4427 lines
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Entry
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- *604896 - MKKS CENTROSOMAL SHUTTLING PROTEIN; MKKS
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- OMIM
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<p>
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<span class="h4">*604896</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604896">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div 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 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=ENSG00000125863;t=ENST00000347364" 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=8195" 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=604896" 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=ENSG00000125863;t=ENST00000347364" 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_018848,NM_170784,NR_072977" 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_170784" 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=604896" 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=05356&isoform_id=05356_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/MKKS" 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/7018457,8163832,8163834,9055272,10438353,11133565,23468372,25914754,119630748,119630749,119630750,158257282,221041356,440575919" 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/Q9NPJ1" 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=8195" 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=ENSG00000125863;t=ENST00000347364" 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=MKKS" 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=MKKS" 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+8195" 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/MKKS" 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:8195" 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/8195" 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=chr20&hgg_gene=ENST00000347364.7&hgg_start=10401009&hgg_end=10434222&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:7108" 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:7108" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/mkks" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604896[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=604896[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000125863" 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=MKKS" 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=MKKS" 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=MKKS" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://www.euro-wabb.org/en/lovd-genetic-variation-database" title="EURO-WABB Project Open Variation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">EURO-WABB Project Open Var…</a></div><div style="margin-left: 0.5em;"><a href="http://www.retina-international.org/files/sci-news/mkksmut.htm" title="Mutations of the McKusick-Kaufman Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Mutations of the McKusick-…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=MKKS&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/PA30826" 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:7108" 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://www.mousephenotype.org/data/genes/MGI:1891836" 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/MKKS#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:1891836" 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/8195/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=8195" 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://zfin.org/ZDB-GENE-040426-757" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=MKKS&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 702407009<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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604896
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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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MKKS CENTROSOMAL SHUTTLING PROTEIN; MKKS
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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MKKS GENE<br />
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MKS<br />
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BBS6 GENE; BBS6
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MKKS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MKKS</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
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<em>
|
|
Cytogenetic location: <a href="/geneMap/20/97?start=-3&limit=10&highlight=97">20p12.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr20:10401009-10434222&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'})">20:10,401,009-10,434,222</a> </span>
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</em>
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=605231,236700" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
|
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</th>
|
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
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Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
|
</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/20/97?start=-3&limit=10&highlight=97">
|
|
20p12.2
|
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</a>
|
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</span>
|
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</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Bardet-Biedl syndrome 6
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/605231"> 605231 </a>
|
|
|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
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<span class="mim-font">
|
|
McKusick-Kaufman syndrome
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/236700"> 236700 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
|
</td>
|
|
</tr>
|
|
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|
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</tbody>
|
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</table>
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<p><a href="#19" class="mim-tip-reference" title="Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G. <strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong> Nature Genet. 25: 79-82, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802661</a>] [<a href="https://doi.org/10.1038/75637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802661">Stone et al. (2000)</a> analyzed the approximately 450-kb critical region on chromosome 20p12 for McKusick-Kaufman syndrome (MKKS; <a href="/entry/236700">236700</a>) by sample sequencing, which revealed the presence of several known genes and EST clusters. Candidate transcripts were evaluated by Northern blot analysis of adult and fetal tissues. They selected 1 transcript with widespread expression for analysis in a patient from an Amish pedigree and a sporadic, non-Amish case. The Old Order Amish patient was found to be homozygous for an allele that had 2 missense substitutions, and the non-Amish patient was compound heterozygous for a frameshift mutation predicting premature protein truncation and a distinct missense mutation. The MKKS transcript has a predicted open reading frame of 570 amino acids Northern blot analysis revealed broad expression of a 2.4-kb transcript in human adult and fetal tissues. The MKKS predicted protein showed amino acid similarity to the chaperonin family of proteins (see <a href="/entry/118190">118190</a>), suggesting a role for protein processing in limb, cardiac, and reproductive system development. Its closest protein relative is the alpha subunit of the Thermoplasma acidophilum thermosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#19" class="mim-tip-reference" title="Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G. <strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong> Nature Genet. 25: 79-82, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802661</a>] [<a href="https://doi.org/10.1038/75637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802661">Stone et al. (2000)</a> determined that the MKKS gene has 6 exons with a start codon in exon 3 and 2 alternative 5-prime terminal exons that are noncoding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#19" class="mim-tip-reference" title="Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G. <strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong> Nature Genet. 25: 79-82, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802661</a>] [<a href="https://doi.org/10.1038/75637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802661">Stone et al. (2000)</a> modeled the 3-dimensional structure of the MKKS protein using data from the x-ray crystal structure of the T. acidophilum group II chaperonin protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802661" 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 live cell imaging techniques, <a href="#6" class="mim-tip-reference" title="Hirayama, S., Yamazaki, Y., Kitamura, A., Oda, Y., Morito, D., Okawa, K., Kimura, H., Cyr, D. M., Kubota, H., Nagata, K. <strong>MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination.</strong> Molec. Biol. Cell 19: 899-911, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18094050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18094050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18094050[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/10.1091/mbc.e07-07-0631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18094050">Hirayama et al. (2008)</a> observed that MKKS was highly mobile and rapidly shuttled between the cytosol and centrosome. Several disease-associated mutations altered the degradation and/or solubility of the MKKS protein. The mutations T57A (<a href="#0010">604896.0010</a>), C499S (<a href="#0013">604896.0013</a>), and Y37C (<a href="#0003">604896.0003</a>) caused both increased MKKS degradation and reduced solubility relative to wildtype MKKS, and the H84Y (<a href="#0001">604896.0001</a>), whereas the A242S, R155L, and G345E mutations increased MKKS degradation only. Proteasome inhibition resulted in aggregation of the G345E mutant at the centrosome; however, the Y37C mutant was immobilized at the centrosome even in the absence of proteasome inhibition. The G345E and Y37C mutants were also highly polyubiquitinated, and immunoprecipitation analysis revealed that the rapidly degraded G345E mutant was recognized by components of the ubiquitin-proteasome protein degradation pathway, HSP70 (see HSPA1A; <a href="/entry/140550">140550</a>), HSC70 (HSPA8; <a href="/entry/600816">600816</a>), HSP90 (see HSPCA; <a href="/entry/140571">140571</a>), and CHIP (STUB1; <a href="/entry/607207">607207</a>). Knockdown of CHIP by RNA interference reduced the polyubiquitination and degradation of the G345E mutant protein. <a href="#6" class="mim-tip-reference" title="Hirayama, S., Yamazaki, Y., Kitamura, A., Oda, Y., Morito, D., Okawa, K., Kimura, H., Cyr, D. M., Kubota, H., Nagata, K. <strong>MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination.</strong> Molec. Biol. Cell 19: 899-911, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18094050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18094050</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18094050[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/10.1091/mbc.e07-07-0631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18094050">Hirayama et al. (2008)</a> concluded that CHIP activity modulates the aggregation and stability of some MKKS mutant proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18094050" 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>Mice homozygous for the rd16 truncation mutation in the centrosomal protein Cep290 (<a href="/entry/610142">610142</a>) develop early-onset retinal degeneration. <a href="#12" class="mim-tip-reference" title="Rachel, R. A., May-Simera, H. L., Veleri, S., Gotoh, N., Choi, B. Y., Murga-Zamalloa, C., McIntyre, J. C., Marek, J., Lopez, I., Hackett, A. N., Zhang, J., Brooks, M., and 12 others. <strong>Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.</strong> J. Clin. Invest. 122: 1233-1245, 2012. Note: Erratum: J. Clin. Invest. 122: 3025 only, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22446187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22446187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22446187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI60981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22446187">Rachel et al. (2012)</a> found that Cep290 and Mkks localized to adjacent regions in ciliated sensory cells in mice. Yeast 2-hybrid and coimmunoprecipitation analyses showed that full-length human MKKS interacted with the C-terminal domain of human CEP290 corresponding to the region deleted in rd16 mice, as well as with full-length CEP290. Some Bardet-Biedl syndrome (BBS; see <a href="/entry/605231">605231</a>)-associated MKKS mutants (e.g., G52D; <a href="#0005">604896.0005</a>) showed weak or nonexistent interaction with the CEP290 C-terminal domain in yeast 2-hybrid analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22446187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Scott, C. A., Marsden, A. N., Rebagliati, M. R., Zhang, Q., Chamling, X., Searby, C. C., Baye, L. M., Sheffield, V. C., Slusarski, D. C. <strong>Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein.</strong> PLoS Genet. 13: e1006936, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28753627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28753627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28753627[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.pgen.1006936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28753627">Scott et al. (2017)</a> used CRISPR/Cas9 to knockout Mkks in mouse medullary collecting duct cells and induced ciliation by serum starvation. They observed a reduced number of ciliated mutant cells compared with wildtype cells. Transfection of mutant cells with wildtype human MKKS or with the McKusick-Kaufman syndrome-associated MKKS(H84Y/A242S) allele rescued the ciliation defect. Using inhibitor studies in HEK293T cells, the authors showed that MKKS required active transport to overcome nuclear accumulation, as demonstrated by fluorescence microscopy and cell fractionation. Nuclear transport was disrupted in cells transfected with MKKS(H84Y/A242S), but not in cells transfected with wildtype MKKS or with the BBS-associated allele MKKS(Y37C). Using GFP-tagged MKKS protein, immunoprecipitation, and confocal microscopy, <a href="#14" class="mim-tip-reference" title="Scott, C. A., Marsden, A. N., Rebagliati, M. R., Zhang, Q., Chamling, X., Searby, C. C., Baye, L. M., Sheffield, V. C., Slusarski, D. C. <strong>Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein.</strong> PLoS Genet. 13: e1006936, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28753627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28753627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28753627[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.pgen.1006936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28753627">Scott et al. (2017)</a> identified SMARCC1 (<a href="/entry/601732">601732</a>) as a predominantly cytoplasmic interacting partner of MKKS in zebrafish and HEK293T cells. Knockout of MKKS in HEK293T cells resulted in decreased SMARCC1 expression in cytoplasm. MKKS overexpression enhanced SMARCC1 cytoplasmic expression. Transfection with MKKS(H84Y/A242S) resulted in increased cytoplasmic retention of SMARCC1 compared with wildtype MKKS. <a href="#14" class="mim-tip-reference" title="Scott, C. A., Marsden, A. N., Rebagliati, M. R., Zhang, Q., Chamling, X., Searby, C. C., Baye, L. M., Sheffield, V. C., Slusarski, D. C. <strong>Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein.</strong> PLoS Genet. 13: e1006936, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28753627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28753627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28753627[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.pgen.1006936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28753627">Scott et al. (2017)</a> proposed that MKKS has an important function in nuclear-cytoplasmic transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28753627" 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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In an Amish patient with McKusick-Kaufman syndrome (MKKS; <a href="/entry/236700">236700</a>), <a href="#19" class="mim-tip-reference" title="Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G. <strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong> Nature Genet. 25: 79-82, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802661</a>] [<a href="https://doi.org/10.1038/75637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802661">Stone et al. (2000)</a> identified homozygosity for 2 missense substitutions in cis in the MKKS gene (<a href="#0001">604896.0001</a>). In a non-Amish patient with MKKS, they identified compound heterozygous mutations in the MKKS gene: a frameshift mutation predicting premature protein termination (<a href="#0004">604896.0004</a>) and a missense mutation (<a href="#0003">604896.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802661" 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</em></strong></p><p>
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<a href="#17" class="mim-tip-reference" title="Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G. <strong>Mutations in MKKS cause Bardet-Biedl syndrome.</strong> Nature Genet. 26: 15-16, 2000. Note: Erratum: Nature Genet. 28: 193 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973238</a>] [<a href="https://doi.org/10.1038/79116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973238">Slavotinek et al. (2000)</a> and <a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a> identified a sixth form of Bardet-Biedl syndrome (BBS6; <a href="/entry/605231">605231</a>), which is due to mutations in the MKKS gene (see, e.g., <a href="#0007">604896.0007</a>). Bardet-Biedl syndrome is an autosomal recessive disorder predominantly characterized by obesity, retinal dystrophy, polydactyly, learning difficulties, hypogenitalism, and renal malformations, with secondary features that include diabetes mellitus, endocrinologic dysfunction, and behavioral abnormalities. <a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a> performed a genome screen in BBS families from Newfoundland in which linkage to known BBS loci had been excluded. Fine mapping reduced the critical interval to a region including the MKKS gene. Given the mapping position and the clinical similarity between McKusick-Kaufman syndrome and Bardet-Biedl syndrome, they screened the MKKS gene and identified mutations in 5 Newfoundland and 2 European-American BBS pedigrees. Most were frameshift mutations, predicted to result in a nonfunctional protein. The data suggested that a complete loss of function of the MKKS product, and thus an inability to fold a range of target proteins, leads to the clinical manifestations of BBS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10973251+10973238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G. <strong>Mutations in MKKS cause Bardet-Biedl syndrome.</strong> Nature Genet. 26: 15-16, 2000. Note: Erratum: Nature Genet. 28: 193 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973238</a>] [<a href="https://doi.org/10.1038/79116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973238">Slavotinek et al. (2000)</a> ascertained 34 unrelated probands with classic features of BBS including retinitis pigmentosa, obesity, and polydactyly. The probands were from families unsuitable for linkage because of family size. They found MKKS mutations in 4 typical BBS probands. Three of the probands were from Newfoundland and had been included in the study of <a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a>. <a href="#17" class="mim-tip-reference" title="Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G. <strong>Mutations in MKKS cause Bardet-Biedl syndrome.</strong> Nature Genet. 26: 15-16, 2000. Note: Erratum: Nature Genet. 28: 193 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973238</a>] [<a href="https://doi.org/10.1038/79116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973238">Slavotinek et al. (2000)</a> likewise suggested that the clinical features of BBS may be caused by the inability of the MKKS putative chaperonin to maintain protein integrity in the retina, brain, pancreas, and other organs. The results suggested that genes encoding chaperonins and their substrates are candidates for other BBS loci, retinitis pigmentosa, diabetes, obesity, and mental retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10973251+10973238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Beales, P. L., Katsanis, N., Lewis, R. A., Ansley, S. J., Elcioglu, N., Raza, J., Woods, M. O., Green, J. S., Parfrey, P. S., Davidson, W. S., Lupski, J. R. <strong>Genetic and mutational analyses of a large multiethnic Bardet-Biedl cohort reveal a minor involvement of BBS6 and delineate the critical intervals of other loci.</strong> Am. J. Hum. Genet. 68: 606-616, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 922 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179009</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179009[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/318794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11179009">Beales et al. (2001)</a> found mutations in MKKS in only 4 to 11% of unselected BBS patients. <a href="#16" class="mim-tip-reference" title="Slavotinek, A. M., Searby, C., Al-Gazali, L., Hennekam, R. C. M., Schrander-Stumpel, C., Orcana-Losa, M., Pardo-Reoyo, S., Cantani, A., Kumar, D., Capellini, Q., Neri, G., Zackai, E., Biesecker, L. G. <strong>Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients.</strong> Hum. Genet. 110: 561-567, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107442</a>] [<a href="https://doi.org/10.1007/s00439-002-0733-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12107442">Slavotinek et al. (2002)</a> hypothesized that an analysis of patients with atypical BBS and MKKS (group I; 15 probands) and patients with BBS who had linkage results inconsistent with linkage to other BBS loci (group II; 12 probands) could increase the MKKS mutation yield. Two mutant alleles in the MKKS gene were identified in only 2 families in group II. Single (heterozygous) sequence variations were found in 3 group I families and in 2 group II families. Combining these results with previously published data showed that only 1 mutant allele was detected in nearly half of all patients screened, suggesting that unusual mutational mechanisms or patterns of inheritance may have been involved. However, sequencing of the BBS2 gene (<a href="/entry/606151">606151</a>) in these patients did not provide any evidence of digenic triallelic inheritance. The frequency of detected mutations in MKKS in group II patients was 24%, i.e., 6 times higher than the published rate for unselected BBS patients, suggesting that small-scale linkage analyses may be useful in suitable families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11179009+12107442" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Karmous-Benailly, H., Martinovic, J., Gubler, M.-C., Sirot, Y., Clech, L., Ozilou, C., Auge, J., Brahimi, N., Etchevers, H., Detrait, E., Esculpavit, C., Audollent, S., and 17 others. <strong>Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel syndrome.</strong> Am. J. Hum. Genet. 76: 493-504, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15666242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15666242</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15666242[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/428679" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15666242">Karmous-Benailly et al. (2005)</a> sequenced the BBS6 gene and others of the 8 genes (BBS1-BBS8) that have been identified as mutant in BBS. They speculated that because of the clinical overlap in the features of BBS observed at birth (polydactyly, kidney anomalies, hepatic fibrosis, and genital and heart malformations) with those of Meckel syndrome (<a href="/entry/249000">249000</a>), some fetuses diagnosed as having Meckel or 'Meckel-like' syndrome (see <a href="/entry/208540">208540</a>) might have mutations in a BBS gene. Indeed, they found a recessive mutation in the BBS2 gene in 3 such fetuses, 2 in BBS4 (<a href="/entry/600374">600374</a>), and 1 in BBS6. They also found a heterozygous BBS6 mutation in 3 additional cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15666242" 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="Badano, J. L., Kim, J. C., Hoskins, B. E., Lewis, R. A., Ansley, S. J., Cutler, D. J., Castellan, C., Beales, P. L., Leroux, M. R., Katsanis, N. <strong>Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus.</strong> Hum. Molec. Genet. 12: 1651-1659, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837689</a>] [<a href="https://doi.org/10.1093/hmg/ddg188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12837689">Badano et al. (2003)</a> presented 3 families with 2 mutations in either the BBS1 gene or the BBS2 gene, in which some, but not all, patients carried a third mutation in the BBS1, BBS2, or BBS6 genes. In each example, the presence of 3 mutant alleles correlated with a more severe phenotype. The introduction in mammalian cells of 1 of the mutations in the BBS6 gene (<a href="#0014">604896.0014</a>) caused a dramatic mislocalization of the protein compared with the wildtype. <a href="#2" class="mim-tip-reference" title="Badano, J. L., Kim, J. C., Hoskins, B. E., Lewis, R. A., Ansley, S. J., Cutler, D. J., Castellan, C., Beales, P. L., Leroux, M. R., Katsanis, N. <strong>Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus.</strong> Hum. Molec. Genet. 12: 1651-1659, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837689</a>] [<a href="https://doi.org/10.1093/hmg/ddg188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12837689">Badano et al. (2003)</a> suggested that 3 mutant alleles are not always necessary for disease manifestation, but might potentiate a phenotype that is caused by 2 mutations at an independent locus, thus introducing an additional layer of complexity on the genetic modeling of oligogenicity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837689" 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 population-based study including 93 BBS patients from 74 families of various ethnicities, <a href="#4" class="mim-tip-reference" title="Billingsley, G., Bin, J., Fieggen, K. J., Duncan, J. L., Gerth, C., Ogata, K., Wodak, S. S., Traboulsi, E. I., Fishman, G. A., Paterson, A., Chitayat, D., Knueppel, T., Millan, J. M., Mitchell, G. A., Deveault, C., Heon, E. <strong>Mutations in chaperonin-like BBS genes are a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population.</strong> J. Med. Genet. 47: 453-463, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20472660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20472660</a>] [<a href="https://doi.org/10.1136/jmg.2009.073205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20472660">Billingsley et al. (2010)</a> determined that the chaperonin-like BBS6, BBS10 (<a href="/entry/610148">610148</a>), and BBS12 (<a href="/entry/610683">610683</a>) genes are a major contributor to the disorder. Biallelic mutations in these 3 genes were found in 36.5% of the families: 4 patients had mutations in BBS6, 19 had mutations in BBS10, and 10 had mutations in BBS12. Overall, 26 (68%) of 38 mutations were novel. Six patients had mutations present in more than 1 chaperonin-like BBS gene, and 1 patient with a very severe phenotype had 4 mutations in BBS10. The phenotypes observed were beyond the classic BBS phenotype and overlapped with characteristics of MKKS (<a href="/entry/236700">236700</a>), including congenital heart defect, vaginal atresia, hydrometrocolpos, and cryptorchidism, and with Alstrom syndrome (<a href="/entry/203800">203800</a>), including diabetes, hearing loss, liver abnormalities, endocrine anomalies, and cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20472660" 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>Associations Pending Confirmation</em></strong></p><p>
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To investigate whether variation in the MKKS gene contributes to common and probably polygenic forms of obesity, <a href="#1" class="mim-tip-reference" title="Andersen, K. L., Echwald, S. M., Larsen, L. H., Hamid, Y. H., Glumer, C., Jorgensen, T., Borch-Johnsen, K., Andersen, T., Sorensen, T. I. A., Hansen, T., Pedersen, O. <strong>Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity.</strong> J. Clin. Endocr. Metab. 90: 225-230, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15483080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15483080</a>] [<a href="https://doi.org/10.1210/jc.2004-0465" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15483080">Andersen et al. (2005)</a> performed mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. They identified 5 variants, including the rare ala242-to-ser mutation (see <a href="#0001">604896.0001</a>) in 2 families, where it showed partial cosegregation with obesity. Other variants failed to show an association. The authors concluded that it is unlikely that MKKS variants play a major role in the pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may contribute to obesity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15483080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For discussion of a possible association between variation in the MKKS gene and the metabolic syndrome, see AOMS1 (<a href="/entry/605552">605552</a>).</p>
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<p><a href="#5" class="mim-tip-reference" title="Fath, M. A., Mullins, R. F., Searby, C., Nishimura, D. Y., Wei, J., Rahmouni, K., Davis, R. E., Tayeh, M. K., Andrews, M., Yang, B., Sigmund, C. D., Stone, E. M., Sheffield, V. C. <strong>Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome.</strong> Hum. Molec. Genet. 14: 1109-1118, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772095</a>] [<a href="https://doi.org/10.1093/hmg/ddi123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15772095">Fath et al. (2005)</a> developed an Mkks -/- mouse model in which affected animals demonstrated retinal degeneration, failure of spermatozoa flagella formation, elevated blood pressure, olfactory deficits, and social dominance, but no polydactyly nor vaginal abnormalities. The phenotype of the Mkks -/- mice closely resembled the phenotype of other mouse models of Bardet-Biedl syndrome (Bbs2 -/- and Bbs4 -/-). <a href="#5" class="mim-tip-reference" title="Fath, M. A., Mullins, R. F., Searby, C., Nishimura, D. Y., Wei, J., Rahmouni, K., Davis, R. E., Tayeh, M. K., Andrews, M., Yang, B., Sigmund, C. D., Stone, E. M., Sheffield, V. C. <strong>Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome.</strong> Hum. Molec. Genet. 14: 1109-1118, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772095</a>] [<a href="https://doi.org/10.1093/hmg/ddi123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15772095">Fath et al. (2005)</a> suggested that the complete absence of the MKKS gene leads to BBS while the McKusick-Kaufman phenotype is likely to be due to specific mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15772095" 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="#18" class="mim-tip-reference" title="Stoetzel, C., Muller, J., Laurier, V., Davis, E. E., Zaghloul, N. A., Vicaire, S., Jacquelin, C., Plewniak, F., Leitch, C. C., Sarda, P., Hamel, C., de Ravel, T. J. L., and 10 others. <strong>Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome.</strong> Am. J. Hum. Genet. 80: 1-11, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17160889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17160889</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17160889[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/510256" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17160889">Stoetzel et al. (2007)</a> suppressed BBS6, BBS10, and BBS12 (<a href="/entry/610683">610683</a>) in zebrafish and observed gastrulation-movement defects characteristic of other BBS morphants. Suppression of each of these chaperonin-like molecules yielded highly overlapping phenotypes, but simultaneous suppression of these 3 genes, which comprise a subfamily, grossly exaggerated the penetrance and expressivity of these phenotypes. <a href="#18" class="mim-tip-reference" title="Stoetzel, C., Muller, J., Laurier, V., Davis, E. E., Zaghloul, N. A., Vicaire, S., Jacquelin, C., Plewniak, F., Leitch, C. C., Sarda, P., Hamel, C., de Ravel, T. J. L., and 10 others. <strong>Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome.</strong> Am. J. Hum. Genet. 80: 1-11, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17160889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17160889</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17160889[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/510256" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17160889">Stoetzel et al. (2007)</a> suggested that this effect might underlie either some partial functional redundancy within the subfamily or might reflect the progressive loss of pericentriolar function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17160889" 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 mice lacking Bbs2, Bbs4, or Bbs6 and mice with the met390-to-arg (M390R; <a href="/entry/209901#0001">209901.0001</a>) mutation in Bbs1 (<a href="/entry/209901">209901</a>), <a href="#15" class="mim-tip-reference" title="Shah, A. S., Farmen, S. L., Moninger, T. O., Businga, T. R., Andrews, M. P., Bugge, K., Searby, C. C., Nishimura, D., Brogden, K. A., Kline, J. N., Sheffield, V. C., Welsh, M. J. <strong>Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia.</strong> Proc. Nat. Acad. Sci. 105: 3380-3385, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18299575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18299575</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18299575[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0712327105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18299575">Shah et al. (2008)</a> showed that expression of BBS proteins was not required for ciliogenesis, but their loss caused structural defects in a fraction of cilia covering airway epithelia. The most common abnormality was bulges filled with vesicles near the tips of cilia, and this same misshapen appearance was present in airway cilia from all mutant mouse strains. Cilia of Bbs4-null and Bbs1 mutant mice beat at a lower frequency than wildtype cilia. Neither airway hyperresponsiveness nor inflammation increased in Bbs2- or Bbs4-null mice immunized with ovalbumin compared with wildtype mice. Instead, mutant animals were partially protected from airway hyperresponsiveness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18299575" 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="Rahmouni, K., Fath, M. A., Seo, S., Thedens, D. R., Berry, C. J., Weiss, R., Nishimura, D. Y., Sheffield, V. C. <strong>Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome.</strong> J. Clin. Invest. 118: 1458-1467, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18317593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18317593</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18317593[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI32357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18317593">Rahmouni et al. (2008)</a> studied Bbs2 -/-, Bbs4 -/-, and Bbs6 -/- mice and found that obesity was associated with hyperleptinemia (<a href="/entry/164160">164160</a>) and resistance to the anorectic and weight-reducing effects of leptin. Although all 3 of the BBS mouse models were similarly resistant to the metabolic actions of leptin, only Bbs4 -/- and Bbs6 -/- mice remained responsive to the effects of leptin on renal sympathetic nerve activity and arterial pressure and developed hypertension. The authors also found that BBS mice had decreased hypothalamic expression of proopiomelanocortin (POMC; <a href="/entry/176830">176830</a>), and suggested that BBS genes play an important role in maintaining leptin sensitivity in POMC neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18317593" 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>Mice homozygous for the rd16 truncation mutation in Cep290 develop early-onset retinal degeneration. <a href="#12" class="mim-tip-reference" title="Rachel, R. A., May-Simera, H. L., Veleri, S., Gotoh, N., Choi, B. Y., Murga-Zamalloa, C., McIntyre, J. C., Marek, J., Lopez, I., Hackett, A. N., Zhang, J., Brooks, M., and 12 others. <strong>Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.</strong> J. Clin. Invest. 122: 1233-1245, 2012. Note: Erratum: J. Clin. Invest. 122: 3025 only, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22446187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22446187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22446187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI60981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22446187">Rachel et al. (2012)</a> demonstrated that the rd16 mutation removes a domain of Cep290 that interacts with Mkks (see GENE FUNCTION). They found that haploinsufficiency of Mkks at least partly rescued ciliary pathology in some mice homozygous for the rd16 mutation. Likewise, haploinsufficiency of Cep290 partly rescued ciliary pathology in Mkks -/- mice. In contrast, haploinsufficiency of both proteins in zebrafish exacerbated ciliary defects found in single-mutant animals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22446187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Scott, C. A., Marsden, A. N., Rebagliati, M. R., Zhang, Q., Chamling, X., Searby, C. C., Baye, L. M., Sheffield, V. C., Slusarski, D. C. <strong>Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein.</strong> PLoS Genet. 13: e1006936, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28753627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28753627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28753627[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.pgen.1006936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28753627">Scott et al. (2017)</a> knocked down Bbs6 in zebrafish using 2 independent morpholino oligonucleotides and observed Kupffer vesicle (KV) cilia defects and delays in retrograde cellular transport, as seen with knockdown of other BBS genes. Fluorescent microscopy demonstrated a significant reduction of KV cilia length, but transfection with wildtype human MKKS or with the human McKusick-Kaufman syndrome-associated allele MKKS(H84Y/A242S) allowed for ciliogenesis and cilia maintenance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28753627" 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> rs74315394 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315394;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/rs74315394?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=rs74315394" 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=rs74315394" 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=RCV000005632 OR RCV000153503 OR RCV000436285 OR RCV000990285 OR RCV001084541 OR RCV001865699 OR RCV003476316 OR RCV004701653" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005632, RCV000153503, RCV000436285, RCV000990285, RCV001084541, RCV001865699, RCV003476316, RCV004701653" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005632...</a>
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<p>In an Old Order Amish patient with McKusick-Kaufman syndrome (MKKS; <a href="/entry/236700">236700</a>), <a href="#19" class="mim-tip-reference" title="Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G. <strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong> Nature Genet. 25: 79-82, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802661</a>] [<a href="https://doi.org/10.1038/75637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802661">Stone et al. (2000)</a> identified homozygosity for 2 mutations on the same allele in the MKKS gene. One was a 1137C-T transition, resulting in a his84-to-tyr (H84Y) substitution, and the other resulted in an ala242-to-ser (A242S) substitution. This allele, with both alterations, was found in 1 of 100 Amish 'control' chromosomes, which suggests a carrier frequency of approximately 2%, similar to the estimated carrier frequency calculated using the incidence of this disorder among the Amish. Neither Amish substitution was found in an additional 100 non-Amish control chromosomes. The H84Y mutation was predicted to interfere with ATP hydrolysis, which in other chaperonins leads to substantially reduced function. Three individuals homozygous for the affected chromosome had a normal phenotype, consistent with the incomplete penetrance of the MKKS phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802661" 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 follow-up study of the Amish family reported by <a href="#19" class="mim-tip-reference" title="Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G. <strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong> Nature Genet. 25: 79-82, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802661</a>] [<a href="https://doi.org/10.1038/75637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802661">Stone et al. (2000)</a> in which the unaffected mother was homozygous for the H84Y and A242S mutations, <a href="#11" class="mim-tip-reference" title="Nakane, T., Biesecker, L. G. <strong>No evidence for triallelic inheritance of MKKS/BBS loci in Amish McKusick-Kaufman syndrome.</strong> Am. J. Med. Genet. 138A: 32-34, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16104012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16104012</a>] [<a href="https://doi.org/10.1002/ajmg.a.30593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16104012">Nakane and Biesecker (2005)</a> excluded triallelic inheritance for multiple BBS genes (see, e.g., BBS1, <a href="/entry/209901">209901</a>) as an explanation for the incomplete penetrance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16104012+10802661" 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> rs74315396 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315396;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/rs74315396?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=rs74315396" 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=rs74315396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a sporadic non-Amish case of McKusick-Kaufman syndrome (MKKS; <a href="/entry/236700">236700</a>), <a href="#19" class="mim-tip-reference" title="Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G. <strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong> Nature Genet. 25: 79-82, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802661</a>] [<a href="https://doi.org/10.1038/75637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802661">Stone et al. (2000)</a> identified an A-to-G transition at nucleotide 997 of the MKKS gene, resulting in a tyrosine-to-cysteine substitution at codon 37 (Y37C). This mutation was not identified in over 200 chromosomes from a non-Amish control group. The patient was a compound heterozygote for a frameshift mutation (<a href="#0004">604896.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The same Y37C mutation was found in homozygous state in a pedigree with Bardet-Biedl syndrome-6 (BBS6; <a href="/entry/605231">605231</a>) (<a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Katsanis, N., Ansley, S. J., Badano, J. L., Eichers, E. R., Lewis, R. A., Hoskins, B. E., Scambler, P. J., Davidson, W. S., Beales, P. L., Lupski, J. R. <strong>Triallelic inheritance in Bardet-Biedl syndrome, a mendelian recessive disorder.</strong> Science 293: 2256-2259, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11567139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11567139</a>] [<a href="https://doi.org/10.1126/science.1063525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11567139">Katsanis et al. (2001)</a> reported an individual who was homozygous for the Y37C mutation and carried a third mutation, which they stated was an asn70-to-ser (N70S) substitution in the BBS2 gene; however, gnomAD (v2.1.1) lists serine as the reference allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11567139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MCKUSICK-KAUFMAN SYNDROME</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> rs1421664374 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1421664374;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/rs1421664374?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=rs1421664374" 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=rs1421664374" 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=RCV000005635 OR RCV003764529" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005635, RCV003764529" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005635...</a>
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<p>In a sporadic non-Amish case of McKusick-Kaufman syndrome (MKKS; <a href="/entry/236700">236700</a>), <a href="#19" class="mim-tip-reference" title="Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G. <strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong> Nature Genet. 25: 79-82, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802661</a>] [<a href="https://doi.org/10.1038/75637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802661">Stone et al. (2000)</a> identified a 2-bp deletion at nucleotide 2111 and 2112 of the MKKS gene, resulting in a frameshift leading to premature termination. This mutation was maternally inherited. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802661" 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> rs28937875 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937875;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/rs28937875?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=rs28937875" 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=rs28937875" 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=RCV000005636 OR RCV001851674 OR RCV002222342 OR RCV005025008" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005636, RCV001851674, RCV002222342, RCV005025008" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005636...</a>
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<p>In a patient with Bardet-Biedl syndrome-6 (BBS6; <a href="/entry/605231">605231</a>), a 13-year-old Hispanic girl with severe retinitis pigmentosa, postaxial polydactyly, mental retardation, and obesity, <a href="#17" class="mim-tip-reference" title="Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G. <strong>Mutations in MKKS cause Bardet-Biedl syndrome.</strong> Nature Genet. 26: 15-16, 2000. Note: Erratum: Nature Genet. 28: 193 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973238</a>] [<a href="https://doi.org/10.1038/79116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973238">Slavotinek et al. (2000)</a> found compound heterozygosity for a missense (1042G-A, gly52 to asp; G52D) and a nonsense (1679T-A, tyr264 to ter; Y264X) mutation in exon 3 of the MKKS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Rachel, R. A., May-Simera, H. L., Veleri, S., Gotoh, N., Choi, B. Y., Murga-Zamalloa, C., McIntyre, J. C., Marek, J., Lopez, I., Hackett, A. N., Zhang, J., Brooks, M., and 12 others. <strong>Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.</strong> J. Clin. Invest. 122: 1233-1245, 2012. Note: Erratum: J. Clin. Invest. 122: 3025 only, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22446187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22446187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22446187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI60981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22446187">Rachel et al. (2012)</a> showed that MKKS with the G52D mutation was unable to interact with the C-terminal domain of the centrosomal protein CEP290 (<a href="/entry/610142">610142</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22446187" 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 6</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> rs74315397 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315397;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/rs74315397?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=rs74315397" 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=rs74315397" 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=RCV000005637" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005637" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005637</a>
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<p>For discussion of the tyr264-to-ter (T264X) mutation in the MKKS gene that was found in compound heterozygous state in a patient with Bardet-Biedl syndrome-6 (BBS6; <a href="/entry/605231">605231</a>) by <a href="#17" class="mim-tip-reference" title="Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G. <strong>Mutations in MKKS cause Bardet-Biedl syndrome.</strong> Nature Genet. 26: 15-16, 2000. Note: Erratum: Nature Genet. 28: 193 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973238</a>] [<a href="https://doi.org/10.1038/79116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973238">Slavotinek et al. (2000)</a>, see <a href="#0005">604896.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973238" 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">rs587777827 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777827;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=rs587777827" 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=rs587777827" 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=RCV000005638 OR RCV005031393" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005638, RCV005031393" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005638...</a>
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<p><a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a> found that all affected individuals from 2 Newfoundland pedigrees (families NF-B3 and NF-B4) with Bardet-Biedl syndrome-6 (BBS6; <a href="/entry/605231">605231</a>) were homozygous for deletion of 280T of the MKKS gene, which resulted in a frameshift after amino acid phenylalanine-94, terminating the protein at amino acid 103. They found the same alteration in compound heterozygous state in 2 other patients (see <a href="#0008">604896.0008</a> and <a href="#0009">604896.0009</a>), and it segregated with a haplotype-inferred prediction of a common ancestral chromosome in the 4 pedigrees. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G. <strong>Mutations in MKKS cause Bardet-Biedl syndrome.</strong> Nature Genet. 26: 15-16, 2000. Note: Erratum: Nature Genet. 28: 193 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973238</a>] [<a href="https://doi.org/10.1038/79116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973238">Slavotinek et al. (2000)</a> had independently studied the same Newfoundland families (their families 3 and 4) and identified a homozygous 1167delT mutation in each. In an erratum, the authors stated that their numbering differed from that of <a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a> because they chose the 5-prime end of the sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF221993" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF221993</a>) as '1,' whereas <a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a> chose the A of the putative ATG. Moreover, they stated that according to nomenclature convention, the numbering should have been 1168delT and 281delT, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10973251+10973238" 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> rs74315398 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315398;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/rs74315398?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=rs74315398" 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=rs74315398" 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=RCV000005639 OR RCV000481638 OR RCV001267056 OR RCV001851675 OR RCV003230348 OR RCV003987313 OR RCV004532293 OR RCV005025009" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005639, RCV000481638, RCV001267056, RCV001851675, RCV003230348, RCV003987313, RCV004532293, RCV005025009" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005639...</a>
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<p>In a Newfoundland patient with Bardet-Biedl syndrome-6 (BBS6; <a href="/entry/605231">605231</a>), <a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a> found compound heterozygosity for 2 mutations in the MKKS gene: 280delT (<a href="#0007">604896.0007</a>) and a missense mutation, leu277 to pro (L277P). The same patient was reported by <a href="#10" class="mim-tip-reference" title="Moore, S. J., Green, J. S., Fan, Y., Bhogal, A. K., Dicks, E., Fernandez, B. A., Stefanelli, M., Murphy, C., Cramer, B. C., Dean, J. C. S., Beales, P. L., Katsanis, N., Bassett, A. S., Davidson, W. S., Parfrey, P. S. <strong>Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study.</strong> Am. J. Med. Genet. 132A: 352-360, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637713</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15637713[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/10.1002/ajmg.a.30406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15637713">Moore et al. (2005)</a> as having been clinically diagnosed with Laurence-Moon syndrome (<a href="/entry/245800">245800</a>). <a href="#10" class="mim-tip-reference" title="Moore, S. J., Green, J. S., Fan, Y., Bhogal, A. K., Dicks, E., Fernandez, B. A., Stefanelli, M., Murphy, C., Cramer, B. C., Dean, J. C. S., Beales, P. L., Katsanis, N., Bassett, A. S., Davidson, W. S., Parfrey, P. S. <strong>Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study.</strong> Am. J. Med. Genet. 132A: 352-360, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637713</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15637713[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/10.1002/ajmg.a.30406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15637713">Moore et al. (2005)</a> considered their identification of mutations in the MKKS gene in a patient with Laurence-Moon syndrome as supporting the notion that Bardet-Biedl syndrome and Laurence-Moon syndrome are the same disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10973251+15637713" 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">rs2122235362 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2122235362;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=rs2122235362" 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=rs2122235362" 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=RCV002244221 OR RCV002502052 OR RCV003221313" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002244221, RCV002502052, RCV003221313" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002244221...</a>
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<p>In 2 affected members of a Newfoundland family segregating Bardet-Biedl syndrome-6 (BBS6; <a href="/entry/605231">605231</a>), <a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a> detected homozygosity for a complex 429delCT/433delAG allele of the MKKS gene that resulted in a frameshift of the termination of the protein at amino acid 157. Cloning and sequencing of the PCR product from 1 subject indicated that both deletions were on the same strand, suggesting that this mutation arose through a complex mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an independent study of the same Newfoundland family (their family 2) segregating BBS6, <a href="#17" class="mim-tip-reference" title="Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G. <strong>Mutations in MKKS cause Bardet-Biedl syndrome.</strong> Nature Genet. 26: 15-16, 2000. Note: Erratum: Nature Genet. 28: 193 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973238</a>] [<a href="https://doi.org/10.1038/79116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973238">Slavotinek et al. (2000)</a> identified homozygosity for 2 deletions in the MKKS gene, which they designated 1316delC and 1324-1326delGTA, in exon 3 of the MKKS gene, predicting a frameshift. In an erratum, <a href="#17" class="mim-tip-reference" title="Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G. <strong>Mutations in MKKS cause Bardet-Biedl syndrome.</strong> Nature Genet. 26: 15-16, 2000. Note: Erratum: Nature Genet. 28: 193 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973238</a>] [<a href="https://doi.org/10.1038/79116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973238">Slavotinek et al. (2000)</a> attributed the discrepancy in the naming of this mutation to ambiguity in the nomenclature system and the absence of biologic data that could resolve the discrepancy. The parents in this family were related. The proband and her affected brother had retinitis pigmentosa, postaxial polydactyly, mild mental retardation, morbid obesity, lobulated kidneys with prominent calyces, and diabetes mellitus (diagnosed at ages 33 and 30, respectively). A deceased sister had similar phenotypic features (retinitis pigmentosa with blindness by age 13, BMI greater than 45, abnormal glucose tolerance test, an IQ of 64, vaginal atresia, and syndactyly of both feet). Both parents and the maternal grandfather were heterozygous for the deletions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973238" 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="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a> identified 2 affected members of another Newfoundland family with BBS6 who were compound heterozygous for this complex mutation and another frameshift mutation (<a href="#0007">604896.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973251" 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> rs74315399 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315399;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/rs74315399?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=rs74315399" 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=rs74315399" 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=RCV000005641 OR RCV000990288 OR RCV001376920 OR RCV002307354" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005641, RCV000990288, RCV001376920, RCV002307354" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005641...</a>
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<p>In a pedigree with Bardet-Biedl syndrome-6 (BBS6; <a href="/entry/605231">605231</a>), <a href="#9" class="mim-tip-reference" title="Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R. <strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong> Nature Genet. 26: 67-70, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>] [<a href="https://doi.org/10.1038/79201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973251">Katsanis et al. (2000)</a> found that 1 MKKS allele carried a thr57-to-ala (T57A) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Rachel, R. A., May-Simera, H. L., Veleri, S., Gotoh, N., Choi, B. Y., Murga-Zamalloa, C., McIntyre, J. C., Marek, J., Lopez, I., Hackett, A. N., Zhang, J., Brooks, M., and 12 others. <strong>Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.</strong> J. Clin. Invest. 122: 1233-1245, 2012. Note: Erratum: J. Clin. Invest. 122: 3025 only, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22446187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22446187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22446187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI60981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22446187">Rachel et al. (2012)</a> showed that MKKS with the T57A mutation exhibited reduced interaction with the C-terminal domain of the centrosomal protein CEP290 (<a href="/entry/610142">610142</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22446187" 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">rs137853154 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853154;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=rs137853154" 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=rs137853154" 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=RCV000005643" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005643" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005643</a>
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<p>In a patient carrying 2 different termination codons in the BBS2 gene (<a href="/entry/606151#0003">606151.0003</a>, <a href="/entry/606151#0004">606151.0004</a>), <a href="#8" class="mim-tip-reference" title="Katsanis, N., Ansley, S. J., Badano, J. L., Eichers, E. R., Lewis, R. A., Hoskins, B. E., Scambler, P. J., Davidson, W. S., Beales, P. L., Lupski, J. R. <strong>Triallelic inheritance in Bardet-Biedl syndrome, a mendelian recessive disorder.</strong> Science 293: 2256-2259, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11567139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11567139</a>] [<a href="https://doi.org/10.1126/science.1063525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11567139">Katsanis et al. (2001)</a> identified a nonsense mutation in the BBS6 gene, a glutamine-to-termination substitution at codon 147. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11567139" 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">rs281797259 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281797259;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=rs281797259" 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=rs281797259" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient who was compound heterozygous for 2 nonsense mutations in the BBS2 gene, a leu168 frameshift, leading to a termination codon at residue 170 (<a href="/entry/606151#0014">606151.0014</a>), and an arg216-to-ter mutation (<a href="/entry/606151#0016">606151.0016</a>), <a href="#8" class="mim-tip-reference" title="Katsanis, N., Ansley, S. J., Badano, J. L., Eichers, E. R., Lewis, R. A., Hoskins, B. E., Scambler, P. J., Davidson, W. S., Beales, P. L., Lupski, J. R. <strong>Triallelic inheritance in Bardet-Biedl syndrome, a mendelian recessive disorder.</strong> Science 293: 2256-2259, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11567139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11567139</a>] [<a href="https://doi.org/10.1126/science.1063525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11567139">Katsanis et al. (2001)</a> identified a third mutation in the MKKS gene, a cysteine-to-serine substitution at codon 499. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11567139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Rachel, R. A., May-Simera, H. L., Veleri, S., Gotoh, N., Choi, B. Y., Murga-Zamalloa, C., McIntyre, J. C., Marek, J., Lopez, I., Hackett, A. N., Zhang, J., Brooks, M., and 12 others. <strong>Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.</strong> J. Clin. Invest. 122: 1233-1245, 2012. Note: Erratum: J. Clin. Invest. 122: 3025 only, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22446187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22446187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22446187[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI60981" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22446187">Rachel et al. (2012)</a> showed that MKKS with the C499S mutation exhibited reduced interaction with the C-terminal domain of the centrosomal protein CEP290 (<a href="/entry/610142">610142</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22446187" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0014 BARDET-BIEDL SYNDROME 1, MODIFIER OF</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">rs137853156 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853156;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=rs137853156" 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=rs137853156" 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=RCV000005645" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005645" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005645</a>
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<p>In 1 of 2 sisters with BBS1 (<a href="/entry/209900">209900</a>), <a href="#2" class="mim-tip-reference" title="Badano, J. L., Kim, J. C., Hoskins, B. E., Lewis, R. A., Ansley, S. J., Cutler, D. J., Castellan, C., Beales, P. L., Leroux, M. R., Katsanis, N. <strong>Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus.</strong> Hum. Molec. Genet. 12: 1651-1659, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837689</a>] [<a href="https://doi.org/10.1093/hmg/ddg188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12837689">Badano et al. (2003)</a> identified a 973A-C transversion in exon 3 of the MKKS gene, resulting in a thr325-to-pro (T325P) substitution which altered the 3-dimensional protein structure. Both sisters were compound heterozygous for mutations in the BBS1 gene: met390-to-arg (M390R; <a href="/entry/209901#0001">209901.0001</a>) and a 1-bp deletion (1650delC; <a href="/entry/209901#0008">209901.0008</a>). The sister with the T325P mutation was more severely affected than the sister without the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837689" 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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Andersen, K. L., Echwald, S. M., Larsen, L. H., Hamid, Y. H., Glumer, C., Jorgensen, T., Borch-Johnsen, K., Andersen, T., Sorensen, T. I. A., Hansen, T., Pedersen, O.
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<strong>Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity.</strong>
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J. Clin. Endocr. Metab. 90: 225-230, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15483080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15483080</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15483080" 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/10.1210/jc.2004-0465" target="_blank">Full Text</a>]
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Badano, J. L., Kim, J. C., Hoskins, B. E., Lewis, R. A., Ansley, S. J., Cutler, D. J., Castellan, C., Beales, P. L., Leroux, M. R., Katsanis, N.
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<strong>Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus.</strong>
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Hum. Molec. Genet. 12: 1651-1659, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837689</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837689" 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/ddg188" target="_blank">Full Text</a>]
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Beales, P. L., Katsanis, N., Lewis, R. A., Ansley, S. J., Elcioglu, N., Raza, J., Woods, M. O., Green, J. S., Parfrey, P. S., Davidson, W. S., Lupski, J. R.
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<strong>Genetic and mutational analyses of a large multiethnic Bardet-Biedl cohort reveal a minor involvement of BBS6 and delineate the critical intervals of other loci.</strong>
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Am. J. Hum. Genet. 68: 606-616, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 922 only, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11179009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11179009</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11179009[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=11179009" 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/10.1086/318794" target="_blank">Full Text</a>]
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</p>
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<p class="mim-text-font">
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<strong>Mutations in chaperonin-like BBS genes are a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population.</strong>
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[<a href="https://doi.org/10.1136/jmg.2009.073205" target="_blank">Full Text</a>]
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</p>
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<p class="mim-text-font">
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<strong>Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome.</strong>
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[<a href="https://doi.org/10.1093/hmg/ddi123" target="_blank">Full Text</a>]
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</p>
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<p class="mim-text-font">
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<strong>MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination.</strong>
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Molec. Biol. Cell 19: 899-911, 2008.
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[<a href="https://doi.org/10.1091/mbc.e07-07-0631" target="_blank">Full Text</a>]
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<p class="mim-text-font">
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<strong>Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15666242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15666242</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15666242[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=15666242" 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/10.1086/428679" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.1063525" target="_blank">Full Text</a>]
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<strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973251</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973251" 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/10.1038/79201" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30406" target="_blank">Full Text</a>]
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<strong>No evidence for triallelic inheritance of MKKS/BBS loci in Amish McKusick-Kaufman syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16104012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16104012</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16104012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30593" target="_blank">Full Text</a>]
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Rachel, R. A., May-Simera, H. L., Veleri, S., Gotoh, N., Choi, B. Y., Murga-Zamalloa, C., McIntyre, J. C., Marek, J., Lopez, I., Hackett, A. N., Zhang, J., Brooks, M., and 12 others.
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<strong>Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22446187/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22446187</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22446187[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=22446187" 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/10.1172/JCI60981" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18317593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18317593</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18317593[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=18317593" 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/10.1172/JCI32357" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1371/journal.pgen.1006936" target="_blank">Full Text</a>]
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Shah, A. S., Farmen, S. L., Moninger, T. O., Businga, T. R., Andrews, M. P., Bugge, K., Searby, C. C., Nishimura, D., Brogden, K. A., Kline, J. N., Sheffield, V. C., Welsh, M. J.
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[<a href="https://doi.org/10.1073/pnas.0712327105" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s00439-002-0733-3" target="_blank">Full Text</a>]
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<a id="Slavotinek2000" class="mim-anchor"></a>
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Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G.
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[<a href="https://doi.org/10.1038/79116" target="_blank">Full Text</a>]
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<a id="Stoetzel2007" class="mim-anchor"></a>
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Stoetzel, C., Muller, J., Laurier, V., Davis, E. E., Zaghloul, N. A., Vicaire, S., Jacquelin, C., Plewniak, F., Leitch, C. C., Sarda, P., Hamel, C., de Ravel, T. J. L., and 10 others.
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<strong>Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome.</strong>
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Am. J. Hum. Genet. 80: 1-11, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17160889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17160889</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17160889[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=17160889" 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/10.1086/510256" target="_blank">Full Text</a>]
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<a id="Stone2000" class="mim-anchor"></a>
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<p class="mim-text-font">
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Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G.
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<strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong>
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Nature Genet. 25: 79-82, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802661" 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/10.1038/75637" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 02/12/2018
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Paul J. Converse - updated : 12/13/2017<br>Marla J. F. O'Neill - updated : 12/29/2009<br>Marla J. F. O'Neill - updated : 7/22/2008<br>Patricia A. Hartz - updated : 7/22/2008<br>Patricia A. Hartz - updated : 5/21/2008<br>George E. Tiller - updated : 5/19/2008<br>John A. Phillips, III - updated : 4/10/2006<br>Cassandra L. Kniffin - updated : 9/22/2005<br>George E. Tiller - updated : 5/24/2005<br>Victor A. McKusick - updated : 2/9/2005<br>Victor A. McKusick - updated : 8/13/2002<br>Ada Hamosh - updated : 10/3/2001<br>Victor A. McKusick - updated : 8/24/2000
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Creation Date:
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Ada Hamosh : 4/29/2000
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carol : 09/20/2024
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carol : 04/11/2023<br>carol : 09/22/2022<br>alopez : 09/21/2022<br>carol : 08/25/2020<br>alopez : 11/07/2018<br>mgross : 02/12/2018<br>mgross : 12/15/2017<br>mgross : 12/13/2017<br>alopez : 07/23/2015<br>alopez : 10/23/2014<br>ckniffin : 10/21/2014<br>alopez : 10/16/2014<br>carol : 6/24/2014<br>terry : 3/14/2013<br>carol : 11/28/2012<br>wwang : 1/20/2010<br>terry : 12/29/2009<br>wwang : 4/20/2009<br>wwang : 7/23/2008<br>terry : 7/22/2008<br>wwang : 7/22/2008<br>terry : 7/22/2008<br>mgross : 5/21/2008<br>wwang : 5/20/2008<br>terry : 5/19/2008<br>carol : 5/6/2008<br>alopez : 11/1/2006<br>alopez : 4/10/2006<br>carol : 10/5/2005<br>wwang : 10/3/2005<br>ckniffin : 9/22/2005<br>tkritzer : 5/24/2005<br>carol : 5/23/2005<br>alopez : 2/22/2005<br>terry : 2/9/2005<br>carol : 8/19/2004<br>terry : 3/24/2004<br>tkritzer : 8/19/2002<br>tkritzer : 8/16/2002<br>tkritzer : 8/16/2002<br>terry : 8/13/2002<br>alopez : 7/18/2002<br>ckniffin : 5/14/2002<br>terry : 2/8/2002<br>alopez : 10/5/2001<br>alopez : 10/5/2001<br>terry : 10/3/2001<br>alopez : 8/28/2000<br>terry : 8/24/2000<br>alopez : 5/4/2000<br>alopez : 4/29/2000
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<span class="mim-font">
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<strong>*</strong> 604896
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<h3>
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MKKS CENTROSOMAL SHUTTLING PROTEIN; MKKS
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MKKS GENE<br />
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MKS<br />
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BBS6 GENE; BBS6
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<strong><em>HGNC Approved Gene Symbol: MKKS</em></strong>
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<strong>SNOMEDCT:</strong> 702407009;
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Cytogenetic location: 20p12.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 20:10,401,009-10,434,222 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Inheritance
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20p12.2
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Bardet-Biedl syndrome 6
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605231
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Autosomal recessive
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3
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McKusick-Kaufman syndrome
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<span class="mim-font">
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236700
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Cloning and Expression</strong>
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<p>Stone et al. (2000) analyzed the approximately 450-kb critical region on chromosome 20p12 for McKusick-Kaufman syndrome (MKKS; 236700) by sample sequencing, which revealed the presence of several known genes and EST clusters. Candidate transcripts were evaluated by Northern blot analysis of adult and fetal tissues. They selected 1 transcript with widespread expression for analysis in a patient from an Amish pedigree and a sporadic, non-Amish case. The Old Order Amish patient was found to be homozygous for an allele that had 2 missense substitutions, and the non-Amish patient was compound heterozygous for a frameshift mutation predicting premature protein truncation and a distinct missense mutation. The MKKS transcript has a predicted open reading frame of 570 amino acids Northern blot analysis revealed broad expression of a 2.4-kb transcript in human adult and fetal tissues. The MKKS predicted protein showed amino acid similarity to the chaperonin family of proteins (see 118190), suggesting a role for protein processing in limb, cardiac, and reproductive system development. Its closest protein relative is the alpha subunit of the Thermoplasma acidophilum thermosome. </p>
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<strong>Gene Structure</strong>
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<span class="mim-text-font">
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<p>Stone et al. (2000) determined that the MKKS gene has 6 exons with a start codon in exon 3 and 2 alternative 5-prime terminal exons that are noncoding. </p>
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<strong>Biochemical Features</strong>
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<p><strong><em>Crystal Structure</em></strong></p><p>
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Stone et al. (2000) modeled the 3-dimensional structure of the MKKS protein using data from the x-ray crystal structure of the T. acidophilum group II chaperonin protein. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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<span class="mim-text-font">
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<p>Using live cell imaging techniques, Hirayama et al. (2008) observed that MKKS was highly mobile and rapidly shuttled between the cytosol and centrosome. Several disease-associated mutations altered the degradation and/or solubility of the MKKS protein. The mutations T57A (604896.0010), C499S (604896.0013), and Y37C (604896.0003) caused both increased MKKS degradation and reduced solubility relative to wildtype MKKS, and the H84Y (604896.0001), whereas the A242S, R155L, and G345E mutations increased MKKS degradation only. Proteasome inhibition resulted in aggregation of the G345E mutant at the centrosome; however, the Y37C mutant was immobilized at the centrosome even in the absence of proteasome inhibition. The G345E and Y37C mutants were also highly polyubiquitinated, and immunoprecipitation analysis revealed that the rapidly degraded G345E mutant was recognized by components of the ubiquitin-proteasome protein degradation pathway, HSP70 (see HSPA1A; 140550), HSC70 (HSPA8; 600816), HSP90 (see HSPCA; 140571), and CHIP (STUB1; 607207). Knockdown of CHIP by RNA interference reduced the polyubiquitination and degradation of the G345E mutant protein. Hirayama et al. (2008) concluded that CHIP activity modulates the aggregation and stability of some MKKS mutant proteins. </p><p>Mice homozygous for the rd16 truncation mutation in the centrosomal protein Cep290 (610142) develop early-onset retinal degeneration. Rachel et al. (2012) found that Cep290 and Mkks localized to adjacent regions in ciliated sensory cells in mice. Yeast 2-hybrid and coimmunoprecipitation analyses showed that full-length human MKKS interacted with the C-terminal domain of human CEP290 corresponding to the region deleted in rd16 mice, as well as with full-length CEP290. Some Bardet-Biedl syndrome (BBS; see 605231)-associated MKKS mutants (e.g., G52D; 604896.0005) showed weak or nonexistent interaction with the CEP290 C-terminal domain in yeast 2-hybrid analysis. </p><p>Scott et al. (2017) used CRISPR/Cas9 to knockout Mkks in mouse medullary collecting duct cells and induced ciliation by serum starvation. They observed a reduced number of ciliated mutant cells compared with wildtype cells. Transfection of mutant cells with wildtype human MKKS or with the McKusick-Kaufman syndrome-associated MKKS(H84Y/A242S) allele rescued the ciliation defect. Using inhibitor studies in HEK293T cells, the authors showed that MKKS required active transport to overcome nuclear accumulation, as demonstrated by fluorescence microscopy and cell fractionation. Nuclear transport was disrupted in cells transfected with MKKS(H84Y/A242S), but not in cells transfected with wildtype MKKS or with the BBS-associated allele MKKS(Y37C). Using GFP-tagged MKKS protein, immunoprecipitation, and confocal microscopy, Scott et al. (2017) identified SMARCC1 (601732) as a predominantly cytoplasmic interacting partner of MKKS in zebrafish and HEK293T cells. Knockout of MKKS in HEK293T cells resulted in decreased SMARCC1 expression in cytoplasm. MKKS overexpression enhanced SMARCC1 cytoplasmic expression. Transfection with MKKS(H84Y/A242S) resulted in increased cytoplasmic retention of SMARCC1 compared with wildtype MKKS. Scott et al. (2017) proposed that MKKS has an important function in nuclear-cytoplasmic transport. </p>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>McKusick-Kaufman Syndrome</em></strong></p><p>
|
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In an Amish patient with McKusick-Kaufman syndrome (MKKS; 236700), Stone et al. (2000) identified homozygosity for 2 missense substitutions in cis in the MKKS gene (604896.0001). In a non-Amish patient with MKKS, they identified compound heterozygous mutations in the MKKS gene: a frameshift mutation predicting premature protein termination (604896.0004) and a missense mutation (604896.0003). </p><p><strong><em>Bardet-Biedl Syndrome</em></strong></p><p>
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Slavotinek et al. (2000) and Katsanis et al. (2000) identified a sixth form of Bardet-Biedl syndrome (BBS6; 605231), which is due to mutations in the MKKS gene (see, e.g., 604896.0007). Bardet-Biedl syndrome is an autosomal recessive disorder predominantly characterized by obesity, retinal dystrophy, polydactyly, learning difficulties, hypogenitalism, and renal malformations, with secondary features that include diabetes mellitus, endocrinologic dysfunction, and behavioral abnormalities. Katsanis et al. (2000) performed a genome screen in BBS families from Newfoundland in which linkage to known BBS loci had been excluded. Fine mapping reduced the critical interval to a region including the MKKS gene. Given the mapping position and the clinical similarity between McKusick-Kaufman syndrome and Bardet-Biedl syndrome, they screened the MKKS gene and identified mutations in 5 Newfoundland and 2 European-American BBS pedigrees. Most were frameshift mutations, predicted to result in a nonfunctional protein. The data suggested that a complete loss of function of the MKKS product, and thus an inability to fold a range of target proteins, leads to the clinical manifestations of BBS. </p><p>Slavotinek et al. (2000) ascertained 34 unrelated probands with classic features of BBS including retinitis pigmentosa, obesity, and polydactyly. The probands were from families unsuitable for linkage because of family size. They found MKKS mutations in 4 typical BBS probands. Three of the probands were from Newfoundland and had been included in the study of Katsanis et al. (2000). Slavotinek et al. (2000) likewise suggested that the clinical features of BBS may be caused by the inability of the MKKS putative chaperonin to maintain protein integrity in the retina, brain, pancreas, and other organs. The results suggested that genes encoding chaperonins and their substrates are candidates for other BBS loci, retinitis pigmentosa, diabetes, obesity, and mental retardation. </p><p>Beales et al. (2001) found mutations in MKKS in only 4 to 11% of unselected BBS patients. Slavotinek et al. (2002) hypothesized that an analysis of patients with atypical BBS and MKKS (group I; 15 probands) and patients with BBS who had linkage results inconsistent with linkage to other BBS loci (group II; 12 probands) could increase the MKKS mutation yield. Two mutant alleles in the MKKS gene were identified in only 2 families in group II. Single (heterozygous) sequence variations were found in 3 group I families and in 2 group II families. Combining these results with previously published data showed that only 1 mutant allele was detected in nearly half of all patients screened, suggesting that unusual mutational mechanisms or patterns of inheritance may have been involved. However, sequencing of the BBS2 gene (606151) in these patients did not provide any evidence of digenic triallelic inheritance. The frequency of detected mutations in MKKS in group II patients was 24%, i.e., 6 times higher than the published rate for unselected BBS patients, suggesting that small-scale linkage analyses may be useful in suitable families. </p><p>Karmous-Benailly et al. (2005) sequenced the BBS6 gene and others of the 8 genes (BBS1-BBS8) that have been identified as mutant in BBS. They speculated that because of the clinical overlap in the features of BBS observed at birth (polydactyly, kidney anomalies, hepatic fibrosis, and genital and heart malformations) with those of Meckel syndrome (249000), some fetuses diagnosed as having Meckel or 'Meckel-like' syndrome (see 208540) might have mutations in a BBS gene. Indeed, they found a recessive mutation in the BBS2 gene in 3 such fetuses, 2 in BBS4 (600374), and 1 in BBS6. They also found a heterozygous BBS6 mutation in 3 additional cases. </p><p>Badano et al. (2003) presented 3 families with 2 mutations in either the BBS1 gene or the BBS2 gene, in which some, but not all, patients carried a third mutation in the BBS1, BBS2, or BBS6 genes. In each example, the presence of 3 mutant alleles correlated with a more severe phenotype. The introduction in mammalian cells of 1 of the mutations in the BBS6 gene (604896.0014) caused a dramatic mislocalization of the protein compared with the wildtype. Badano et al. (2003) suggested that 3 mutant alleles are not always necessary for disease manifestation, but might potentiate a phenotype that is caused by 2 mutations at an independent locus, thus introducing an additional layer of complexity on the genetic modeling of oligogenicity. </p><p>In a population-based study including 93 BBS patients from 74 families of various ethnicities, Billingsley et al. (2010) determined that the chaperonin-like BBS6, BBS10 (610148), and BBS12 (610683) genes are a major contributor to the disorder. Biallelic mutations in these 3 genes were found in 36.5% of the families: 4 patients had mutations in BBS6, 19 had mutations in BBS10, and 10 had mutations in BBS12. Overall, 26 (68%) of 38 mutations were novel. Six patients had mutations present in more than 1 chaperonin-like BBS gene, and 1 patient with a very severe phenotype had 4 mutations in BBS10. The phenotypes observed were beyond the classic BBS phenotype and overlapped with characteristics of MKKS (236700), including congenital heart defect, vaginal atresia, hydrometrocolpos, and cryptorchidism, and with Alstrom syndrome (203800), including diabetes, hearing loss, liver abnormalities, endocrine anomalies, and cardiomyopathy. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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To investigate whether variation in the MKKS gene contributes to common and probably polygenic forms of obesity, Andersen et al. (2005) performed mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. They identified 5 variants, including the rare ala242-to-ser mutation (see 604896.0001) in 2 families, where it showed partial cosegregation with obesity. Other variants failed to show an association. The authors concluded that it is unlikely that MKKS variants play a major role in the pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may contribute to obesity. </p><p>For discussion of a possible association between variation in the MKKS gene and the metabolic syndrome, see AOMS1 (605552).</p>
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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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</h4>
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<span class="mim-text-font">
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<p>Fath et al. (2005) developed an Mkks -/- mouse model in which affected animals demonstrated retinal degeneration, failure of spermatozoa flagella formation, elevated blood pressure, olfactory deficits, and social dominance, but no polydactyly nor vaginal abnormalities. The phenotype of the Mkks -/- mice closely resembled the phenotype of other mouse models of Bardet-Biedl syndrome (Bbs2 -/- and Bbs4 -/-). Fath et al. (2005) suggested that the complete absence of the MKKS gene leads to BBS while the McKusick-Kaufman phenotype is likely to be due to specific mutations. </p><p>Stoetzel et al. (2007) suppressed BBS6, BBS10, and BBS12 (610683) in zebrafish and observed gastrulation-movement defects characteristic of other BBS morphants. Suppression of each of these chaperonin-like molecules yielded highly overlapping phenotypes, but simultaneous suppression of these 3 genes, which comprise a subfamily, grossly exaggerated the penetrance and expressivity of these phenotypes. Stoetzel et al. (2007) suggested that this effect might underlie either some partial functional redundancy within the subfamily or might reflect the progressive loss of pericentriolar function. </p><p>Using mice lacking Bbs2, Bbs4, or Bbs6 and mice with the met390-to-arg (M390R; 209901.0001) mutation in Bbs1 (209901), Shah et al. (2008) showed that expression of BBS proteins was not required for ciliogenesis, but their loss caused structural defects in a fraction of cilia covering airway epithelia. The most common abnormality was bulges filled with vesicles near the tips of cilia, and this same misshapen appearance was present in airway cilia from all mutant mouse strains. Cilia of Bbs4-null and Bbs1 mutant mice beat at a lower frequency than wildtype cilia. Neither airway hyperresponsiveness nor inflammation increased in Bbs2- or Bbs4-null mice immunized with ovalbumin compared with wildtype mice. Instead, mutant animals were partially protected from airway hyperresponsiveness. </p><p>Rahmouni et al. (2008) studied Bbs2 -/-, Bbs4 -/-, and Bbs6 -/- mice and found that obesity was associated with hyperleptinemia (164160) and resistance to the anorectic and weight-reducing effects of leptin. Although all 3 of the BBS mouse models were similarly resistant to the metabolic actions of leptin, only Bbs4 -/- and Bbs6 -/- mice remained responsive to the effects of leptin on renal sympathetic nerve activity and arterial pressure and developed hypertension. The authors also found that BBS mice had decreased hypothalamic expression of proopiomelanocortin (POMC; 176830), and suggested that BBS genes play an important role in maintaining leptin sensitivity in POMC neurons. </p><p>Mice homozygous for the rd16 truncation mutation in Cep290 develop early-onset retinal degeneration. Rachel et al. (2012) demonstrated that the rd16 mutation removes a domain of Cep290 that interacts with Mkks (see GENE FUNCTION). They found that haploinsufficiency of Mkks at least partly rescued ciliary pathology in some mice homozygous for the rd16 mutation. Likewise, haploinsufficiency of Cep290 partly rescued ciliary pathology in Mkks -/- mice. In contrast, haploinsufficiency of both proteins in zebrafish exacerbated ciliary defects found in single-mutant animals. </p><p>Scott et al. (2017) knocked down Bbs6 in zebrafish using 2 independent morpholino oligonucleotides and observed Kupffer vesicle (KV) cilia defects and delays in retrograde cellular transport, as seen with knockdown of other BBS genes. Fluorescent microscopy demonstrated a significant reduction of KV cilia length, but transfection with wildtype human MKKS or with the human McKusick-Kaufman syndrome-associated allele MKKS(H84Y/A242S) allowed for ciliogenesis and cilia maintenance. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>14 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MCKUSICK-KAUFMAN SYNDROME</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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MKKS, HIS84TYR AND ALA242SER
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<br />
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SNP: rs74315394,
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gnomAD: rs74315394,
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ClinVar: RCV000005632, RCV000153503, RCV000436285, RCV000990285, RCV001084541, RCV001865699, RCV003476316, RCV004701653
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</span>
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<span class="mim-text-font">
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<p>In an Old Order Amish patient with McKusick-Kaufman syndrome (MKKS; 236700), Stone et al. (2000) identified homozygosity for 2 mutations on the same allele in the MKKS gene. One was a 1137C-T transition, resulting in a his84-to-tyr (H84Y) substitution, and the other resulted in an ala242-to-ser (A242S) substitution. This allele, with both alterations, was found in 1 of 100 Amish 'control' chromosomes, which suggests a carrier frequency of approximately 2%, similar to the estimated carrier frequency calculated using the incidence of this disorder among the Amish. Neither Amish substitution was found in an additional 100 non-Amish control chromosomes. The H84Y mutation was predicted to interfere with ATP hydrolysis, which in other chaperonins leads to substantially reduced function. Three individuals homozygous for the affected chromosome had a normal phenotype, consistent with the incomplete penetrance of the MKKS phenotype. </p><p>In a follow-up study of the Amish family reported by Stone et al. (2000) in which the unaffected mother was homozygous for the H84Y and A242S mutations, Nakane and Biesecker (2005) excluded triallelic inheritance for multiple BBS genes (see, e.g., BBS1, 209901) as an explanation for the incomplete penetrance. </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-text-font">
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<strong>.0002 MOVED TO 604896.0001</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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<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>.0003 MCKUSICK-KAUFMAN SYNDROME</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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BARDET-BIEDL SYNDROME 6, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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MKKS, TYR37CYS
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<br />
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SNP: rs74315396,
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gnomAD: rs74315396,
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ClinVar: RCV000005633, RCV000005634, RCV000724561, RCV000763444, RCV000824067, RCV001075509, RCV001267323, RCV001328206, RCV002222341, RCV004532292
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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 sporadic non-Amish case of McKusick-Kaufman syndrome (MKKS; 236700), Stone et al. (2000) identified an A-to-G transition at nucleotide 997 of the MKKS gene, resulting in a tyrosine-to-cysteine substitution at codon 37 (Y37C). This mutation was not identified in over 200 chromosomes from a non-Amish control group. The patient was a compound heterozygote for a frameshift mutation (604896.0004). </p><p>The same Y37C mutation was found in homozygous state in a pedigree with Bardet-Biedl syndrome-6 (BBS6; 605231) (Katsanis et al., 2000). </p><p>Katsanis et al. (2001) reported an individual who was homozygous for the Y37C mutation and carried a third mutation, which they stated was an asn70-to-ser (N70S) substitution in the BBS2 gene; however, gnomAD (v2.1.1) lists serine as the reference allele. </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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<h4>
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<span class="mim-font">
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<strong>.0004 MCKUSICK-KAUFMAN SYNDROME</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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MKKS, 2-BP DEL, 2111GG
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<br />
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SNP: rs1421664374,
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gnomAD: rs1421664374,
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ClinVar: RCV000005635, RCV003764529
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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 sporadic non-Amish case of McKusick-Kaufman syndrome (MKKS; 236700), Stone et al. (2000) identified a 2-bp deletion at nucleotide 2111 and 2112 of the MKKS gene, resulting in a frameshift leading to premature termination. This mutation was maternally inherited. </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 BARDET-BIEDL SYNDROME 6</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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MKKS, GLY52ASP
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<br />
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SNP: rs28937875,
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gnomAD: rs28937875,
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ClinVar: RCV000005636, RCV001851674, RCV002222342, RCV005025008
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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 patient with Bardet-Biedl syndrome-6 (BBS6; 605231), a 13-year-old Hispanic girl with severe retinitis pigmentosa, postaxial polydactyly, mental retardation, and obesity, Slavotinek et al. (2000) found compound heterozygosity for a missense (1042G-A, gly52 to asp; G52D) and a nonsense (1679T-A, tyr264 to ter; Y264X) mutation in exon 3 of the MKKS gene. </p><p>Rachel et al. (2012) showed that MKKS with the G52D mutation was unable to interact with the C-terminal domain of the centrosomal protein CEP290 (610142). </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 6</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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MKKS, TYR264TER
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<br />
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SNP: rs74315397,
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gnomAD: rs74315397,
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ClinVar: RCV000005637
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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 tyr264-to-ter (T264X) mutation in the MKKS gene that was found in compound heterozygous state in a patient with Bardet-Biedl syndrome-6 (BBS6; 605231) by Slavotinek et al. (2000), see 604896.0005. </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 6</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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MKKS, 1-BP DEL, 281T
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<br />
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SNP: rs587777827,
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ClinVar: RCV000005638, RCV005031393
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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>Katsanis et al. (2000) found that all affected individuals from 2 Newfoundland pedigrees (families NF-B3 and NF-B4) with Bardet-Biedl syndrome-6 (BBS6; 605231) were homozygous for deletion of 280T of the MKKS gene, which resulted in a frameshift after amino acid phenylalanine-94, terminating the protein at amino acid 103. They found the same alteration in compound heterozygous state in 2 other patients (see 604896.0008 and 604896.0009), and it segregated with a haplotype-inferred prediction of a common ancestral chromosome in the 4 pedigrees. </p><p>Slavotinek et al. (2000) had independently studied the same Newfoundland families (their families 3 and 4) and identified a homozygous 1167delT mutation in each. In an erratum, the authors stated that their numbering differed from that of Katsanis et al. (2000) because they chose the 5-prime end of the sequence (GenBank AF221993) as '1,' whereas Katsanis et al. (2000) chose the A of the putative ATG. Moreover, they stated that according to nomenclature convention, the numbering should have been 1168delT and 281delT, respectively. </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 6</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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MKKS, LEU277PRO
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<br />
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SNP: rs74315398,
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gnomAD: rs74315398,
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ClinVar: RCV000005639, RCV000481638, RCV001267056, RCV001851675, RCV003230348, RCV003987313, RCV004532293, RCV005025009
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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 Newfoundland patient with Bardet-Biedl syndrome-6 (BBS6; 605231), Katsanis et al. (2000) found compound heterozygosity for 2 mutations in the MKKS gene: 280delT (604896.0007) and a missense mutation, leu277 to pro (L277P). The same patient was reported by Moore et al. (2005) as having been clinically diagnosed with Laurence-Moon syndrome (245800). Moore et al. (2005) considered their identification of mutations in the MKKS gene in a patient with Laurence-Moon syndrome as supporting the notion that Bardet-Biedl syndrome and Laurence-Moon syndrome are the same disorder. </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 6</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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MKKS, 2-BP DEL, 429CT AND 2-BP DEL, 433AG
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<br />
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SNP: rs2122235362,
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ClinVar: RCV002244221, RCV002502052, RCV003221313
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 affected members of a Newfoundland family segregating Bardet-Biedl syndrome-6 (BBS6; 605231), Katsanis et al. (2000) detected homozygosity for a complex 429delCT/433delAG allele of the MKKS gene that resulted in a frameshift of the termination of the protein at amino acid 157. Cloning and sequencing of the PCR product from 1 subject indicated that both deletions were on the same strand, suggesting that this mutation arose through a complex mechanism. </p><p>In an independent study of the same Newfoundland family (their family 2) segregating BBS6, Slavotinek et al. (2000) identified homozygosity for 2 deletions in the MKKS gene, which they designated 1316delC and 1324-1326delGTA, in exon 3 of the MKKS gene, predicting a frameshift. In an erratum, Slavotinek et al. (2000) attributed the discrepancy in the naming of this mutation to ambiguity in the nomenclature system and the absence of biologic data that could resolve the discrepancy. The parents in this family were related. The proband and her affected brother had retinitis pigmentosa, postaxial polydactyly, mild mental retardation, morbid obesity, lobulated kidneys with prominent calyces, and diabetes mellitus (diagnosed at ages 33 and 30, respectively). A deceased sister had similar phenotypic features (retinitis pigmentosa with blindness by age 13, BMI greater than 45, abnormal glucose tolerance test, an IQ of 64, vaginal atresia, and syndactyly of both feet). Both parents and the maternal grandfather were heterozygous for the deletions. </p><p>Katsanis et al. (2000) identified 2 affected members of another Newfoundland family with BBS6 who were compound heterozygous for this complex mutation and another frameshift mutation (604896.0007). </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>.0010 BARDET-BIEDL SYNDROME 6</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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MKKS, THR57ALA
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<br />
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SNP: rs74315399,
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gnomAD: rs74315399,
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ClinVar: RCV000005641, RCV000990288, RCV001376920, RCV002307354
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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 pedigree with Bardet-Biedl syndrome-6 (BBS6; 605231), Katsanis et al. (2000) found that 1 MKKS allele carried a thr57-to-ala (T57A) mutation. </p><p>Rachel et al. (2012) showed that MKKS with the T57A mutation exhibited reduced interaction with the C-terminal domain of the centrosomal protein CEP290 (610142). </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-text-font">
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<strong>.0011 MOVED TO 604896.0009</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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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0012 BARDET-BIEDL SYNDROME 2/6, DIGENIC</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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MKKS, GLN147TER
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<br />
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SNP: rs137853154,
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ClinVar: RCV000005643
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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 patient carrying 2 different termination codons in the BBS2 gene (606151.0003, 606151.0004), Katsanis et al. (2001) identified a nonsense mutation in the BBS6 gene, a glutamine-to-termination substitution at codon 147. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0013 BARDET-BIEDL SYNDROME 2/6, DIGENIC</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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MKKS, CYS499SER
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<br />
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SNP: rs281797259,
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ClinVar: RCV000005644
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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 patient who was compound heterozygous for 2 nonsense mutations in the BBS2 gene, a leu168 frameshift, leading to a termination codon at residue 170 (606151.0014), and an arg216-to-ter mutation (606151.0016), Katsanis et al. (2001) identified a third mutation in the MKKS gene, a cysteine-to-serine substitution at codon 499. </p><p>Rachel et al. (2012) showed that MKKS with the C499S mutation exhibited reduced interaction with the C-terminal domain of the centrosomal protein CEP290 (610142). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0014 BARDET-BIEDL SYNDROME 1, MODIFIER OF</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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MKKS, THR325PRO
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<br />
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SNP: rs137853156,
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ClinVar: RCV000005645
|
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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 1 of 2 sisters with BBS1 (209900), Badano et al. (2003) identified a 973A-C transversion in exon 3 of the MKKS gene, resulting in a thr325-to-pro (T325P) substitution which altered the 3-dimensional protein structure. Both sisters were compound heterozygous for mutations in the BBS1 gene: met390-to-arg (M390R; 209901.0001) and a 1-bp deletion (1650delC; 209901.0008). The sister with the T325P mutation was more severely affected than the sister without the mutation. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
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<div>
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<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Andersen, K. L., Echwald, S. M., Larsen, L. H., Hamid, Y. H., Glumer, C., Jorgensen, T., Borch-Johnsen, K., Andersen, T., Sorensen, T. I. A., Hansen, T., Pedersen, O.
|
|
<strong>Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity.</strong>
|
|
J. Clin. Endocr. Metab. 90: 225-230, 2005.
|
|
|
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|
|
[PubMed: 15483080]
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|
[Full Text: https://doi.org/10.1210/jc.2004-0465]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Badano, J. L., Kim, J. C., Hoskins, B. E., Lewis, R. A., Ansley, S. J., Cutler, D. J., Castellan, C., Beales, P. L., Leroux, M. R., Katsanis, N.
|
|
<strong>Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus.</strong>
|
|
Hum. Molec. Genet. 12: 1651-1659, 2003.
|
|
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|
|
[PubMed: 12837689]
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[Full Text: https://doi.org/10.1093/hmg/ddg188]
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</p>
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</li>
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<li>
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|
<p class="mim-text-font">
|
|
Beales, P. L., Katsanis, N., Lewis, R. A., Ansley, S. J., Elcioglu, N., Raza, J., Woods, M. O., Green, J. S., Parfrey, P. S., Davidson, W. S., Lupski, J. R.
|
|
<strong>Genetic and mutational analyses of a large multiethnic Bardet-Biedl cohort reveal a minor involvement of BBS6 and delineate the critical intervals of other loci.</strong>
|
|
Am. J. Hum. Genet. 68: 606-616, 2001. Note: Erratum: Am. J. Hum. Genet. 69: 922 only, 2001.
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|
|
[PubMed: 11179009]
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[Full Text: https://doi.org/10.1086/318794]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Billingsley, G., Bin, J., Fieggen, K. J., Duncan, J. L., Gerth, C., Ogata, K., Wodak, S. S., Traboulsi, E. I., Fishman, G. A., Paterson, A., Chitayat, D., Knueppel, T., Millan, J. M., Mitchell, G. A., Deveault, C., Heon, E.
|
|
<strong>Mutations in chaperonin-like BBS genes are a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population.</strong>
|
|
J. Med. Genet. 47: 453-463, 2010.
|
|
|
|
|
|
[PubMed: 20472660]
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[Full Text: https://doi.org/10.1136/jmg.2009.073205]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Fath, M. A., Mullins, R. F., Searby, C., Nishimura, D. Y., Wei, J., Rahmouni, K., Davis, R. E., Tayeh, M. K., Andrews, M., Yang, B., Sigmund, C. D., Stone, E. M., Sheffield, V. C.
|
|
<strong>Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome.</strong>
|
|
Hum. Molec. Genet. 14: 1109-1118, 2005.
|
|
|
|
|
|
[PubMed: 15772095]
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddi123]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hirayama, S., Yamazaki, Y., Kitamura, A., Oda, Y., Morito, D., Okawa, K., Kimura, H., Cyr, D. M., Kubota, H., Nagata, K.
|
|
<strong>MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination.</strong>
|
|
Molec. Biol. Cell 19: 899-911, 2008.
|
|
|
|
|
|
[PubMed: 18094050]
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|
|
[Full Text: https://doi.org/10.1091/mbc.e07-07-0631]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Karmous-Benailly, H., Martinovic, J., Gubler, M.-C., Sirot, Y., Clech, L., Ozilou, C., Auge, J., Brahimi, N., Etchevers, H., Detrait, E., Esculpavit, C., Audollent, S., and 17 others.
|
|
<strong>Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel syndrome.</strong>
|
|
Am. J. Hum. Genet. 76: 493-504, 2005.
|
|
|
|
|
|
[PubMed: 15666242]
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|
|
[Full Text: https://doi.org/10.1086/428679]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Katsanis, N., Ansley, S. J., Badano, J. L., Eichers, E. R., Lewis, R. A., Hoskins, B. E., Scambler, P. J., Davidson, W. S., Beales, P. L., Lupski, J. R.
|
|
<strong>Triallelic inheritance in Bardet-Biedl syndrome, a mendelian recessive disorder.</strong>
|
|
Science 293: 2256-2259, 2001.
|
|
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|
|
|
[PubMed: 11567139]
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[Full Text: https://doi.org/10.1126/science.1063525]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Katsanis, N., Beales, P. L., Woods, M. O., Lewis, R. A., Green, J. S., Parfrey, P. S., Ansley, S. J., Davidson, W. S., Lupski, J. R.
|
|
<strong>Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome.</strong>
|
|
Nature Genet. 26: 67-70, 2000.
|
|
|
|
|
|
[PubMed: 10973251]
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|
[Full Text: https://doi.org/10.1038/79201]
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</p>
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</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Moore, S. J., Green, J. S., Fan, Y., Bhogal, A. K., Dicks, E., Fernandez, B. A., Stefanelli, M., Murphy, C., Cramer, B. C., Dean, J. C. S., Beales, P. L., Katsanis, N., Bassett, A. S., Davidson, W. S., Parfrey, P. S.
|
|
<strong>Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study.</strong>
|
|
Am. J. Med. Genet. 132A: 352-360, 2005.
|
|
|
|
|
|
[PubMed: 15637713]
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|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30406]
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakane, T., Biesecker, L. G.
|
|
<strong>No evidence for triallelic inheritance of MKKS/BBS loci in Amish McKusick-Kaufman syndrome.</strong>
|
|
Am. J. Med. Genet. 138A: 32-34, 2005.
|
|
|
|
|
|
[PubMed: 16104012]
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|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30593]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Rachel, R. A., May-Simera, H. L., Veleri, S., Gotoh, N., Choi, B. Y., Murga-Zamalloa, C., McIntyre, J. C., Marek, J., Lopez, I., Hackett, A. N., Zhang, J., Brooks, M., and 12 others.
|
|
<strong>Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.</strong>
|
|
J. Clin. Invest. 122: 1233-1245, 2012. Note: Erratum: J. Clin. Invest. 122: 3025 only, 2012.
|
|
|
|
|
|
[PubMed: 22446187]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI60981]
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</p>
|
|
</li>
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|
<li>
|
|
<p class="mim-text-font">
|
|
Rahmouni, K., Fath, M. A., Seo, S., Thedens, D. R., Berry, C. J., Weiss, R., Nishimura, D. Y., Sheffield, V. C.
|
|
<strong>Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome.</strong>
|
|
J. Clin. Invest. 118: 1458-1467, 2008.
|
|
|
|
|
|
[PubMed: 18317593]
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|
|
[Full Text: https://doi.org/10.1172/JCI32357]
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|
</p>
|
|
</li>
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|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, C. A., Marsden, A. N., Rebagliati, M. R., Zhang, Q., Chamling, X., Searby, C. C., Baye, L. M., Sheffield, V. C., Slusarski, D. C.
|
|
<strong>Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein.</strong>
|
|
PLoS Genet. 13: e1006936, 2017. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 28753627]
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|
|
[Full Text: https://doi.org/10.1371/journal.pgen.1006936]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Shah, A. S., Farmen, S. L., Moninger, T. O., Businga, T. R., Andrews, M. P., Bugge, K., Searby, C. C., Nishimura, D., Brogden, K. A., Kline, J. N., Sheffield, V. C., Welsh, M. J.
|
|
<strong>Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 3380-3385, 2008.
|
|
|
|
|
|
[PubMed: 18299575]
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|
|
[Full Text: https://doi.org/10.1073/pnas.0712327105]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Slavotinek, A. M., Searby, C., Al-Gazali, L., Hennekam, R. C. M., Schrander-Stumpel, C., Orcana-Losa, M., Pardo-Reoyo, S., Cantani, A., Kumar, D., Capellini, Q., Neri, G., Zackai, E., Biesecker, L. G.
|
|
<strong>Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients.</strong>
|
|
Hum. Genet. 110: 561-567, 2002.
|
|
|
|
|
|
[PubMed: 12107442]
|
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|
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|
|
[Full Text: https://doi.org/10.1007/s00439-002-0733-3]
|
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|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Slavotinek, A. M., Stone, E. M., Mykytyn, K., Heckenlively, J. R., Green, J. S., Heon, E., Musarella, M. A., Parfrey, P. S., Sheffield, V. C., Biesecker, L. G.
|
|
<strong>Mutations in MKKS cause Bardet-Biedl syndrome.</strong>
|
|
Nature Genet. 26: 15-16, 2000. Note: Erratum: Nature Genet. 28: 193 only, 2001.
|
|
|
|
|
|
[PubMed: 10973238]
|
|
|
|
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[Full Text: https://doi.org/10.1038/79116]
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Stoetzel, C., Muller, J., Laurier, V., Davis, E. E., Zaghloul, N. A., Vicaire, S., Jacquelin, C., Plewniak, F., Leitch, C. C., Sarda, P., Hamel, C., de Ravel, T. J. L., and 10 others.
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<strong>Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome.</strong>
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Am. J. Hum. Genet. 80: 1-11, 2007.
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[PubMed: 17160889]
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[Full Text: https://doi.org/10.1086/510256]
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Stone, D. L., Slavotinek, A., Bouffard, G. G., Banerjee-Basu, S., Baxevanis, A. D., Barr, M., Biesecker, L. G.
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<strong>Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome.</strong>
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Nature Genet. 25: 79-82, 2000.
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[PubMed: 10802661]
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[Full Text: https://doi.org/10.1038/75637]
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Patricia A. Hartz - updated : 02/12/2018<br>Paul J. Converse - updated : 12/13/2017<br>Marla J. F. O'Neill - updated : 12/29/2009<br>Marla J. F. O'Neill - updated : 7/22/2008<br>Patricia A. Hartz - updated : 7/22/2008<br>Patricia A. Hartz - updated : 5/21/2008<br>George E. Tiller - updated : 5/19/2008<br>John A. Phillips, III - updated : 4/10/2006<br>Cassandra L. Kniffin - updated : 9/22/2005<br>George E. Tiller - updated : 5/24/2005<br>Victor A. McKusick - updated : 2/9/2005<br>Victor A. McKusick - updated : 8/13/2002<br>Ada Hamosh - updated : 10/3/2001<br>Victor A. McKusick - updated : 8/24/2000
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Ada Hamosh : 4/29/2000
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