3431 lines
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Entry
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- *608132 - TETRATRICOPEPTIDE REPEAT DOMAIN-CONTAINING PROTEIN 8; TTC8
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- OMIM
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<p>
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<span class="h4">*608132</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</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/608132">Table View</a>
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<a href="#references"><strong>References</strong></a>
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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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<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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<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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<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=ENSG00000165533;t=ENST00000380656" 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=123016" 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=608132" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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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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<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=ENSG00000165533;t=ENST00000380656" 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_001288781,NM_001288782,NM_001288783,NM_001366535,NM_001366536,NM_144596,NM_198309,NM_198310,NR_159362,XM_011536433,XM_011536434" 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_144596" 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=608132" 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="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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<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=10484&isoform_id=10484_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/TTC8" 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/16306755,20070977,28071094,28193114,28193236,28207845,37723876,37723878,38146008,38146012,38373432,52545844,53759120,66267598,119601801,119601802,119601803,119601804,119601805,119601806,119601807,119601808,193784914,193787574,194382156,308153511,571026683,571026685,571026687,767979724,767979726,957951770,957951772,957951775,957951778,957951781,957951784,1488192443,1488192447,2462538882,2462538884" 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/Q8TAM2" 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=123016" 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=ENSG00000165533;t=ENST00000380656" 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=TTC8" 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=TTC8" 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+123016" 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/TTC8" 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:123016" 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/123016" 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=chr14&hgg_gene=ENST00000380656.7&hgg_start=88824153&hgg_end=88881079&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:20087" 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:20087" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608132[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=608132[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/TTC8/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000165533" 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=TTC8" 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=TTC8" 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=TTC8" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=TTC8&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/PA134877629" 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:20087" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0031255.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1923510" 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/TTC8#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:1923510" 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/123016/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA001984/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=123016" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00000244;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-8846" 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=TTC8&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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608132
|
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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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TETRATRICOPEPTIDE REPEAT DOMAIN-CONTAINING PROTEIN 8; TTC8
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
BBS8 GENE
|
|
</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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TTC8" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TTC8</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/14/441?start=-3&limit=10&highlight=441">14q31.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:88824153-88881079&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'})">14:88,824,153-88,881,079</a> </span>
|
|
</em>
|
|
</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>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=613464,615985" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/14/441?start=-3&limit=10&highlight=441">
|
|
14q31.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Retinitis pigmentosa 51
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613464"> 613464 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
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</td>
|
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|
|
|
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|
|
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</tr>
|
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|
|
|
|
|
|
|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Bardet-Biedl syndrome 8
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/615985"> 615985 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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<p>TTC8 is 1 of 7 BBS proteins that form the stable core of a protein complex required for ciliogenesis (<a href="#7" class="mim-tip-reference" title="Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peranen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C., Jackson, P. K. <strong>A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.</strong> Cell 129: 1201-1213, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17574030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17574030</a>] [<a href="https://doi.org/10.1016/j.cell.2007.03.053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17574030">Nachury et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17574030" 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="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> fragmented the BBS4 gene (<a href="/entry/600374">600374</a>) into 8 overlapping segments and searched the conceptual translation of the draft human genome and the EST database. In 1 instance they observed an alignment between 3 consecutive TPRs of BBS4 and a contiguous region of the hypothetical protein TTC8. The authors identified 2 alternatively spliced isoforms. RT-PCR analysis of human tissues detected strong expression in testis, ovary, lung, brain, liver, pancreas, and fetal kidney, with lower expression in heart, kidney, placenta, thymus, and spleen. The predicted protein contains 8 C-terminal TPRs and exhibits significant similarity to a prokaryotic domain pilF, involved in twitching mobility and type IV pilus assembly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520415" 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="Riazuddin, S. A., Iqbal, M., Wang, Y., Masuda, T., Chen, Y., Bowne, S., Sullivan, L. S., Waseem, N. H., Bhattacharya, S., Daiger, S. P., Zhang, K., Khan, S. N., Riazuddin, S., Hejtmancik, J. F., Sieving, P. A., Zack, D. J., Katsanis, N. <strong>A splice-site mutation in a retina-specific exon of BBS8 causes nonsyndromic retinitis pigmentosa.</strong> Am. J. Hum. Genet. 86: 805-812, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20451172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20451172</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20451172[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2010.04.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20451172">Riazuddin et al. (2010)</a> noted that full-length TTC8 contains 515 amino acids and includes exon 2A, whereas a shorter TTC8 isoform lacking exon 2A contains 505 amino acids. A third isoform lacking exon 2A and exon 5 contains 475 amino acids. RT-PCR analysis of mouse tissues that express Ttc8 detected the Ttc8 isoform containing exon 2A exclusively in retina, and further analysis of mouse retinal tissues obtained by laser-capture microdissection found the exon-2A isoform mostly in the photoreceptor layer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20451172" 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 RT-PCR and mouse knockout models, <a href="#6" class="mim-tip-reference" title="Murphy, D., Singh, R., Kolandaivelu, S., Ramamurthy, V., Stoilov, P. <strong>Alternative splicing shapes the phenotype of a mutation in BBS8 to cause nonsyndromic retinitis pigmentosa.</strong> Molec. Cell. Biol. 35: 1860-1870, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25776555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25776555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25776555[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/10.1128/MCB.00040-15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25776555">Murphy et al. (2015)</a> found that full-length Ttc8, including exon 2A, was expressed almost exclusively in retinal photoreceptors. All other mouse tissues expressed Ttc8 transcripts lacking exon 2A. Inclusion of exon 2A in Ttc8 was not detected in developing mouse until postnatal day 0, after which exon 2A inclusion increased rapidly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25776555" 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="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> determined that the TTC8 gene contains 14 exons. Subsequently, <a href="#8" class="mim-tip-reference" title="Riazuddin, S. A., Iqbal, M., Wang, Y., Masuda, T., Chen, Y., Bowne, S., Sullivan, L. S., Waseem, N. H., Bhattacharya, S., Daiger, S. P., Zhang, K., Khan, S. N., Riazuddin, S., Hejtmancik, J. F., Sieving, P. A., Zack, D. J., Katsanis, N. <strong>A splice-site mutation in a retina-specific exon of BBS8 causes nonsyndromic retinitis pigmentosa.</strong> Am. J. Hum. Genet. 86: 805-812, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20451172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20451172</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20451172[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2010.04.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20451172">Riazuddin et al. (2010)</a> identified the retina-specific exon 2A. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20451172+14520415" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Murphy, D., Singh, R., Kolandaivelu, S., Ramamurthy, V., Stoilov, P. <strong>Alternative splicing shapes the phenotype of a mutation in BBS8 to cause nonsyndromic retinitis pigmentosa.</strong> Molec. Cell. Biol. 35: 1860-1870, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25776555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25776555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25776555[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/10.1128/MCB.00040-15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25776555">Murphy et al. (2015)</a> identified intronic sequences 5-prime and 3-prime of TTC8 exon 2A that contained retina-specific splicing enhancers for inclusion of exon 2A in photoreceptor cells only. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25776555" 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="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> stated that the TTC8 gene maps to chromosome 14q32.11. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520415" 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="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> found that TTC8 colocalizes with gamma-tubulin (see <a href="/entry/191135">191135</a>), BBS4, and PCM1 (<a href="/entry/600299">600299</a>) in the centrosome. PCM1 is thought to be involved in centriolar replication during ciliogenesis (<a href="#4" class="mim-tip-reference" title="Kubo, A., Sasaki, H., Yuba-Kubo, A., Tsukita, S., Shiina, N. <strong>Centriolar satellites: molecular characterization, ATP-dependent movement toward centrioles and possible involvement in ciliogenesis.</strong> J. Cell Biol. 147: 969-979, 1999. Note: Erratum: J. Cell Biol. 147: 1585 only, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10579718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10579718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10579718[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1083/jcb.147.5.969" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10579718">Kubo et al., 1999</a>). Immunoprecipitation indicated that TTC8 binds to the C terminus of PCM1. A polyclonal antibody against TTC8 stained ciliated structures in 12-day-old mice, including maturing spermatids, the connecting cilium of the retina, and bronchial epithelial cells. In mouse embryos at 14 and 16 days, <a href="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> detected specific localization in the telencephalon, with prominent staining at the developing ependymal cell layer and olfactory epithelium. <a href="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> found that all C. elegans BBS homologs studied are expressed exclusively in ciliated neurons and contain regulatory elements for RFX, a transcription factor that modulates expression of genes associated with ciliogenesis and intraflagellar transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14520415+10579718" 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="Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peranen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C., Jackson, P. K. <strong>A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.</strong> Cell 129: 1201-1213, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17574030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17574030</a>] [<a href="https://doi.org/10.1016/j.cell.2007.03.053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17574030">Nachury et al. (2007)</a> found that BBS1 (<a href="/entry/209901">209901</a>), BBS2 (<a href="/entry/606151">606151</a>), BBS4, BBS5 (<a href="/entry/603650">603650</a>), BBS7 (<a href="/entry/607590">607590</a>), BBS8, and BBS9 (<a href="/entry/607968">607968</a>) copurified in stoichiometric amounts from human retinal pigment epithelium (RPE) cells and from mouse testis. PCM1 and alpha-tubulin (see <a href="/entry/602529">602529</a>)/beta-tubulin (<a href="/entry/191130">191130</a>) copurified in substoichiometric amounts. The apparent molecular mass of the complex, which <a href="#7" class="mim-tip-reference" title="Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peranen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C., Jackson, P. K. <strong>A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.</strong> Cell 129: 1201-1213, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17574030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17574030</a>] [<a href="https://doi.org/10.1016/j.cell.2007.03.053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17574030">Nachury et al. (2007)</a> called the BBSome, was 438 kD, and it had a sedimentation coefficient of 14S. The complex localized with PCM1 to nonmembranous centriolar satellites in the cytoplasm and, in the absence of PCM1, to the ciliary membrane. Cotransfection and immunoprecipitation experiments suggested that BBS9 was the complex-organizing subunit and that BBS5 mediated binding to phospholipids, predominantly phosphatidylinositol 3-phosphate. BBS1 mediated interaction with RABIN8 (RAB3IP; <a href="/entry/608686">608686</a>), the guanine nucleotide exchange factor for the small G protein RAB8 (RAB8A; <a href="/entry/165040">165040</a>). <a href="#7" class="mim-tip-reference" title="Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peranen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C., Jackson, P. K. <strong>A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.</strong> Cell 129: 1201-1213, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17574030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17574030</a>] [<a href="https://doi.org/10.1016/j.cell.2007.03.053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17574030">Nachury et al. (2007)</a> found that RAB8 promoted ciliary membrane growth through fusion of exocytic vesicles to the base of the ciliary membrane. They concluded that BBS proteins likely function in membrane trafficking to the primary cilium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17574030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Loktev, A. V., Zhang, Q., Beck, J. S., Searby, C. C., Scheetz, T. E., Bazan, J. F., Slusarski, D. C., Sheffield, V. C., Jackson, P. K., Nachury, M. V. <strong>A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.</strong> Dev. Cell 15: 854-865, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19081074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19081074</a>] [<a href="https://doi.org/10.1016/j.devcel.2008.11.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19081074">Loktev et al. (2008)</a> found that BBIP10 (<a href="/entry/613605">613605</a>) copurified and cosedimented with the BBS protein complex from RPE cells. Knockdown of BBIP10 in RPE cells via small interfering RNA compromised assembly of the BBS protein complex and caused failure of ciliogenesis. Knockdown of BBS1, BBS5, or PCM1 resulted in a similar failure of ciliogenesis in RPE cells. Depletion of BBIP10 or BBS8 increased the frequency of centrosome splitting in interphase cells. BBIP10 also had roles in cytoplasmic microtubule stabilization and acetylation that appeared to be independent of its role in assembly of the BBS protein complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19081074" 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 a protein pull-down assay with homogenized bovine retina, <a href="#3" class="mim-tip-reference" title="Jin, H., White, S. R., Shida, T., Schulz, S., Aguiar, M., Gygi, S. P., Bazan, J. F., Nachury, M. V. <strong>The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia.</strong> Cell 141: 1208-1219, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20603001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20603001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20603001[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2010.05.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20603001">Jin et al. (2010)</a> showed that ARL6 (<a href="/entry/608845">608845</a>) bound the BBS protein complex. Depletion of ARL6 in human RPE cells did not affect assembly of the complex, but it blocked its localization to cilia. Targeting of ARL6 and the protein complex to cilia required GTP binding by ARL6, but not ARL6 GTPase activity. When in the GTP-bound form, the N-terminal amphipathic helix of ARL6 bound brain lipid liposomes and recruited the BBS protein complex. Upon recruitment, the complex appeared to polymerize into an electron-dense planar coat, and it functioned in lateral transport of test cargo proteins to ciliary membranes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20603001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By mass spectrometric analysis of transgenic mouse testis, <a href="#9" class="mim-tip-reference" title="Seo, S., Zhang, Q., Bugge, K., Breslow, D. K., Searby, C. C., Nachury, M. V., Sheffield, V. C. <strong>A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.</strong> PLoS Genet. 7: e1002358, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22072986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22072986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22072986[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.1002358" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22072986">Seo et al. (2011)</a> found that Lxtfl1 (<a href="/entry/606568">606568</a>) copurified with human BBS4 and with the core mouse BBS complex subunits Bbs1, Bbs2, Bbs5, Bbs7, Bbs8, and Bbs9. Immunohistochemical analysis of human RPE cells showed colocalization of LXTFL1 and BBS9 in cytoplasmic punctae. Use of small interfering RNA revealed distinct functions for each BBS subunit in BBS complex assembly and trafficking. LZTFL1 depletion and overexpression studies showed a negative role for LZTFL1 in BBS complex trafficking, but no effect of LZTFL1 on BBS complex assembly. Mutation analysis revealed that the C-terminal half of Lztfl1 interacted with the C-terminal domain of Bbs9 and that the N-terminal half of Lztfl1 negatively regulated BBS complex trafficking. Depletion of several BBS subunits and LZTFL1 also altered Hedgehog (SHH; <a href="/entry/600725">600725</a>) signaling, as measured by GLI1 (<a href="/entry/165220">165220</a>) expression and ciliary trafficking of SMO (SMOH; <a href="/entry/601500">601500</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22072986" 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 computational analysis, <a href="#3" class="mim-tip-reference" title="Jin, H., White, S. R., Shida, T., Schulz, S., Aguiar, M., Gygi, S. P., Bazan, J. F., Nachury, M. V. <strong>The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia.</strong> Cell 141: 1208-1219, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20603001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20603001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20603001[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2010.05.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20603001">Jin et al. (2010)</a> found that the BBS protein complex shares structural features with the canonical coat complexes COPI (<a href="/entry/601924">601924</a>), COPII (see <a href="/entry/610511">610511</a>), and clathrin AP1 (see <a href="/entry/603531">603531</a>). BBS4 and BBS8 consist almost entirely of tetratricopeptide repeats (TPRs) (13 and 12.5 TPRs, respectively), which are predicted to fold into extended rod-shaped alpha solenoids. BBS1, BBS2, BBS7, and BBS9 each have an N-terminal beta-propeller fold followed by an amphipathic helical linker and a gamma-adaptin (AP1G1; <a href="/entry/603533">603533</a>) ear motif. In BBS2, BBS7, and BBS9, the ear motif is followed by an alpha/beta platform domain and an alpha helix. In BBS1, a 4-helix bundle is inserted between the second and third blades of the beta propeller. BBS5 contains 2 pleckstrin (PLEK; <a href="/entry/173570">173570</a>) homology domains and a 3-helix bundle, while BBIP10 consists of 2 alpha helices. <a href="#3" class="mim-tip-reference" title="Jin, H., White, S. R., Shida, T., Schulz, S., Aguiar, M., Gygi, S. P., Bazan, J. F., Nachury, M. V. <strong>The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia.</strong> Cell 141: 1208-1219, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20603001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20603001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20603001[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2010.05.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20603001">Jin et al. (2010)</a> concluded that the abundance of beta propellers, alpha solenoids, and appendage domains inside the BBS protein complex suggests that it shares an evolutionary relationship with canonical coat complexes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20603001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Bardet-Biedl Syndrome 8</em></strong></p><p>
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<a href="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> screened the TTC8 gene in a cohort of 120 unrelated patients with Bardet-Biedl syndrome (see BBS8, <a href="/entry/615985">615985</a>) and identified homozygous alterations in patients from 3 families. All 8 affected individuals in these 3 families had a homozygous mutant genotype and exhibited classic BBS signs. These mutations were not identified in 192 ethnically matched control chromosomes. One of the affected family members with BBS due to TTC8 mutations demonstrated situs inversus. The association between BBS and the situs inversus phenotype was not coincidental, although the presence of situs in only 1 of 3 affected family members suggested that the defect was one of randomization of left-right symmetry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520415" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> demonstrated that BBS is probably caused by a defect of the basal body of ciliated cells. The TTC8 gene, mutations in which are responsible for BBS8, encodes a protein with a prokaryotic domain, pilF, involved in pilus formation and twitching mobility. In 1 family a homozygous null BBS8 mutation (<a href="#0002">608132.0002</a>) led to BBS with randomization of left-right body axis symmetry, a defect of the nodal cilium. <a href="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> showed that TTC8 localizes to centrosomes and basal bodies and colocalizes with gamma-tubulin (see <a href="/entry/191135">191135</a>), BBS4 (<a href="/entry/600374">600374</a>), and PCM1 (<a href="/entry/600299">600299</a>). Furthermore, <a href="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> found that all available C. elegans BBS homologs are expressed exclusively in ciliated neurons and contain regulatory elements for RFX, a transcription factor that modulates the expression of genes associated with ciliogenesis and intraflagellar transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520415" 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="#10" class="mim-tip-reference" title="Stoetzel, C., Laurier, V., Faivre, L., Megarbane, A., Perrin-Schmitt, F., Verloes, A., Bonneau, D., Mandel, J.-L., Cossee, M., Dollfus, H. <strong>BBS8 is rarely mutated in a cohort of 128 Bardet-Biedl syndrome families.</strong> J. Hum. Genet. 51: 81-84, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16308660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16308660</a>] [<a href="https://doi.org/10.1007/s10038-005-0320-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16308660">Stoetzel et al. (2006)</a> identified homozygous mutations in the TTC8 gene (<a href="#0003">608132.0003</a> and <a href="#0004">608132.0004</a>) in 2 of 128 BBS families. One additional family had a heterozygous mutation. <a href="#10" class="mim-tip-reference" title="Stoetzel, C., Laurier, V., Faivre, L., Megarbane, A., Perrin-Schmitt, F., Verloes, A., Bonneau, D., Mandel, J.-L., Cossee, M., Dollfus, H. <strong>BBS8 is rarely mutated in a cohort of 128 Bardet-Biedl syndrome families.</strong> J. Hum. Genet. 51: 81-84, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16308660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16308660</a>] [<a href="https://doi.org/10.1007/s10038-005-0320-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16308660">Stoetzel et al. (2006)</a> concluded that TTC8 mutations account for only about 2% of BBS families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16308660" 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>Retinitis Pigmentosa 51</em></strong></p><p>
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In a large consanguineous Pakistani family segregating autosomal recessive retinitis pigmentosa (RP51; <a href="/entry/613464">613464</a>) mapping to chromosome 14q, <a href="#8" class="mim-tip-reference" title="Riazuddin, S. A., Iqbal, M., Wang, Y., Masuda, T., Chen, Y., Bowne, S., Sullivan, L. S., Waseem, N. H., Bhattacharya, S., Daiger, S. P., Zhang, K., Khan, S. N., Riazuddin, S., Hejtmancik, J. F., Sieving, P. A., Zack, D. J., Katsanis, N. <strong>A splice-site mutation in a retina-specific exon of BBS8 causes nonsyndromic retinitis pigmentosa.</strong> Am. J. Hum. Genet. 86: 805-812, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20451172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20451172</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20451172[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2010.04.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20451172">Riazuddin et al. (2010)</a> sequenced candidate genes and identified a homozygous splice site mutation in the TTC8 gene (<a href="#0005">608132.0005</a>) that segregated with disease and was not found in controls. None of the affected individuals had evidence of syndromic disease or any features consistent with BBS. The mutation mapped to the splice acceptor site of exon 2A of the TTC8 gene. RT-PCR analysis of mouse tissues that express Ttc8 detected Ttc8 isoforms containing exon 2A exclusively in retina, and further analysis of mouse retinal tissues obtained by laser-capture microdissection found the exon-2A isoform mostly in the photoreceptor layer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20451172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 affected individuals from a consanguineous North Indian family with nonsyndromic RP and macular degeneration, <a href="#2" class="mim-tip-reference" title="Goyal, S., Jager, M., Robinson, P. N., Vanita, V. <strong>Confirmation of TTC8 as a disease gene for nonsyndromic autosomal recessive retinitis pigmentosa (RP51).</strong> Clin. Genet. 89: 454-460, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26195043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26195043</a>] [<a href="https://doi.org/10.1111/cge.12644" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26195043">Goyal et al. (2016)</a> identified homozygosity for a missense mutation in the TTC8 gene (Q449H; <a href="#0006">608132.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26195043" 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>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>6 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=608132[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777806 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777806;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=rs587777806" 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=rs587777806" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 families of Saudi Arabian lineage with Bardet-Biedl syndrome (BBS8; <a href="/entry/615985">615985</a>), <a href="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> identified homozygosity for a 6-bp in-frame deletion in exon 6 of the TTC8 gene that eliminated 2 amino acids (187-188delEY). Both the E (glu) and Y (tyr) residues at the those locations are conserved in 16 TTC8 homologs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520415" 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> rs587777807 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777807;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/rs587777807?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=rs587777807" 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=rs587777807" 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 consanguineous Pakistani family with Bardet-Biedl syndrome (BBS8; <a href="/entry/615985">615985</a>), <a href="#1" class="mim-tip-reference" title="Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N. <strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong> Nature 425: 628-633, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>] [<a href="https://doi.org/10.1038/nature02030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520415">Ansley et al. (2003)</a> identified a homozygous 3-bp deletion that abolished the donor sequence at the splice junction of exon 10 (IVS10+2-4delTGC) in all 3 patients, but not their unaffected sister. The authors predicted this mutation to result in a read-through culminating in an intronic stop codon. RT-PCR detected no TTC8 expression in cultured renal tubular cells and skin fibroblasts from 2 affected sibs, but detected expression in cells from their unaffected sister, who was heterozygous for the mutation, and in a control cell line. One of the affected sibs manifested situs inversus, which was not thought to be coincidental but to represent a defect of randomization of left-right symmetry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520415" 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> rs119103286 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103286;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/rs119103286?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=rs119103286" 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=rs119103286" 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=RCV000002639 OR RCV000203928 OR RCV000415339 OR RCV001074706 OR RCV001197566 OR RCV003415630 OR RCV005007809" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002639, RCV000203928, RCV000415339, RCV001074706, RCV001197566, RCV003415630, RCV005007809" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002639...</a>
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<p>In 3 sibs with Bardet-Biedl syndrome (BBS8; <a href="/entry/615985">615985</a>), <a href="#10" class="mim-tip-reference" title="Stoetzel, C., Laurier, V., Faivre, L., Megarbane, A., Perrin-Schmitt, F., Verloes, A., Bonneau, D., Mandel, J.-L., Cossee, M., Dollfus, H. <strong>BBS8 is rarely mutated in a cohort of 128 Bardet-Biedl syndrome families.</strong> J. Hum. Genet. 51: 81-84, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16308660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16308660</a>] [<a href="https://doi.org/10.1007/s10038-005-0320-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16308660">Stoetzel et al. (2006)</a> identified a homozygous 459G-A transition affecting the last G of exon 4 of the TTC8 gene and predicted to abolish the splice site of exon 4. One affected sib also had a heterozygous mutation in the BBS7 gene (<a href="/entry/607590">607590</a>), but the authors concluded that it was not pathogenic, since no clinical differences were noted between the sib with the BBS7 mutation and the sibs without the BBS7 mutation. The children were born of consanguineous parents of North African descent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16308660" 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> rs587777808 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777808;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/rs587777808?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=rs587777808" 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=rs587777808" 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=RCV000002640 OR RCV001699099" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002640, RCV001699099" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002640...</a>
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<p>In a child with Bardet-Biedl syndrome (BBS8; <a href="/entry/615985">615985</a>), born of consanguineous Lebanese parents, <a href="#10" class="mim-tip-reference" title="Stoetzel, C., Laurier, V., Faivre, L., Megarbane, A., Perrin-Schmitt, F., Verloes, A., Bonneau, D., Mandel, J.-L., Cossee, M., Dollfus, H. <strong>BBS8 is rarely mutated in a cohort of 128 Bardet-Biedl syndrome families.</strong> J. Hum. Genet. 51: 81-84, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16308660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16308660</a>] [<a href="https://doi.org/10.1007/s10038-005-0320-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16308660">Stoetzel et al. (2006)</a> identified a homozygous G-to-A splice site mutation in intron 6 of the TTC8 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16308660" 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">rs587777809 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777809;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=rs587777809" 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=rs587777809" 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=RCV000002641 OR RCV004794322" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002641, RCV004794322" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002641...</a>
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<p>In 4 affected members of a large consanguineous Pakistani family segregating autosomal recessive retinitis pigmentosa (RP51; <a href="/entry/613464">613464</a>), <a href="#8" class="mim-tip-reference" title="Riazuddin, S. A., Iqbal, M., Wang, Y., Masuda, T., Chen, Y., Bowne, S., Sullivan, L. S., Waseem, N. H., Bhattacharya, S., Daiger, S. P., Zhang, K., Khan, S. N., Riazuddin, S., Hejtmancik, J. F., Sieving, P. A., Zack, D. J., Katsanis, N. <strong>A splice-site mutation in a retina-specific exon of BBS8 causes nonsyndromic retinitis pigmentosa.</strong> Am. J. Hum. Genet. 86: 805-812, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20451172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20451172</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20451172[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2010.04.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20451172">Riazuddin et al. (2010)</a> identified homozygosity for a -2A-G transition in intron 1 of the TTC8 gene, predicted to result in deletion of 10 amino acids from the protein. The mutation segregated with the disease and was not found in 384 Pakistani control chromosomes or 384 chromosomes of northern European descent. None of the affected individuals had evidence of syndromic disease or any features consistent with BBS. The mutation mapped to a highly conserved splice acceptor site of exon 2A of the TTC8 gene. RT-PCR analysis of mouse tissues that express Ttc8 detected Ttc8 isoforms containing exon 2A exclusively in retina, and further analysis of mouse retinal tissues obtained by laser-capture microdissection found the exon-2A isoform mostly in the photoreceptor layer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20451172" 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 subretinal injection and electroporation of a fluorescent splicing reporter in mice, <a href="#6" class="mim-tip-reference" title="Murphy, D., Singh, R., Kolandaivelu, S., Ramamurthy, V., Stoilov, P. <strong>Alternative splicing shapes the phenotype of a mutation in BBS8 to cause nonsyndromic retinitis pigmentosa.</strong> Molec. Cell. Biol. 35: 1860-1870, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25776555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25776555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25776555[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/10.1128/MCB.00040-15" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25776555">Murphy et al. (2015)</a> found that the -2A-G transition in intron 1 of the TTC8 gene disrupted the 5-prime splice site of exon 2A and forced the use of a cryptic splice site 7 nucleotides downstream of the mutation. Missplicing of exon 2A in retina resulted in premature termination and elimination of TTC8 protein in photoreceptors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25776555" 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 RETINITIS PIGMENTOSA 51</strong>
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TTC8, GLN449HIS
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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> rs876661403 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs876661403;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/rs876661403?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=rs876661403" 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=rs876661403" 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=RCV000223936" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000223936" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000223936</a>
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<p>In 3 affected individuals from a consanguineous North Indian family with nonsyndromic RP and macular degeneration (RP51; <a href="/entry/613464">613464</a>), <a href="#2" class="mim-tip-reference" title="Goyal, S., Jager, M., Robinson, P. N., Vanita, V. <strong>Confirmation of TTC8 as a disease gene for nonsyndromic autosomal recessive retinitis pigmentosa (RP51).</strong> Clin. Genet. 89: 454-460, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26195043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26195043</a>] [<a href="https://doi.org/10.1111/cge.12644" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26195043">Goyal et al. (2016)</a> identified homozygosity for a c.1347G-C transversion (c.1347G-C, NM_144596.3) in exon 13 of the TTC8 gene, resulting in a gln449-to-his (Q449H) substitution at a highly conserved residue. The mutation segregated with disease in the family and was not found in 100 ethnically matched controls. The authors noted that the mutation involved the last nucleotide of exon 13, thereby affecting the 5-prime splice site consensus sequence; however, RNA was not available to test the effects of the mutation on splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26195043" 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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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Ansley2003" class="mim-anchor"></a>
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Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N.
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<strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong>
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Nature 425: 628-633, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520415</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520415" 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/nature02030" target="_blank">Full Text</a>]
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Goyal, S., Jager, M., Robinson, P. N., Vanita, V.
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<strong>Confirmation of TTC8 as a disease gene for nonsyndromic autosomal recessive retinitis pigmentosa (RP51).</strong>
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Clin. Genet. 89: 454-460, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26195043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26195043</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26195043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/cge.12644" target="_blank">Full Text</a>]
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Jin, H., White, S. R., Shida, T., Schulz, S., Aguiar, M., Gygi, S. P., Bazan, J. F., Nachury, M. V.
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<strong>The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia.</strong>
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Cell 141: 1208-1219, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20603001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20603001</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20603001[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=20603001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.cell.2010.05.015" target="_blank">Full Text</a>]
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Kubo, A., Sasaki, H., Yuba-Kubo, A., Tsukita, S., Shiina, N.
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<strong>Centriolar satellites: molecular characterization, ATP-dependent movement toward centrioles and possible involvement in ciliogenesis.</strong>
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J. Cell Biol. 147: 969-979, 1999. Note: Erratum: J. Cell Biol. 147: 1585 only, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10579718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10579718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10579718[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=10579718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1083/jcb.147.5.969" target="_blank">Full Text</a>]
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Loktev, A. V., Zhang, Q., Beck, J. S., Searby, C. C., Scheetz, T. E., Bazan, J. F., Slusarski, D. C., Sheffield, V. C., Jackson, P. K., Nachury, M. V.
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<strong>A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.</strong>
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Dev. Cell 15: 854-865, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19081074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19081074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19081074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.devcel.2008.11.001" target="_blank">Full Text</a>]
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<a id="Murphy2015" class="mim-anchor"></a>
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Murphy, D., Singh, R., Kolandaivelu, S., Ramamurthy, V., Stoilov, P.
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<strong>Alternative splicing shapes the phenotype of a mutation in BBS8 to cause nonsyndromic retinitis pigmentosa.</strong>
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Molec. Cell. Biol. 35: 1860-1870, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25776555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25776555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25776555[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=25776555" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1128/MCB.00040-15" target="_blank">Full Text</a>]
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<a id="Nachury2007" class="mim-anchor"></a>
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Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peranen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C., Jackson, P. K.
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<strong>A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.</strong>
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Cell 129: 1201-1213, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17574030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17574030</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17574030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.cell.2007.03.053" target="_blank">Full Text</a>]
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<a id="Riazuddin2010" class="mim-anchor"></a>
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Riazuddin, S. A., Iqbal, M., Wang, Y., Masuda, T., Chen, Y., Bowne, S., Sullivan, L. S., Waseem, N. H., Bhattacharya, S., Daiger, S. P., Zhang, K., Khan, S. N., Riazuddin, S., Hejtmancik, J. F., Sieving, P. A., Zack, D. J., Katsanis, N.
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<strong>A splice-site mutation in a retina-specific exon of BBS8 causes nonsyndromic retinitis pigmentosa.</strong>
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Am. J. Hum. Genet. 86: 805-812, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20451172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20451172</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20451172[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=20451172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2010.04.001" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Seo2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Seo, S., Zhang, Q., Bugge, K., Breslow, D. K., Searby, C. C., Nachury, M. V., Sheffield, V. C.
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<strong>A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.</strong>
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PLoS Genet. 7: e1002358, 2011. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22072986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22072986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22072986[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=22072986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1371/journal.pgen.1002358" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Stoetzel2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Stoetzel, C., Laurier, V., Faivre, L., Megarbane, A., Perrin-Schmitt, F., Verloes, A., Bonneau, D., Mandel, J.-L., Cossee, M., Dollfus, H.
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<strong>BBS8 is rarely mutated in a cohort of 128 Bardet-Biedl syndrome families.</strong>
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J. Hum. Genet. 51: 81-84, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16308660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16308660</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16308660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10038-005-0320-2" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 6/2/2016
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 5/31/2016<br>Patricia A. Hartz - updated : 11/12/2012<br>Patricia A. Hartz - updated : 10/13/2010<br>Marla J. F. O'Neill - updated : 6/21/2010<br>Cassandra L. Kniffin - updated : 3/2/2006
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh : 9/29/2003
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</span>
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</div>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 06/02/2016
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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mgross : 6/2/2016<br>carol : 5/31/2016<br>carol : 2/5/2016<br>carol : 1/30/2016<br>alopez : 10/17/2014<br>alopez : 10/16/2014<br>mgross : 2/26/2013<br>mgross : 11/12/2012<br>mgross : 10/15/2010<br>terry : 10/13/2010<br>wwang : 6/25/2010<br>wwang : 6/24/2010<br>terry : 6/21/2010<br>wwang : 3/7/2006<br>ckniffin : 3/2/2006<br>carol : 8/19/2004<br>alopez : 10/16/2003<br>alopez : 10/9/2003<br>alopez : 9/29/2003
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</span>
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<div class="container visible-print-block">
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<span class="mim-font">
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<strong>*</strong> 608132
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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TETRATRICOPEPTIDE REPEAT DOMAIN-CONTAINING PROTEIN 8; TTC8
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</h3>
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</div>
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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BBS8 GENE
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<br />
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TTC8</em></strong>
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<strong>
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<em>
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Cytogenetic location: 14q31.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 14:88,824,153-88,881,079 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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<td rowspan="2">
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<span class="mim-font">
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14q31.3
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<td>
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<span class="mim-font">
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?Retinitis pigmentosa 51
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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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613464
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<span class="mim-font">
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Bardet-Biedl syndrome 8
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</span>
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</td>
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<span class="mim-font">
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615985
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<td>
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<span class="mim-font">
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Autosomal recessive
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</td>
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<td>
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<span class="mim-font">
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3
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</table>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>TTC8 is 1 of 7 BBS proteins that form the stable core of a protein complex required for ciliogenesis (Nachury et al., 2007). </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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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Ansley et al. (2003) fragmented the BBS4 gene (600374) into 8 overlapping segments and searched the conceptual translation of the draft human genome and the EST database. In 1 instance they observed an alignment between 3 consecutive TPRs of BBS4 and a contiguous region of the hypothetical protein TTC8. The authors identified 2 alternatively spliced isoforms. RT-PCR analysis of human tissues detected strong expression in testis, ovary, lung, brain, liver, pancreas, and fetal kidney, with lower expression in heart, kidney, placenta, thymus, and spleen. The predicted protein contains 8 C-terminal TPRs and exhibits significant similarity to a prokaryotic domain pilF, involved in twitching mobility and type IV pilus assembly. </p><p>Riazuddin et al. (2010) noted that full-length TTC8 contains 515 amino acids and includes exon 2A, whereas a shorter TTC8 isoform lacking exon 2A contains 505 amino acids. A third isoform lacking exon 2A and exon 5 contains 475 amino acids. RT-PCR analysis of mouse tissues that express Ttc8 detected the Ttc8 isoform containing exon 2A exclusively in retina, and further analysis of mouse retinal tissues obtained by laser-capture microdissection found the exon-2A isoform mostly in the photoreceptor layer. </p><p>Using RT-PCR and mouse knockout models, Murphy et al. (2015) found that full-length Ttc8, including exon 2A, was expressed almost exclusively in retinal photoreceptors. All other mouse tissues expressed Ttc8 transcripts lacking exon 2A. Inclusion of exon 2A in Ttc8 was not detected in developing mouse until postnatal day 0, after which exon 2A inclusion increased rapidly. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ansley et al. (2003) determined that the TTC8 gene contains 14 exons. Subsequently, Riazuddin et al. (2010) identified the retina-specific exon 2A. </p><p>Murphy et al. (2015) identified intronic sequences 5-prime and 3-prime of TTC8 exon 2A that contained retina-specific splicing enhancers for inclusion of exon 2A in photoreceptor cells only. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ansley et al. (2003) stated that the TTC8 gene maps to chromosome 14q32.11. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ansley et al. (2003) found that TTC8 colocalizes with gamma-tubulin (see 191135), BBS4, and PCM1 (600299) in the centrosome. PCM1 is thought to be involved in centriolar replication during ciliogenesis (Kubo et al., 1999). Immunoprecipitation indicated that TTC8 binds to the C terminus of PCM1. A polyclonal antibody against TTC8 stained ciliated structures in 12-day-old mice, including maturing spermatids, the connecting cilium of the retina, and bronchial epithelial cells. In mouse embryos at 14 and 16 days, Ansley et al. (2003) detected specific localization in the telencephalon, with prominent staining at the developing ependymal cell layer and olfactory epithelium. Ansley et al. (2003) found that all C. elegans BBS homologs studied are expressed exclusively in ciliated neurons and contain regulatory elements for RFX, a transcription factor that modulates expression of genes associated with ciliogenesis and intraflagellar transport. </p><p>Nachury et al. (2007) found that BBS1 (209901), BBS2 (606151), BBS4, BBS5 (603650), BBS7 (607590), BBS8, and BBS9 (607968) copurified in stoichiometric amounts from human retinal pigment epithelium (RPE) cells and from mouse testis. PCM1 and alpha-tubulin (see 602529)/beta-tubulin (191130) copurified in substoichiometric amounts. The apparent molecular mass of the complex, which Nachury et al. (2007) called the BBSome, was 438 kD, and it had a sedimentation coefficient of 14S. The complex localized with PCM1 to nonmembranous centriolar satellites in the cytoplasm and, in the absence of PCM1, to the ciliary membrane. Cotransfection and immunoprecipitation experiments suggested that BBS9 was the complex-organizing subunit and that BBS5 mediated binding to phospholipids, predominantly phosphatidylinositol 3-phosphate. BBS1 mediated interaction with RABIN8 (RAB3IP; 608686), the guanine nucleotide exchange factor for the small G protein RAB8 (RAB8A; 165040). Nachury et al. (2007) found that RAB8 promoted ciliary membrane growth through fusion of exocytic vesicles to the base of the ciliary membrane. They concluded that BBS proteins likely function in membrane trafficking to the primary cilium. </p><p>Loktev et al. (2008) found that BBIP10 (613605) copurified and cosedimented with the BBS protein complex from RPE cells. Knockdown of BBIP10 in RPE cells via small interfering RNA compromised assembly of the BBS protein complex and caused failure of ciliogenesis. Knockdown of BBS1, BBS5, or PCM1 resulted in a similar failure of ciliogenesis in RPE cells. Depletion of BBIP10 or BBS8 increased the frequency of centrosome splitting in interphase cells. BBIP10 also had roles in cytoplasmic microtubule stabilization and acetylation that appeared to be independent of its role in assembly of the BBS protein complex. </p><p>Using a protein pull-down assay with homogenized bovine retina, Jin et al. (2010) showed that ARL6 (608845) bound the BBS protein complex. Depletion of ARL6 in human RPE cells did not affect assembly of the complex, but it blocked its localization to cilia. Targeting of ARL6 and the protein complex to cilia required GTP binding by ARL6, but not ARL6 GTPase activity. When in the GTP-bound form, the N-terminal amphipathic helix of ARL6 bound brain lipid liposomes and recruited the BBS protein complex. Upon recruitment, the complex appeared to polymerize into an electron-dense planar coat, and it functioned in lateral transport of test cargo proteins to ciliary membranes. </p><p>By mass spectrometric analysis of transgenic mouse testis, Seo et al. (2011) found that Lxtfl1 (606568) copurified with human BBS4 and with the core mouse BBS complex subunits Bbs1, Bbs2, Bbs5, Bbs7, Bbs8, and Bbs9. Immunohistochemical analysis of human RPE cells showed colocalization of LXTFL1 and BBS9 in cytoplasmic punctae. Use of small interfering RNA revealed distinct functions for each BBS subunit in BBS complex assembly and trafficking. LZTFL1 depletion and overexpression studies showed a negative role for LZTFL1 in BBS complex trafficking, but no effect of LZTFL1 on BBS complex assembly. Mutation analysis revealed that the C-terminal half of Lztfl1 interacted with the C-terminal domain of Bbs9 and that the N-terminal half of Lztfl1 negatively regulated BBS complex trafficking. Depletion of several BBS subunits and LZTFL1 also altered Hedgehog (SHH; 600725) signaling, as measured by GLI1 (165220) expression and ciliary trafficking of SMO (SMOH; 601500). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using computational analysis, Jin et al. (2010) found that the BBS protein complex shares structural features with the canonical coat complexes COPI (601924), COPII (see 610511), and clathrin AP1 (see 603531). BBS4 and BBS8 consist almost entirely of tetratricopeptide repeats (TPRs) (13 and 12.5 TPRs, respectively), which are predicted to fold into extended rod-shaped alpha solenoids. BBS1, BBS2, BBS7, and BBS9 each have an N-terminal beta-propeller fold followed by an amphipathic helical linker and a gamma-adaptin (AP1G1; 603533) ear motif. In BBS2, BBS7, and BBS9, the ear motif is followed by an alpha/beta platform domain and an alpha helix. In BBS1, a 4-helix bundle is inserted between the second and third blades of the beta propeller. BBS5 contains 2 pleckstrin (PLEK; 173570) homology domains and a 3-helix bundle, while BBIP10 consists of 2 alpha helices. Jin et al. (2010) concluded that the abundance of beta propellers, alpha solenoids, and appendage domains inside the BBS protein complex suggests that it shares an evolutionary relationship with canonical coat complexes. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Bardet-Biedl Syndrome 8</em></strong></p><p>
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Ansley et al. (2003) screened the TTC8 gene in a cohort of 120 unrelated patients with Bardet-Biedl syndrome (see BBS8, 615985) and identified homozygous alterations in patients from 3 families. All 8 affected individuals in these 3 families had a homozygous mutant genotype and exhibited classic BBS signs. These mutations were not identified in 192 ethnically matched control chromosomes. One of the affected family members with BBS due to TTC8 mutations demonstrated situs inversus. The association between BBS and the situs inversus phenotype was not coincidental, although the presence of situs in only 1 of 3 affected family members suggested that the defect was one of randomization of left-right symmetry. </p><p>Ansley et al. (2003) demonstrated that BBS is probably caused by a defect of the basal body of ciliated cells. The TTC8 gene, mutations in which are responsible for BBS8, encodes a protein with a prokaryotic domain, pilF, involved in pilus formation and twitching mobility. In 1 family a homozygous null BBS8 mutation (608132.0002) led to BBS with randomization of left-right body axis symmetry, a defect of the nodal cilium. Ansley et al. (2003) showed that TTC8 localizes to centrosomes and basal bodies and colocalizes with gamma-tubulin (see 191135), BBS4 (600374), and PCM1 (600299). Furthermore, Ansley et al. (2003) found that all available C. elegans BBS homologs are expressed exclusively in ciliated neurons and contain regulatory elements for RFX, a transcription factor that modulates the expression of genes associated with ciliogenesis and intraflagellar transport. </p><p>Stoetzel et al. (2006) identified homozygous mutations in the TTC8 gene (608132.0003 and 608132.0004) in 2 of 128 BBS families. One additional family had a heterozygous mutation. Stoetzel et al. (2006) concluded that TTC8 mutations account for only about 2% of BBS families. </p><p><strong><em>Retinitis Pigmentosa 51</em></strong></p><p>
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In a large consanguineous Pakistani family segregating autosomal recessive retinitis pigmentosa (RP51; 613464) mapping to chromosome 14q, Riazuddin et al. (2010) sequenced candidate genes and identified a homozygous splice site mutation in the TTC8 gene (608132.0005) that segregated with disease and was not found in controls. None of the affected individuals had evidence of syndromic disease or any features consistent with BBS. The mutation mapped to the splice acceptor site of exon 2A of the TTC8 gene. RT-PCR analysis of mouse tissues that express Ttc8 detected Ttc8 isoforms containing exon 2A exclusively in retina, and further analysis of mouse retinal tissues obtained by laser-capture microdissection found the exon-2A isoform mostly in the photoreceptor layer. </p><p>In 3 affected individuals from a consanguineous North Indian family with nonsyndromic RP and macular degeneration, Goyal et al. (2016) identified homozygosity for a missense mutation in the TTC8 gene (Q449H; 608132.0006). </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 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 BARDET-BIEDL SYNDROME 8</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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TTC8, 6-BP DEL
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<br />
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SNP: rs587777806,
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ClinVar: RCV000002637
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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 families of Saudi Arabian lineage with Bardet-Biedl syndrome (BBS8; 615985), Ansley et al. (2003) identified homozygosity for a 6-bp in-frame deletion in exon 6 of the TTC8 gene that eliminated 2 amino acids (187-188delEY). Both the E (glu) and Y (tyr) residues at the those locations are conserved in 16 TTC8 homologs. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0002 BARDET-BIEDL SYNDROME 8</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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TTC8, 3-BP DEL
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<br />
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SNP: rs587777807,
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gnomAD: rs587777807,
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ClinVar: RCV000002638, RCV000546783
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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 consanguineous Pakistani family with Bardet-Biedl syndrome (BBS8; 615985), Ansley et al. (2003) identified a homozygous 3-bp deletion that abolished the donor sequence at the splice junction of exon 10 (IVS10+2-4delTGC) in all 3 patients, but not their unaffected sister. The authors predicted this mutation to result in a read-through culminating in an intronic stop codon. RT-PCR detected no TTC8 expression in cultured renal tubular cells and skin fibroblasts from 2 affected sibs, but detected expression in cells from their unaffected sister, who was heterozygous for the mutation, and in a control cell line. One of the affected sibs manifested situs inversus, which was not thought to be coincidental but to represent a defect of randomization of left-right symmetry. </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>.0003 BARDET-BIEDL SYNDROME 8</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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TTC8, THR153THR
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<br />
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SNP: rs119103286,
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gnomAD: rs119103286,
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ClinVar: RCV000002639, RCV000203928, RCV000415339, RCV001074706, RCV001197566, RCV003415630, RCV005007809
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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 3 sibs with Bardet-Biedl syndrome (BBS8; 615985), Stoetzel et al. (2006) identified a homozygous 459G-A transition affecting the last G of exon 4 of the TTC8 gene and predicted to abolish the splice site of exon 4. One affected sib also had a heterozygous mutation in the BBS7 gene (607590), but the authors concluded that it was not pathogenic, since no clinical differences were noted between the sib with the BBS7 mutation and the sibs without the BBS7 mutation. The children were born of consanguineous parents of North African descent. </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>.0004 BARDET-BIEDL SYNDROME 8</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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|
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TTC8, IVS6DS, G-A, +1
|
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<br />
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|
|
SNP: rs587777808,
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|
|
gnomAD: rs587777808,
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|
|
ClinVar: RCV000002640, RCV001699099
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|
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|
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</span>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a child with Bardet-Biedl syndrome (BBS8; 615985), born of consanguineous Lebanese parents, Stoetzel et al. (2006) identified a homozygous G-to-A splice site mutation in intron 6 of the TTC8 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
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<div>
|
|
<br />
|
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</div>
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|
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 RETINITIS PIGMENTOSA 51</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
TTC8, IVS1AS, A-G, -2
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs587777809,
|
|
|
|
|
|
|
|
ClinVar: RCV000002641, RCV004794322
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected members of a large consanguineous Pakistani family segregating autosomal recessive retinitis pigmentosa (RP51; 613464), Riazuddin et al. (2010) identified homozygosity for a -2A-G transition in intron 1 of the TTC8 gene, predicted to result in deletion of 10 amino acids from the protein. The mutation segregated with the disease and was not found in 384 Pakistani control chromosomes or 384 chromosomes of northern European descent. None of the affected individuals had evidence of syndromic disease or any features consistent with BBS. The mutation mapped to a highly conserved splice acceptor site of exon 2A of the TTC8 gene. RT-PCR analysis of mouse tissues that express Ttc8 detected Ttc8 isoforms containing exon 2A exclusively in retina, and further analysis of mouse retinal tissues obtained by laser-capture microdissection found the exon-2A isoform mostly in the photoreceptor layer. </p><p>Using subretinal injection and electroporation of a fluorescent splicing reporter in mice, Murphy et al. (2015) found that the -2A-G transition in intron 1 of the TTC8 gene disrupted the 5-prime splice site of exon 2A and forced the use of a cryptic splice site 7 nucleotides downstream of the mutation. Missplicing of exon 2A in retina resulted in premature termination and elimination of TTC8 protein in photoreceptors. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 RETINITIS PIGMENTOSA 51</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TTC8, GLN449HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs876661403,
|
|
|
|
|
|
gnomAD: rs876661403,
|
|
|
|
|
|
ClinVar: RCV000223936
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected individuals from a consanguineous North Indian family with nonsyndromic RP and macular degeneration (RP51; 613464), Goyal et al. (2016) identified homozygosity for a c.1347G-C transversion (c.1347G-C, NM_144596.3) in exon 13 of the TTC8 gene, resulting in a gln449-to-his (Q449H) substitution at a highly conserved residue. The mutation segregated with disease in the family and was not found in 100 ethnically matched controls. The authors noted that the mutation involved the last nucleotide of exon 13, thereby affecting the 5-prime splice site consensus sequence; however, RNA was not available to test the effects of the mutation on splicing. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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|
</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
|
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<p class="mim-text-font">
|
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Ansley, S. J., Badano, J. L., Blacque, O. E., Hill, J., Hoskins, B. E., Leitch, C. C., Kim, J. C., Ross, A. J., Eichers, E. R., Teslovich, T. M., Mah, A. K., Johnsen, R. C., Cavender, J. C., Lewis, R. A., Leroux, M. R., Beales, P. L., Katsanis, N.
|
|
<strong>Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.</strong>
|
|
Nature 425: 628-633, 2003.
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[PubMed: 14520415]
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[Full Text: https://doi.org/10.1038/nature02030]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Goyal, S., Jager, M., Robinson, P. N., Vanita, V.
|
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<strong>Confirmation of TTC8 as a disease gene for nonsyndromic autosomal recessive retinitis pigmentosa (RP51).</strong>
|
|
Clin. Genet. 89: 454-460, 2016.
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[PubMed: 26195043]
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[Full Text: https://doi.org/10.1111/cge.12644]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Jin, H., White, S. R., Shida, T., Schulz, S., Aguiar, M., Gygi, S. P., Bazan, J. F., Nachury, M. V.
|
|
<strong>The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia.</strong>
|
|
Cell 141: 1208-1219, 2010.
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[PubMed: 20603001]
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[Full Text: https://doi.org/10.1016/j.cell.2010.05.015]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Kubo, A., Sasaki, H., Yuba-Kubo, A., Tsukita, S., Shiina, N.
|
|
<strong>Centriolar satellites: molecular characterization, ATP-dependent movement toward centrioles and possible involvement in ciliogenesis.</strong>
|
|
J. Cell Biol. 147: 969-979, 1999. Note: Erratum: J. Cell Biol. 147: 1585 only, 1999.
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[PubMed: 10579718]
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[Full Text: https://doi.org/10.1083/jcb.147.5.969]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Loktev, A. V., Zhang, Q., Beck, J. S., Searby, C. C., Scheetz, T. E., Bazan, J. F., Slusarski, D. C., Sheffield, V. C., Jackson, P. K., Nachury, M. V.
|
|
<strong>A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.</strong>
|
|
Dev. Cell 15: 854-865, 2008.
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[PubMed: 19081074]
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[Full Text: https://doi.org/10.1016/j.devcel.2008.11.001]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Murphy, D., Singh, R., Kolandaivelu, S., Ramamurthy, V., Stoilov, P.
|
|
<strong>Alternative splicing shapes the phenotype of a mutation in BBS8 to cause nonsyndromic retinitis pigmentosa.</strong>
|
|
Molec. Cell. Biol. 35: 1860-1870, 2015.
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[PubMed: 25776555]
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[Full Text: https://doi.org/10.1128/MCB.00040-15]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peranen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C., Jackson, P. K.
|
|
<strong>A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.</strong>
|
|
Cell 129: 1201-1213, 2007.
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[PubMed: 17574030]
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[Full Text: https://doi.org/10.1016/j.cell.2007.03.053]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Riazuddin, S. A., Iqbal, M., Wang, Y., Masuda, T., Chen, Y., Bowne, S., Sullivan, L. S., Waseem, N. H., Bhattacharya, S., Daiger, S. P., Zhang, K., Khan, S. N., Riazuddin, S., Hejtmancik, J. F., Sieving, P. A., Zack, D. J., Katsanis, N.
|
|
<strong>A splice-site mutation in a retina-specific exon of BBS8 causes nonsyndromic retinitis pigmentosa.</strong>
|
|
Am. J. Hum. Genet. 86: 805-812, 2010.
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[PubMed: 20451172]
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[Full Text: https://doi.org/10.1016/j.ajhg.2010.04.001]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Seo, S., Zhang, Q., Bugge, K., Breslow, D. K., Searby, C. C., Nachury, M. V., Sheffield, V. C.
|
|
<strong>A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.</strong>
|
|
PLoS Genet. 7: e1002358, 2011. Note: Electronic Article.
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[PubMed: 22072986]
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[Full Text: https://doi.org/10.1371/journal.pgen.1002358]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Stoetzel, C., Laurier, V., Faivre, L., Megarbane, A., Perrin-Schmitt, F., Verloes, A., Bonneau, D., Mandel, J.-L., Cossee, M., Dollfus, H.
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<strong>BBS8 is rarely mutated in a cohort of 128 Bardet-Biedl syndrome families.</strong>
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J. Hum. Genet. 51: 81-84, 2006.
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[PubMed: 16308660]
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[Full Text: https://doi.org/10.1007/s10038-005-0320-2]
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Patricia A. Hartz - updated : 6/2/2016<br>Marla J. F. O'Neill - updated : 5/31/2016<br>Patricia A. Hartz - updated : 11/12/2012<br>Patricia A. Hartz - updated : 10/13/2010<br>Marla J. F. O'Neill - updated : 6/21/2010<br>Cassandra L. Kniffin - updated : 3/2/2006
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