|
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<strong>.0003 MECKEL SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MKS1, IVS1DS, T-C, +2
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<br />
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SNP: rs386834052,
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ClinVar: RCV000022413, RCV000665702
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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 splice site mutation in intron 1 of the MKS1 gene (IVS1+2T-C) that was found in compound heterozygous state in a patient with Meckel syndrome (MKS1; 249000) by Kyttala et al. (2006), see 609883.0002. </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 MECKEL SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MKS1, IVS11DS, G-A, +1
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<br />
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SNP: rs199874059,
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gnomAD: rs199874059,
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ClinVar: RCV000022414, RCV000668139, RCV001038005, RCV001570919, RCV003472957, RCV004732522
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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 16-week-old fetus with Meckel syndrome (MKS1; 249000) diagnosed by ultrasound, Consugar et al. (2007) identified compound heterozygosity for 2 mutations in the MKS1 gene: a G-to-A transition in intron 11 (IVS11+1G-A), resulting in a splice site mutation inherited from the African American mother, and the major Finnish mutation (609883.0001) inherited from the Caucasian father. </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>.0005 MECKEL SYNDROME, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MKS1, 417G-A
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<br />
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SNP: rs386834048,
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gnomAD: rs386834048,
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ClinVar: RCV000022415, RCV000201633, RCV000341018, RCV000605128, RCV000666711, RCV000694137, RCV001123802, RCV004018536, RCV004528065
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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 2 unrelated fetuses with Meckel syndrome (MKS1; 249000), Consugar et al. (2007) identified compound heterozygosity for 2 mutations in the MKS1 gene: a 417G-A transition in exon 4 and the major Finnish mutation (609883.0001). The families were of Dutch and German origin, respectively. RT-PCR and direct sequencing showed that the 417G-A change resulted in abnormal splicing and deletion of exon 4. </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>.0006 BARDET-BIEDL SYNDROME 13</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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MKS1, CYS492TRP
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<br />
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SNP: rs137853105,
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gnomAD: rs137853105,
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ClinVar: RCV000001458, RCV000626942, RCV000665962, RCV001239533, RCV001578018, RCV001729331, RCV002465439, RCV004532272, RCV004566669
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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 2-year-old child of Turkish descent with Bardet-Biedl syndrome-13 (BBS13; 615990), Leitch et al. (2008) identified compound heterozygosity for mutations in the MKS1 gene: a cys492-to-trp (C492W) substitution, and a 3-bp deletion that removes a phenylalanine (F371del; 609883.0007). Neither mutation was found in 192 control chromosomes, and the patient did not have mutations in any of the 12 theretofore known BBS genes. The patient had obesity, polydactyly, and nystagmus but had not yet manifested retinitis pigmentosa. </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>.0007 BARDET-BIEDL SYNDROME 13</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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MKS1, 3-BP DEL, PHE371DEL
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<br />
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SNP: rs587777804,
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ClinVar: RCV000001459
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the 3-bp deletion in the MKS1 gene resulting in deletion of phenylalanine (F371del) that was found in compound heterozygous state in a patient with Bardet-Biedl syndrome-13 (BBS13; 615990) by Leitch et al. (2008), see 609883.0006. </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>.0008 BARDET-BIEDL SYNDROME 13</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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MKS1, TYR461CYS
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<br />
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SNP: rs730882120,
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gnomAD: rs730882120,
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ClinVar: RCV000161134, RCV000670058, RCV002515117
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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 Chinese boy (RP467) with Bardet-Biedl syndrome-13 (BBS13; 615990), Xing et al. (2014) identified compound heterozygous mutations in the MKS1 gene: a c.1382A-G transition, resulting in a tyr461-to-cys (Y461C) substitution, and a c.1601G-A transition, resulting in an arg534-to-gln (R534Q; 609883.0009) substitution. The mutations were identified by high-throughput targeted exome sequencing of 144 known genes responsible for inherited retinal diseases. Both mutations affected highly conserved residues and were not found in 300 controls. The Y461C mutation was not found in the dbSNP (build 137), 1000 Genomes Project, or Exome Sequencing Project (ESP6500) databases. R534Q was found in the dbSNP database (rs199910690, frequency not provided) and at a low frequency (0.0005) in the 1000 Genomes Project database; it was not present in the Exome Sequencing Project database. Functional studies of the variants were not performed. </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>.0009 BARDET-BIEDL SYNDROME 13</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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MKS1, ARG534GLN ({dbSNP rs199910690})
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<br />
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SNP: rs199910690,
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gnomAD: rs199910690,
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ClinVar: RCV000161135, RCV000324288, RCV001082780, RCV001252740, RCV001272920, RCV001797645, RCV002467638, RCV004724951
|
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|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of the arg534-to-gln (R534Q) mutation in the MKS1 gene that was found in compound heterozygous state in a patient with Bardet-Biedl syndrome-13 (BBS13; 615990) by Xing et al. (2014), see 609883.0008. </p>
|
|
</span>
|
|
</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>.0010 JOUBERT SYNDROME 28</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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MKS1, IVS16AS, A-G, -2
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<br />
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SNP: rs886038203,
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|
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ClinVar: RCV000241543, RCV005025397
|
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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 44-year-old man (COR340) with Joubert syndrome-28 (JBTS28; 617121), Romani et al. (2014) identified a homozygous A-to-G transition in intron 16 of the MKS1 gene (c.1461-2A-G, NG_013032.1), predicted to result in a splice site alteration. Each unaffected parent was heterozygous for the mutation, which was not found in public databases. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</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>.0011 JOUBERT SYNDROME 28</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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MKS1, 3-BP DEL, 1085CCT
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<br />
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SNP: rs754279998,
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gnomAD: rs754279998,
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ClinVar: RCV000201670, RCV000241545, RCV000414929, RCV000665372, RCV000691391, RCV001197092, RCV001272923, RCV002465439
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old child (COR413) with Joubert syndrome-28 (JBTS28; 617121), Romani et al. (2014) identified compound heterozygous mutations in the MKS1 gene: an in-frame 3-bp deletion (c.1085_1088delCCT, NG_013032.1), resulting in the deletion of conserved residue Ser362, and a G-to-T transversion in intron 16 (c.1558+1G-T; 609883.0012), predicted to result in a splice site mutation. Each unaffected parent was heterozygous for 1 of the mutations, which were not found in public databases. Functional studies of the variants and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 JOUBERT SYNDROME 28</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
MKS1, IVS16DS, G-T, +1
|
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<br />
|
|
|
|
SNP: rs886038204,
|
|
|
|
|
|
|
|
ClinVar: RCV000241541
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the G-to-T transversion in intron 16 of the MKS1 gene (c.1558+1G-T, NG_013032.1) that was found in compound heterozygous state in a patient with Joubert syndrome-28 (JBTS28; 617121) by Romani et al. (2014), see 609883.0011. </p>
|
|
</span>
|
|
</div>
|
|
|
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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>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Auber, B., Burfeind, P., Herold, S., Schoner, K., Simson, G., Rauskolb, R., Rehder, H.
|
|
<strong>A disease causing deletion of 29 base pairs in intron 15 in the MKS1 gene is highly associated with the campomelic variant of the Meckel-Gruber syndrome.</strong>
|
|
Clin. Genet. 72: 454-459, 2007.
|
|
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|
|
[PubMed: 17935508]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00880.x]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Bialas, N. J., Inglis, P. N., Li, C., Robinson, J. F., Parker, J. D. K., Healey, M. P., Davis, E. E., Inglis, C. D., Toivonen, T., Cottell, D. C., Blacque, O. E., Quarmby, L. M., Katsanis, N., Leroux, M. R.
|
|
<strong>Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins.</strong>
|
|
J. Cell Sci. 122: 611-624, 2009.
|
|
|
|
|
|
[PubMed: 19208769]
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|
|
[Full Text: https://doi.org/10.1242/jcs.028621]
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|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Chih, B., Liu, P., Chinn, Y., Chalouni, C., Komuves, L. G., Hass, P. E., Sandoval, W., Peterson, A. S.
|
|
<strong>A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain.</strong>
|
|
Nature Cell Biol. 14: 61-72, 2012.
|
|
|
|
|
|
[PubMed: 22179047]
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|
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|
|
|
[Full Text: https://doi.org/10.1038/ncb2410]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Consugar, M. B., Kubly, V. J., Lager, D. J., Hommerding, C. J., Wong, W. C., Bakker, E., Gattone, V. H., II, Torres, V. E., Breuning, M. H., Harris, P. C.
|
|
<strong>Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3.</strong>
|
|
Hum. Genet. 121: 591-599, 2007.
|
|
|
|
|
|
[PubMed: 17377820]
|
|
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|
|
|
[Full Text: https://doi.org/10.1007/s00439-007-0341-3]
|
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|
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</p>
|
|
</li>
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Dawe, H. R., Smith, U. M., Cullinane, A. R., Gerrelli, D., Cox, P., Badano, J. L., Blair-Reid, S., Sriram, N., Katsanis, N., Attie-Bitach, T., Afford, S. C., Copp, A. J., Kelly, D. A., Gull, K., Johnson, C. A.
|
|
<strong>The Meckel-Gruber syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.</strong>
|
|
Hum. Molec. Genet. 16: 173-186, 2007.
|
|
|
|
|
|
[PubMed: 17185389]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddl459]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 2/19/2015.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kyttala, M., Tallila, J., Salonen, R., Kopra, O., Kohlschmidt, N., Paavola-Sakki, P., Peltonen, L., Kestila, M.
|
|
<strong>MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.</strong>
|
|
Nature Genet. 38: 155-157, 2006.
|
|
|
|
|
|
[PubMed: 16415886]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1714]
|
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|
|
</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leitch, C. C., Zaghloul, N. A., Davis, E. E., Stoetzel, C., Diaz-Font, A., Rix, S., Alfadhel, M., Lewis, R. A., Eyaid, W., Banin, E., Dollfus, H., Beales, P. L., Badano, J. L., Katsanis, N.
|
|
<strong>Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome.</strong>
|
|
Nature Genet. 40: 443-448, 2008. Note: Erratum: Nature Genet. 40: 927 only, 2008.
|
|
|
|
|
|
[PubMed: 18327255]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.97]
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Romani, M., Micalizzi, A., Kraoua, I., Dotti, M. T., Cavallin, M., Sztriha, L., Ruta, R., Mancini, F., Mazza, T., Castellana, S., Hanene, B., Carlucio, M. A., Darra, F., Mate, A., Zimmermann, A., Gouider-Khouja, N., Valente, E. M.
|
|
<strong>Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome.</strong>
|
|
Orphanet J. Rare Dis. 9: 72, 2014. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 24886560]
|
|
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|
|
[Full Text: https://doi.org/10.1186/1750-1172-9-72]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Salonen, R.
|
|
<strong>The Meckel syndrome: clinicopathological findings in 67 patients.</strong>
|
|
Am. J. Med. Genet. 18: 671-689, 1984.
|
|
|
|
|
|
[PubMed: 6486167]
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|
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|
|
[Full Text: https://doi.org/10.1002/ajmg.1320180414]
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tammachote, R., Hommerding, C. J., Sinders, R. M., Miller, C. A., Czarnecki, P. G., Leightner, A. C., Salisbury, J. L., Ward, C. J., Torres, V. E., Gattone, V. H., II, Harris, P. C.
|
|
<strong>Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3.</strong>
|
|
Hum. Molec. Genet. 18: 3311-3323, 2009.
|
|
|
|
|
|
[PubMed: 19515853]
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|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp272]
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|
|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Weatherbee, S. D., Niswander, L. A., Anderson, K. V.
|
|
<strong>A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and hedgehog signaling.</strong>
|
|
Hum. Molec. Genet. 18: 4565-4575, 2009.
|
|
|
|
|
|
[PubMed: 19776033]
|
|
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddp422]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Williams, C. L., Li, C., Kida, K., Inglis, P. N., Mohan, S., Semenec, L., Bialas, N. J., Stupay, R. M., Chen, N., Blacque, O. E., Yoder, B. K., Leroux, M. R.
|
|
<strong>MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.</strong>
|
|
J. Cell. Biol. 192: 1023-1041, 2011.
|
|
|
|
|
|
[PubMed: 21422230]
|
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|
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|
|
[Full Text: https://doi.org/10.1083/jcb.201012116]
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|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Xing, D.-J., Zhang, H.-X., Huang, N., Wu, K.-C., Huang, X.-F., Huang, F., Tong, Y., Pang, C.-P., Qu, J., Jin, Z.-B.
|
|
<strong>Comprehensive molecular diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing.</strong>
|
|
PLoS One 9: e90599, 2014. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 24608809]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1371/journal.pone.0090599]
|
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|
|
</p>
|
|
</li>
|
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</ol>
|
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|
|
<div>
|
|
<br />
|
|
</div>
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|
</div>
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|
</div>
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<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 09/22/2016<br>Matthew B. Gross - updated : 2/19/2015<br>Cassandra L. Kniffin - updated : 2/12/2015<br>Patricia A. Hartz - updated : 11/27/2012<br>Patricia A. Hartz - updated : 8/5/2011<br>Patricia A. Hartz - updated : 4/29/2011<br>George E. Tiller - updated : 10/28/2010<br>George E. Tiller - updated : 7/7/2010<br>Patricia A. Hartz - updated : 6/25/2010<br>Cassandra L. Kniffin - updated : 8/22/2008<br>Ada Hamosh - updated : 5/7/2008<br>Cassandra L. Kniffin - updated : 6/6/2007
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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<div>
|
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<div class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
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Victor A. McKusick : 2/9/2006
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carol : 04/25/2023<br>carol : 12/02/2020<br>carol : 09/23/2016<br>ckniffin : 09/22/2016<br>alopez : 07/23/2015<br>mgross : 2/19/2015<br>carol : 2/18/2015<br>carol : 2/18/2015<br>carol : 2/18/2015<br>mcolton : 2/18/2015<br>ckniffin : 2/12/2015<br>alopez : 10/23/2014<br>alopez : 10/16/2014<br>alopez : 11/27/2012<br>terry : 11/27/2012<br>carol : 11/22/2011<br>wwang : 8/5/2011<br>terry : 8/5/2011<br>mgross : 5/19/2011<br>mgross : 5/19/2011<br>terry : 4/29/2011<br>wwang : 11/9/2010<br>terry : 10/28/2010<br>wwang : 7/20/2010<br>terry : 7/7/2010<br>mgross : 6/30/2010<br>mgross : 6/30/2010<br>terry : 6/25/2010<br>wwang : 9/2/2008<br>ckniffin : 8/22/2008<br>alopez : 7/14/2008<br>alopez : 5/23/2008<br>alopez : 5/23/2008<br>alopez : 5/23/2008<br>terry : 5/7/2008<br>wwang : 6/14/2007<br>ckniffin : 6/6/2007<br>alopez : 2/9/2006
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