3441 lines
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- *120260 - COLLAGEN, TYPE IX, ALPHA-2; COL9A2
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- OMIM
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<p>
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<span class="h4">*120260</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/120260">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000049089;t=ENST00000372748" 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=1298" 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=120260" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000049089;t=ENST00000372748" 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_001852,XM_011540715,XM_011540716,XM_017000332,XM_017000333,XM_047446392" 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_001852" 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=120260" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=00373&isoform_id=00373_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/COL9A2" 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/1054873,3510460,11386161,20137328,119627629,119627630,119627631,119627632,119627633,119627634,119627635,119627636,119627637,187950331,187952367,767902448,767902450,1034555618,1034555623,2217264125,2462503978,2462503980,2462503982,2462503984,2462503986" 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/Q14055" 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=1298" 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=ENSG00000049089;t=ENST00000372748" 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=COL9A2" 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=COL9A2" 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+1298" 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/COL9A2" 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:1298" 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/1298" 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=chr1&hgg_gene=ENST00000372748.8&hgg_start=40300489&hgg_end=40317286&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:2218" 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:2218" 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=120260[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=120260[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/COL9A2/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/ENSG00000049089" 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=COL9A2" 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=COL9A2" 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=COL9A2" 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=COL9A2&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/PA26734" 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:2218" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:88466" 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/COL9A2#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:88466" 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/1298/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/OMIA001523/" 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=1298" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000708;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000708 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000752;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000752 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-9786" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1298" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=COL9A2&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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120260
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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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COLLAGEN, TYPE IX, ALPHA-2; COL9A2
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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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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=COL9A2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">COL9A2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/1/487?start=-3&limit=10&highlight=487">1p34.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:40300489-40317286&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'})">1:40,300,489-40,317,286</a> </span>
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</em>
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
|
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<th>
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|
Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=614284,600204" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
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</th>
|
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/487?start=-3&limit=10&highlight=487">
|
|
1p34.2
|
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</a>
|
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</span>
|
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</td>
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
?Stickler syndrome, type V
|
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<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>
|
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</span>
|
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
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|
<a href="/entry/614284"> 614284 </a>
|
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Epiphyseal dysplasia, multiple, 2
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/600204"> 600204 </a>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
|
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<p>The COL9A2 gene encodes the alpha-2 subunit of collagen type IX. Type IX collagen, a heterotrimer of alpha-1 (COL9A1; <a href="/entry/120210">120210</a>), alpha-2, and alpha-3 (COL9A3; <a href="/entry/120270">120270</a>) chains specific for this type of collagen, is a cartilage-specific fibril-associated collagen (<a href="#11" class="mim-tip-reference" title="Perala, M., Hanninen, M., Hastbacka, J., Elima, K., Vuorio, E. <strong>Molecular cloning of the human alpha-2(IX) collagen cDNA and assignment of the human COL9A2 gene to chromosome 1.</strong> FEBS Lett. 319: 177-180, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8454052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8454052</a>] [<a href="https://doi.org/10.1016/0014-5793(93)80062-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8454052">Perala et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8454052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the process of characterizing genomic clones for the mouse COL9A2 gene, <a href="#11" class="mim-tip-reference" title="Perala, M., Hanninen, M., Hastbacka, J., Elima, K., Vuorio, E. <strong>Molecular cloning of the human alpha-2(IX) collagen cDNA and assignment of the human COL9A2 gene to chromosome 1.</strong> FEBS Lett. 319: 177-180, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8454052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8454052</a>] [<a href="https://doi.org/10.1016/0014-5793(93)80062-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8454052">Perala et al. (1993)</a> also used 4 pairs of oligonucleotide primers designed for amplification of murine exon sequences to construct cDNA clones for the human gene spanning more than 90% of the coding region. The amino acid and nucleotide sequence identities between human and chick are 78 and 71%, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8454052" 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="#11" class="mim-tip-reference" title="Perala, M., Hanninen, M., Hastbacka, J., Elima, K., Vuorio, E. <strong>Molecular cloning of the human alpha-2(IX) collagen cDNA and assignment of the human COL9A2 gene to chromosome 1.</strong> FEBS Lett. 319: 177-180, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8454052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8454052</a>] [<a href="https://doi.org/10.1016/0014-5793(93)80062-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8454052">Perala et al. (1993)</a> assigned the human COL9A2 gene to chromosome 1 by study of a panel of DNAs from human/rodent somatic cell hybrids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8454052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Warman, M. L., McCarthy, M. T., Perala, M., Vuorio, E., Knoll, J. H. M., McDaniels, C. N., Mayne, R., Beier, D. R., Olsen, B. R. <strong>The genes encoding alpha-2(IX) collagen (COL9A2) map to human chromosome 1p32.3-p33 and mouse chromosome 4.</strong> Genomics 23: 158-162, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7829066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7829066</a>] [<a href="https://doi.org/10.1006/geno.1994.1472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7829066">Warman et al. (1994)</a> used fluorescence in situ hybridization to regionalize the COL9A2 gene to 1p33-p32.3. A single-strand conformation polymorphism within the murine gene was used to map Col9a2 to mouse chromosome 4. Since one form of multiple epiphyseal dysplasia (EDM2; <a href="/entry/600204">600204</a>) maps to the same region of chromosome 1, COL9A2 was considered to be a candidate gene for that disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7829066" 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="Hellsten, E., Vesa, J., Heiskanen, M., Makela, T. P., Jarvela, I., Cowell, J. K., Mead, S., Alitalo, K., Palotie, A., Peltonen, L. <strong>Identification of YAC clones for human chromosome 1p32 and physical mapping of the infantile neuronal ceroid lipofuscinosis (INCL) locus.</strong> Genomics 25: 404-412, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789974</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80040-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789974">Hellsten et al. (1995)</a> demonstrated that the COL9A2 gene is in a 1-Mb contig, proximal to RLF (<a href="/entry/180610">180610</a>) and MYCL1 (<a href="/entry/164850">164850</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789974" 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="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 7/13/2017."None>Gross (2017)</a> mapped the COL9A2 gene to chromosome 1p34.2 based on an alignment of the COL9A2 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF019406" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF019406</a>) with the genomic sequence (GRCh38).</p>
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<p>The cartilage collagen fibrils are formed from fibrillar collagens II and XI (<a href="/entry/120280">120280</a>), while collagen IX is located on the fibril surface (see Figure 2 in <a href="#9" class="mim-tip-reference" title="Muragaki, Y., Mariman, E. C. M., van Beersum, S. E. C., Perala, M., van Mourik, J. B. A., Warman, M. L., Olsen, B. R., Hamel, B. C. J. <strong>A mutation in the gene encoding the alpha-2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2).</strong> Nature Genet. 12: 103-105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528240</a>] [<a href="https://doi.org/10.1038/ng0196-103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528240">Muragaki et al., 1996</a>). The alpha-1(IX) chain contains a large N-terminal globular domain (NC4); a chondroitin sulfate chain is attached to the alpha-2(IX) chain (<a href="#9" class="mim-tip-reference" title="Muragaki, Y., Mariman, E. C. M., van Beersum, S. E. C., Perala, M., van Mourik, J. B. A., Warman, M. L., Olsen, B. R., Hamel, B. C. J. <strong>A mutation in the gene encoding the alpha-2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2).</strong> Nature Genet. 12: 103-105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528240</a>] [<a href="https://doi.org/10.1038/ng0196-103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528240">Muragaki et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528240" 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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The usefulness of the candidate gene approach for identification of a basic gene defect was illustrated by the finding of a mutation in the COL9A2 gene (<a href="#0001">120260.0001</a>) in a Dutch kindred with multiple epiphyseal dysplasia-2 (EDM2; <a href="/entry/600204">600204</a>) showing linkage to DNA markers in the region of 1p32 (<a href="#9" class="mim-tip-reference" title="Muragaki, Y., Mariman, E. C. M., van Beersum, S. E. C., Perala, M., van Mourik, J. B. A., Warman, M. L., Olsen, B. R., Hamel, B. C. J. <strong>A mutation in the gene encoding the alpha-2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2).</strong> Nature Genet. 12: 103-105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528240</a>] [<a href="https://doi.org/10.1038/ng0196-103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528240">Muragaki et al., 1996</a>). <a href="#9" class="mim-tip-reference" title="Muragaki, Y., Mariman, E. C. M., van Beersum, S. E. C., Perala, M., van Mourik, J. B. A., Warman, M. L., Olsen, B. R., Hamel, B. C. J. <strong>A mutation in the gene encoding the alpha-2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2).</strong> Nature Genet. 12: 103-105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528240</a>] [<a href="https://doi.org/10.1038/ng0196-103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528240">Muragaki et al. (1996)</a> stated that the results provided by the EDM2 'experiment of nature' represent the first in vivo evidence for the role of collagen IX in human articular cartilage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528240" 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="Holden, P., Canty, E. G., Mortier, G. R., Zabel, B., Spranger, J., Carr, A., Grant, M. E., Loughlin, J. A., Briggs, M. D. <strong>Identification of novel pro-alpha-2(IX) collagen gene mutations in two families with distinctive oligo-epiphyseal forms of multiple epiphyseal dysplasia.</strong> Am. J. Hum. Genet. 65: 31-38, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364514</a>] [<a href="https://doi.org/10.1086/302440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364514">Holden et al. (1999)</a> described 2 families with distinctive oligoepiphyseal forms of multiple epiphyseal dysplasia, in which heterozygosity for different mutations in the COL9A2 gene (<a href="#0002">120260.0002</a> and <a href="#0003">120260.0003</a>) was found. Both of these mutations resulted in the skipping of exon 3 from the COL9A2 mRNA, but the position of the mutation in the splice donor site determined the stability of the mRNA produced from the mutant allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10364514" 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>Stickler Syndrome V</em></strong></p><p>
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In a large 5-generation consanguineous pedigree of Asian Indian origin segregating autosomal recessive Stickler syndrome (STL5; <a href="/entry/614284">614284</a>), <a href="#2" class="mim-tip-reference" title="Baker, S., Booth, C., Fillman, C., Shapiro, M., Blair, M. P., Hyland, J. C., Ala-Kokko, L. <strong>A loss of function mutation in the COL9A2 gene cause autosomal recessive Stickler syndrome.</strong> Am. J. Med. Genet. 155A: 1668-1672, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21671392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21671392</a>] [<a href="https://doi.org/10.1002/ajmg.a.34071" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21671392">Baker et al. (2011)</a> analyzed 3 candidate collagen IX-related genes and identified homozygosity for an 8-bp deletion in the COL9A2 gene (<a href="#0006">120260.0006</a>) that segregated with disease in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21671392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between intervertebral disc disease (IDD; <a href="/entry/603932">603932</a>) and variation in the COL9A2 gene, see <a href="#0004">120260.0004</a>.</p>
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<p>In a canine model of oculoskeletal dysplasia in Samoyed dogs, termed drd2 (dwarfism with retinal dysplasia type 2), <a href="#4" class="mim-tip-reference" title="Goldstein, O., Guyon, R., Kukekova, A., Kuznetsova, T. N., Pearce-Kelling, S. E., Johnson, J., Aguirre, G. D., Acland, G. M. <strong>COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia.</strong> Mammalian Genome 21: 398-408, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20686772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20686772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20686772[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/10.1007/s00335-010-9276-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20686772">Goldstein et al. (2010)</a> identified a homozygous 1,267-bp deletion in the 5-prime end of the COL9A2 gene that segregated with the phenotype. The mutation affected the COL3 domain of the gene. Northern blot analysis showed reduced RNA expression of the COL9A2 gene in affected retinas. The drd2 phenotype is characterized by short-limb dwarfism and severe ocular defects, such as vitreous dysplasia, retinal detachment, and cataracts. Heterozygous carrier dogs may exhibit a milder ocular phenotype, such as vitreal strands or retinal dysplasia, but have a normal appendicular skeleton. <a href="#4" class="mim-tip-reference" title="Goldstein, O., Guyon, R., Kukekova, A., Kuznetsova, T. N., Pearce-Kelling, S. E., Johnson, J., Aguirre, G. D., Acland, G. M. <strong>COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia.</strong> Mammalian Genome 21: 398-408, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20686772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20686772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20686772[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/10.1007/s00335-010-9276-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20686772">Goldstein et al. (2010)</a> noted that the drd2 phenotype resembles human hereditary arthroophthalmopathies such as Stickler syndrome, Kniest dysplasia (<a href="/entry/156550">156550</a>), and Marshall syndrome (<a href="/entry/154780">154780</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20686772" 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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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=120260[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">rs1569763139 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569763139;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=rs1569763139" 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=rs1569763139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#9" class="mim-tip-reference" title="Muragaki, Y., Mariman, E. C. M., van Beersum, S. E. C., Perala, M., van Mourik, J. B. A., Warman, M. L., Olsen, B. R., Hamel, B. C. J. <strong>A mutation in the gene encoding the alpha-2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2).</strong> Nature Genet. 12: 103-105, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528240</a>] [<a href="https://doi.org/10.1038/ng0196-103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528240">Muragaki et al. (1996)</a> demonstrated a mutation in affected members of a family with multiple epiphyseal dysplasia (EDM2; <a href="/entry/600204">600204</a>) that showed linkage to the 1p32 region. Affected members were heterozygous for a splice site mutation causing exon skipping during RNA splicing and an in-frame loss of 12 amino acids within the alpha-2 (IX) collagen chain. The results provided the first in vivo evidence for the role of collagen IX in human articular cartilage. The clinical findings in the family were entirely characteristic of MED although hip complaints were less conspicuous than in many kindreds. The specific mutation was a T-to-C transition in the consensus donor splice site of intron 3, resulting in the skipping of exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528240" 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="Jackson, G. C., Marcus-Soekarman, D., Stolte-Dijkstra, I., Verrips, A., Taylor, J. A., Briggs, M. D. <strong>Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.</strong> Am. J. Med. Genet. 152A: 863-869, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20358595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.33240" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20358595">Jackson et al. (2010)</a> reported a large 4-generation family with autosomal dominant transmission of EDM2 associated with the T-to-C transition in intron 3 (186+2T-C) of the COL9A2 gene. The family had previously been reported by <a href="#12" class="mim-tip-reference" title="Versteylen, R. J., Zwemmer, A., Lorie, C. A. M., Schuur, K. H. <strong>Multiple epiphyseal dysplasia complicated by severe osteochondritis dissecans of the knee: incidence in two families.</strong> Skeletal Radiol. 17: 407-412, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3238439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3238439</a>] [<a href="https://doi.org/10.1007/BF00361659" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3238439">Versteylen et al. (1988)</a>. The proband was a 33-year-old woman with short stature who complained of stiff and painful hands and knees since age 4 years. Radiographs of the knees showed Blount disease (progressive varus deformity of the proximal tibia associated with internal torsion of the tibia) and of the spine showed mild spondyloarthrotic abnormalities in the thoracic region. Her sister had painful and swollen knees since age 4 years and developed severe osteochondritis dissecans as an adult. Two sons of the proband were also affected, showing pain in the knees during walking and clumsy walking. These boys also had frontal bossing, depressed nasal bridge, and were easily fatigued with mild muscle weakness. Radiographs of 1 son at age 3 years showed delayed ossification of the epiphyses, small proximal femoral epiphyses, and small femoral and tibial epiphyses around the knees. Skeletal muscle biopsy and mitochondrial studies showed no significant abnormalities, only mild variations in fiber size and slightly diminished ATP production. <a href="#8" class="mim-tip-reference" title="Jackson, G. C., Marcus-Soekarman, D., Stolte-Dijkstra, I., Verrips, A., Taylor, J. A., Briggs, M. D. <strong>Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.</strong> Am. J. Med. Genet. 152A: 863-869, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20358595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.33240" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20358595">Jackson et al. (2010)</a> commented on the mild myopathy present in the boys, and noted that EDM is characterized by clinical variability even within the same family. The mild myopathic and mitochondrial changes observed may be secondary to a tendinopathy and/or cell stress response resulting from expression of mutant collagen. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20358595+3238439" 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> rs1085307973 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1085307973;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/rs1085307973?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=rs1085307973" 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=rs1085307973" 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=RCV000489270 OR RCV001807641 OR RCV004740263" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000489270, RCV001807641, RCV004740263" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000489270...</a>
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<p>In family K of <a href="#7" class="mim-tip-reference" title="Holden, P., Canty, E. G., Mortier, G. R., Zabel, B., Spranger, J., Carr, A., Grant, M. E., Loughlin, J. A., Briggs, M. D. <strong>Identification of novel pro-alpha-2(IX) collagen gene mutations in two families with distinctive oligo-epiphyseal forms of multiple epiphyseal dysplasia.</strong> Am. J. Hum. Genet. 65: 31-38, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364514</a>] [<a href="https://doi.org/10.1086/302440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364514">Holden et al. (1999)</a> with multiple epiphyseal dysplasia-2 (EDM2; <a href="/entry/600204">600204</a>), the proband was a 17-year-old male of normal height who was diagnosed in childhood with pain in the joints, mostly the knees, and genu varum. Radiographs showed major epiphyseal changes in the knees and hands, and almost no changes in the hips. The spine also appeared normal. The molecular change was a G-to-A transition in the last nucleotide of exon 3, changing the last codon of exon 3 from CCG (pro) to CCA (also pro). Although there was no change in the amino acid, the change interfered with splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10364514" 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="Nakashima, E., Ikegawa, S., Ohashi, H., Kimizuka, M., Nishimura, G. <strong>Double-layered patella in multiple epiphyseal dysplasia is not exclusive to DTDST mutation. (Letter)</strong> Am. J. Med. Genet. 133A: 106-107, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15633184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15633184</a>] [<a href="https://doi.org/10.1002/ajmg.a.30481" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15633184">Nakashima et al. (2005)</a> identified the exon 3 G-to-A transition in the COL9A2 gene in affected members of a Japanese family with EDM2. The proband had bilateral double-layered patellae, indicating that this unusual feature is not unique to autosomal recessive multiple epiphyseal dysplasia with homozygous mutations in the DTDST gene (<a href="/entry/606718">606718</a>; see EDM4 <a href="/entry/226900">226900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15633184" 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="Jackson, G. C., Marcus-Soekarman, D., Stolte-Dijkstra, I., Verrips, A., Taylor, J. A., Briggs, M. D. <strong>Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.</strong> Am. J. Med. Genet. 152A: 863-869, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20358595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.33240" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20358595">Jackson et al. (2010)</a> reported a patient with EDM2 characterized by onset at age 3 years of an abnormal gait associated with proximal muscle weakness. He had left-sided developmental dysplasia of the hip. The family history was positive for hypodontia and for osteochondritis dissecans. However, 2 affected adult family members showed improvement of the disorder after puberty. The proband was heterozygous for the 186G-A transition in the splice donor sequence of exon 3 of the COL9A2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20358595" 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">rs1569763108 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569763108;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=rs1569763108" 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=rs1569763108" 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=RCV000018682 OR RCV005089274" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018682, RCV005089274" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018682...</a>
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<p>Family G reported by <a href="#7" class="mim-tip-reference" title="Holden, P., Canty, E. G., Mortier, G. R., Zabel, B., Spranger, J., Carr, A., Grant, M. E., Loughlin, J. A., Briggs, M. D. <strong>Identification of novel pro-alpha-2(IX) collagen gene mutations in two families with distinctive oligo-epiphyseal forms of multiple epiphyseal dysplasia.</strong> Am. J. Hum. Genet. 65: 31-38, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364514</a>] [<a href="https://doi.org/10.1086/302440" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364514">Holden et al. (1999)</a> with an oligoepiphyseal form of multiple epiphyseal dysplasia (EDM2; <a href="/entry/600204">600204</a>) and a mutation in the COL9A2 gene had affected members in 4 generations, of whom a mother and her 2 sons were available for study. They were slightly short in stature (adult height, 158 cm), and all 3 developed genu valgum, which required surgical correction. The mother started walking late and with a stiff gait that became more noticeable during ages 5 to 7 years. Her legs became increasingly bowed, and at age 17 she underwent tibial osteotomy. She had developed increasing problems with pain in her hands, lumbar spine, and ankles. Her 2 sons walked at age 2 years with a stiff gait. Epiphyseal dysplasia was recognized in them in early childhood, and they underwent tibial osteotomy for genu valgum at ages 14 and 13, respectively. They continued to have mild joint symptoms, including intermittent lumbar back pain and knee pain with swelling. Changes were not found clinically or radiographically in the hips. Affected members showed heterozygosity for a G-to-C transversion at position +5 of intron 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10364514" 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">rs137853213 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853213;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=rs137853213" 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=rs137853213" 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=RCV000018683 OR RCV000710925" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018683, RCV000710925" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018683...</a>
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<p>This variant, formerly titled INTERVERTEBRAL DISC DISEASE, SUSCEPTIBILITY TO, has been reclassified because its contribution to the disorder has not been confirmed.</p><p>In a study that examined for allelic variation in the COL9A2 gene in Finnish individuals with sciatica and radiologically documented intervertebral disc disease (IDD; <a href="/entry/603932">603932</a>), <a href="#1" class="mim-tip-reference" title="Annunen, S., Paassilta, P. Lohiniva, J., Perala, M., Pihlajamaa, T., Karppinen, J., Tervonen, O., Kroger, H., Lahde, S., Vanharanta, H., Ryhanen, L., Goring, H. H. H., Ott, J., Prockop, D. J., Ala-Kokko, L. <strong>An allele of COL9A2 associated with intervertebral disc disease.</strong> Science 285: 409-412, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10411504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10411504</a>] [<a href="https://doi.org/10.1126/science.285.5426.409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10411504">Annunen et al. (1999)</a> found a substitution of tryptophan for glutamine at codon 326. This change was found in 6 of 157 individuals with disc disease but in none of 174 controls. Further analysis of the families of 4 of the original patients revealed that all individuals heterozygous for the trp substitution demonstrated the disease phenotype. Many individuals within these families had IDD but not the trp allele. The authors invoked a high phenocopy rate to reconcile this observation with the conclusion that this sequence variant within COL9A2 contributes to the pathogenesis of disease. In the disease model chosen, this locus accounted for 10% of disease prevalence. Under these constraints, <a href="#1" class="mim-tip-reference" title="Annunen, S., Paassilta, P. Lohiniva, J., Perala, M., Pihlajamaa, T., Karppinen, J., Tervonen, O., Kroger, H., Lahde, S., Vanharanta, H., Ryhanen, L., Goring, H. H. H., Ott, J., Prockop, D. J., Ala-Kokko, L. <strong>An allele of COL9A2 associated with intervertebral disc disease.</strong> Science 285: 409-412, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10411504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10411504</a>] [<a href="https://doi.org/10.1126/science.285.5426.409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10411504">Annunen et al. (1999)</a> demonstrated a lod score of 4.5 at a recombination fraction of 0.12. Subsequent linkage disequilibrium analysis conditional on linkage gave an additional lod score of 7.1. The authors did not exclude the possibility that a true disease locus may lie in close physical proximity to COL9A2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10411504" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 EPIPHYSEAL DYSPLASIA, MULTIPLE, 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1085307973 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1085307973;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/rs1085307973?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=rs1085307973" 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=rs1085307973" 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=RCV000018684 OR RCV001851921" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018684, RCV001851921" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018684...</a>
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<p>In 12 affected members from a 4-generation family with a relatively hip-sparing multiple epiphyseal dysplasia phenotype (EDM2; <a href="/entry/600204">600204</a>), <a href="#3" class="mim-tip-reference" title="Fiedler, J., Stove, J., Heber, F., Brenner, R. E. <strong>Clinical phenotype and molecular diagnosis of multiple epiphyseal dysplasia with relative hip sparing during childhood (EDM2).</strong> Am. J. Med. Genet. 112: 144-153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12244547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12244547</a>] [<a href="https://doi.org/10.1002/ajmg.10554" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12244547">Fiedler et al. (2002)</a> identified a G-to-C mutation in the last nucleotide of exon 3 of the COL9A2 gene. The disorder was characterized by childhood onset of pain and stiffness in the knees. Finger joints, ankles, and elbows became symptomatic during early adult life. Some adult patients had free articular bodies which resulted in locking of the joints. <a href="#3" class="mim-tip-reference" title="Fiedler, J., Stove, J., Heber, F., Brenner, R. E. <strong>Clinical phenotype and molecular diagnosis of multiple epiphyseal dysplasia with relative hip sparing during childhood (EDM2).</strong> Am. J. Med. Genet. 112: 144-153, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12244547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12244547</a>] [<a href="https://doi.org/10.1002/ajmg.10554" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12244547">Fiedler et al. (2002)</a> noted that a G-to-A change at the same nucleotide had earlier been found to cause EDM2 (<a href="#0002">120260.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12244547" 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 STICKLER SYNDROME V (1 family)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs606231376 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs606231376;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=rs606231376" 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=rs606231376" 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=RCV000022493" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022493" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022493</a>
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<p>In an affected sister and brother from a large 5-generation consanguineous pedigree of Asian Indian origin segregating autosomal recessive Stickler syndrome (STL5; <a href="/entry/614284">614284</a>), <a href="#2" class="mim-tip-reference" title="Baker, S., Booth, C., Fillman, C., Shapiro, M., Blair, M. P., Hyland, J. C., Ala-Kokko, L. <strong>A loss of function mutation in the COL9A2 gene cause autosomal recessive Stickler syndrome.</strong> Am. J. Med. Genet. 155A: 1668-1672, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21671392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21671392</a>] [<a href="https://doi.org/10.1002/ajmg.a.34071" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21671392">Baker et al. (2011)</a> identified homozygosity for an 8-bp deletion in the COL9A2 gene involving the last 4 nucleotides of exon 16 and the first 4 nucleotides of IVS16 (843_846+4del8). The deletion was predicted to cause a frameshift and downstream premature termination codon (Asp281GlnfsTer70). The mutation was detected in heterozygosity in the sibs' unaffected brother and parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21671392" 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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Annunen, S., Paassilta, P. Lohiniva, J., Perala, M., Pihlajamaa, T., Karppinen, J., Tervonen, O., Kroger, H., Lahde, S., Vanharanta, H., Ryhanen, L., Goring, H. H. H., Ott, J., Prockop, D. J., Ala-Kokko, L.
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<strong>An allele of COL9A2 associated with intervertebral disc disease.</strong>
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Science 285: 409-412, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10411504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10411504</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10411504" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Baker, S., Booth, C., Fillman, C., Shapiro, M., Blair, M. P., Hyland, J. C., Ala-Kokko, L.
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<strong>A loss of function mutation in the COL9A2 gene cause autosomal recessive Stickler syndrome.</strong>
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Am. J. Med. Genet. 155A: 1668-1672, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21671392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21671392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21671392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.34071" target="_blank">Full Text</a>]
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Fiedler, J., Stove, J., Heber, F., Brenner, R. E.
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<strong>Clinical phenotype and molecular diagnosis of multiple epiphyseal dysplasia with relative hip sparing during childhood (EDM2).</strong>
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Am. J. Med. Genet. 112: 144-153, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12244547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12244547</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12244547" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Goldstein, O., Guyon, R., Kukekova, A., Kuznetsova, T. N., Pearce-Kelling, S. E., Johnson, J., Aguirre, G. D., Acland, G. M.
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<strong>COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia.</strong>
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Mammalian Genome 21: 398-408, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20686772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20686772</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20686772[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=20686772" 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/s00335-010-9276-4" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Gross2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Gross, M. B.
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|
<strong>Personal Communication.</strong>
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|
Baltimore, Md. 7/13/2017.
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</p>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Hellsten1995" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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Hellsten, E., Vesa, J., Heiskanen, M., Makela, T. P., Jarvela, I., Cowell, J. K., Mead, S., Alitalo, K., Palotie, A., Peltonen, L.
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<strong>Identification of YAC clones for human chromosome 1p32 and physical mapping of the infantile neuronal ceroid lipofuscinosis (INCL) locus.</strong>
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Genomics 25: 404-412, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789974</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789974" 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/10.1016/0888-7543(95)80040-s" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Holden1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Holden, P., Canty, E. G., Mortier, G. R., Zabel, B., Spranger, J., Carr, A., Grant, M. E., Loughlin, J. A., Briggs, M. D.
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|
<strong>Identification of novel pro-alpha-2(IX) collagen gene mutations in two families with distinctive oligo-epiphyseal forms of multiple epiphyseal dysplasia.</strong>
|
|
Am. J. Hum. Genet. 65: 31-38, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364514</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10364514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/302440" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Jackson2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Jackson, G. C., Marcus-Soekarman, D., Stolte-Dijkstra, I., Verrips, A., Taylor, J. A., Briggs, M. D.
|
|
<strong>Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.</strong>
|
|
Am. J. Med. Genet. 152A: 863-869, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20358595[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=20358595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.33240" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Muragaki1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Muragaki, Y., Mariman, E. C. M., van Beersum, S. E. C., Perala, M., van Mourik, J. B. A., Warman, M. L., Olsen, B. R., Hamel, B. C. J.
|
|
<strong>A mutation in the gene encoding the alpha-2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2).</strong>
|
|
Nature Genet. 12: 103-105, 1996.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528240" 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/ng0196-103" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Nakashima2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nakashima, E., Ikegawa, S., Ohashi, H., Kimizuka, M., Nishimura, G.
|
|
<strong>Double-layered patella in multiple epiphyseal dysplasia is not exclusive to DTDST mutation. (Letter)</strong>
|
|
Am. J. Med. Genet. 133A: 106-107, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15633184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15633184</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15633184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30481" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Perala1993" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
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Perala, M., Hanninen, M., Hastbacka, J., Elima, K., Vuorio, E.
|
|
<strong>Molecular cloning of the human alpha-2(IX) collagen cDNA and assignment of the human COL9A2 gene to chromosome 1.</strong>
|
|
FEBS Lett. 319: 177-180, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8454052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8454052</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8454052" 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/10.1016/0014-5793(93)80062-y" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Versteylen1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Versteylen, R. J., Zwemmer, A., Lorie, C. A. M., Schuur, K. H.
|
|
<strong>Multiple epiphyseal dysplasia complicated by severe osteochondritis dissecans of the knee: incidence in two families.</strong>
|
|
Skeletal Radiol. 17: 407-412, 1988.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3238439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3238439</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3238439" 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/BF00361659" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Warman1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Warman, M. L., McCarthy, M. T., Perala, M., Vuorio, E., Knoll, J. H. M., McDaniels, C. N., Mayne, R., Beier, D. R., Olsen, B. R.
|
|
<strong>The genes encoding alpha-2(IX) collagen (COL9A2) map to human chromosome 1p32.3-p33 and mouse chromosome 4.</strong>
|
|
Genomics 23: 158-162, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7829066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7829066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7829066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1994.1472" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 07/13/2017
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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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Ingrid M. Wentzensen - updated : 12/5/2014<br>Marla J. F. O'Neill - updated : 10/7/2011<br>Cassandra L. Kniffin - updated : 10/12/2005<br>Deborah L. Stone - updated : 11/11/2003<br>Harry C. Dietz - updated : 7/16/1999<br>Victor A. McKusick - updated : 6/28/1999
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
|
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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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Victor A. McKusick : 6/26/1987
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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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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alopez : 06/20/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 12/06/2017<br>mgross : 07/13/2017<br>carol : 11/17/2016<br>carol : 01/05/2015<br>carol : 12/5/2014<br>alopez : 10/7/2011<br>terry : 10/7/2011<br>terry : 11/24/2010<br>wwang : 11/15/2010<br>ckniffin : 11/9/2010<br>wwang : 10/26/2005<br>wwang : 10/24/2005<br>ckniffin : 10/12/2005<br>tkritzer : 11/14/2003<br>tkritzer : 11/11/2003<br>tkritzer : 11/3/2003<br>carol : 6/17/2003<br>terry : 4/16/2002<br>alopez : 11/23/1999<br>carol : 11/4/1999<br>alopez : 7/16/1999<br>terry : 7/16/1999<br>carol : 7/9/1999<br>jlewis : 7/7/1999<br>terry : 6/28/1999<br>dkim : 12/9/1998<br>terry : 5/29/1998<br>mark : 1/8/1996<br>terry : 1/4/1996<br>terry : 3/7/1995<br>carol : 1/11/1995<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>ddp : 10/26/1989<br>marie : 3/25/1988
|
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
|
<strong>*</strong> 120260
|
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</span>
|
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</h3>
|
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</div>
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<div>
|
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<h3>
|
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<span class="mim-font">
|
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|
|
COLLAGEN, TYPE IX, ALPHA-2; COL9A2
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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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<div>
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<p>
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: COL9A2</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 1p34.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 1:40,300,489-40,317,286 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
|
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<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">
|
|
1p34.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Stickler syndrome, type V
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614284
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
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</tr>
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|
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|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Epiphyseal dysplasia, multiple, 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
600204
|
|
</span>
|
|
</td>
|
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<td>
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<span class="mim-font">
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Autosomal dominant
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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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</tr>
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</tbody>
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</table>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The COL9A2 gene encodes the alpha-2 subunit of collagen type IX. Type IX collagen, a heterotrimer of alpha-1 (COL9A1; 120210), alpha-2, and alpha-3 (COL9A3; 120270) chains specific for this type of collagen, is a cartilage-specific fibril-associated collagen (Perala et al., 1993). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In the process of characterizing genomic clones for the mouse COL9A2 gene, Perala et al. (1993) also used 4 pairs of oligonucleotide primers designed for amplification of murine exon sequences to construct cDNA clones for the human gene spanning more than 90% of the coding region. The amino acid and nucleotide sequence identities between human and chick are 78 and 71%, respectively. </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>Perala et al. (1993) assigned the human COL9A2 gene to chromosome 1 by study of a panel of DNAs from human/rodent somatic cell hybrids. </p><p>Warman et al. (1994) used fluorescence in situ hybridization to regionalize the COL9A2 gene to 1p33-p32.3. A single-strand conformation polymorphism within the murine gene was used to map Col9a2 to mouse chromosome 4. Since one form of multiple epiphyseal dysplasia (EDM2; 600204) maps to the same region of chromosome 1, COL9A2 was considered to be a candidate gene for that disorder. </p><p>Hellsten et al. (1995) demonstrated that the COL9A2 gene is in a 1-Mb contig, proximal to RLF (180610) and MYCL1 (164850). </p><p>Gross (2017) mapped the COL9A2 gene to chromosome 1p34.2 based on an alignment of the COL9A2 sequence (GenBank AF019406) with the genomic sequence (GRCh38).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>The cartilage collagen fibrils are formed from fibrillar collagens II and XI (120280), while collagen IX is located on the fibril surface (see Figure 2 in Muragaki et al., 1996). The alpha-1(IX) chain contains a large N-terminal globular domain (NC4); a chondroitin sulfate chain is attached to the alpha-2(IX) chain (Muragaki et al., 1996). </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>Multiple Epiphyseal Dysplasia 2</em></strong></p><p>
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The usefulness of the candidate gene approach for identification of a basic gene defect was illustrated by the finding of a mutation in the COL9A2 gene (120260.0001) in a Dutch kindred with multiple epiphyseal dysplasia-2 (EDM2; 600204) showing linkage to DNA markers in the region of 1p32 (Muragaki et al., 1996). Muragaki et al. (1996) stated that the results provided by the EDM2 'experiment of nature' represent the first in vivo evidence for the role of collagen IX in human articular cartilage. </p><p>Holden et al. (1999) described 2 families with distinctive oligoepiphyseal forms of multiple epiphyseal dysplasia, in which heterozygosity for different mutations in the COL9A2 gene (120260.0002 and 120260.0003) was found. Both of these mutations resulted in the skipping of exon 3 from the COL9A2 mRNA, but the position of the mutation in the splice donor site determined the stability of the mRNA produced from the mutant allele. </p><p><strong><em>Stickler Syndrome V</em></strong></p><p>
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In a large 5-generation consanguineous pedigree of Asian Indian origin segregating autosomal recessive Stickler syndrome (STL5; 614284), Baker et al. (2011) analyzed 3 candidate collagen IX-related genes and identified homozygosity for an 8-bp deletion in the COL9A2 gene (120260.0006) that segregated with disease in the family. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between intervertebral disc disease (IDD; 603932) and variation in the COL9A2 gene, see 120260.0004.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a canine model of oculoskeletal dysplasia in Samoyed dogs, termed drd2 (dwarfism with retinal dysplasia type 2), Goldstein et al. (2010) identified a homozygous 1,267-bp deletion in the 5-prime end of the COL9A2 gene that segregated with the phenotype. The mutation affected the COL3 domain of the gene. Northern blot analysis showed reduced RNA expression of the COL9A2 gene in affected retinas. The drd2 phenotype is characterized by short-limb dwarfism and severe ocular defects, such as vitreous dysplasia, retinal detachment, and cataracts. Heterozygous carrier dogs may exhibit a milder ocular phenotype, such as vitreal strands or retinal dysplasia, but have a normal appendicular skeleton. Goldstein et al. (2010) noted that the drd2 phenotype resembles human hereditary arthroophthalmopathies such as Stickler syndrome, Kniest dysplasia (156550), and Marshall syndrome (154780). </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 EPIPHYSEAL DYSPLASIA, MULTIPLE, 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL9A2, IVS3DS, T-C, +2
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<br />
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SNP: rs1569763139,
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ClinVar: RCV000018680
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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>Muragaki et al. (1996) demonstrated a mutation in affected members of a family with multiple epiphyseal dysplasia (EDM2; 600204) that showed linkage to the 1p32 region. Affected members were heterozygous for a splice site mutation causing exon skipping during RNA splicing and an in-frame loss of 12 amino acids within the alpha-2 (IX) collagen chain. The results provided the first in vivo evidence for the role of collagen IX in human articular cartilage. The clinical findings in the family were entirely characteristic of MED although hip complaints were less conspicuous than in many kindreds. The specific mutation was a T-to-C transition in the consensus donor splice site of intron 3, resulting in the skipping of exon 3. </p><p>Jackson et al. (2010) reported a large 4-generation family with autosomal dominant transmission of EDM2 associated with the T-to-C transition in intron 3 (186+2T-C) of the COL9A2 gene. The family had previously been reported by Versteylen et al. (1988). The proband was a 33-year-old woman with short stature who complained of stiff and painful hands and knees since age 4 years. Radiographs of the knees showed Blount disease (progressive varus deformity of the proximal tibia associated with internal torsion of the tibia) and of the spine showed mild spondyloarthrotic abnormalities in the thoracic region. Her sister had painful and swollen knees since age 4 years and developed severe osteochondritis dissecans as an adult. Two sons of the proband were also affected, showing pain in the knees during walking and clumsy walking. These boys also had frontal bossing, depressed nasal bridge, and were easily fatigued with mild muscle weakness. Radiographs of 1 son at age 3 years showed delayed ossification of the epiphyses, small proximal femoral epiphyses, and small femoral and tibial epiphyses around the knees. Skeletal muscle biopsy and mitochondrial studies showed no significant abnormalities, only mild variations in fiber size and slightly diminished ATP production. Jackson et al. (2010) commented on the mild myopathy present in the boys, and noted that EDM is characterized by clinical variability even within the same family. The mild myopathic and mitochondrial changes observed may be secondary to a tendinopathy and/or cell stress response resulting from expression of mutant collagen. </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 EPIPHYSEAL DYSPLASIA, MULTIPLE, 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL9A2, IVS3DS, 186G-A
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<br />
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SNP: rs1085307973,
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gnomAD: rs1085307973,
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ClinVar: RCV000489270, RCV001807641, RCV004740263
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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 family K of Holden et al. (1999) with multiple epiphyseal dysplasia-2 (EDM2; 600204), the proband was a 17-year-old male of normal height who was diagnosed in childhood with pain in the joints, mostly the knees, and genu varum. Radiographs showed major epiphyseal changes in the knees and hands, and almost no changes in the hips. The spine also appeared normal. The molecular change was a G-to-A transition in the last nucleotide of exon 3, changing the last codon of exon 3 from CCG (pro) to CCA (also pro). Although there was no change in the amino acid, the change interfered with splicing. </p><p>Nakashima et al. (2005) identified the exon 3 G-to-A transition in the COL9A2 gene in affected members of a Japanese family with EDM2. The proband had bilateral double-layered patellae, indicating that this unusual feature is not unique to autosomal recessive multiple epiphyseal dysplasia with homozygous mutations in the DTDST gene (606718; see EDM4 226900). </p><p>Jackson et al. (2010) reported a patient with EDM2 characterized by onset at age 3 years of an abnormal gait associated with proximal muscle weakness. He had left-sided developmental dysplasia of the hip. The family history was positive for hypodontia and for osteochondritis dissecans. However, 2 affected adult family members showed improvement of the disorder after puberty. The proband was heterozygous for the 186G-A transition in the splice donor sequence of exon 3 of the COL9A2 gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 EPIPHYSEAL DYSPLASIA, MULTIPLE, 2</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL9A2, IVS3DS, G-C, +5
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<br />
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SNP: rs1569763108,
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ClinVar: RCV000018682, RCV005089274
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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>Family G reported by Holden et al. (1999) with an oligoepiphyseal form of multiple epiphyseal dysplasia (EDM2; 600204) and a mutation in the COL9A2 gene had affected members in 4 generations, of whom a mother and her 2 sons were available for study. They were slightly short in stature (adult height, 158 cm), and all 3 developed genu valgum, which required surgical correction. The mother started walking late and with a stiff gait that became more noticeable during ages 5 to 7 years. Her legs became increasingly bowed, and at age 17 she underwent tibial osteotomy. She had developed increasing problems with pain in her hands, lumbar spine, and ankles. Her 2 sons walked at age 2 years with a stiff gait. Epiphyseal dysplasia was recognized in them in early childhood, and they underwent tibial osteotomy for genu valgum at ages 14 and 13, respectively. They continued to have mild joint symptoms, including intermittent lumbar back pain and knee pain with swelling. Changes were not found clinically or radiographically in the hips. Affected members showed heterozygosity for a G-to-C transversion at position +5 of intron 3. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0004 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</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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COL9A2, GLN326TRP
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<br />
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SNP: rs137853213,
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ClinVar: RCV000018683, RCV000710925
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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>This variant, formerly titled INTERVERTEBRAL DISC DISEASE, SUSCEPTIBILITY TO, has been reclassified because its contribution to the disorder has not been confirmed.</p><p>In a study that examined for allelic variation in the COL9A2 gene in Finnish individuals with sciatica and radiologically documented intervertebral disc disease (IDD; 603932), Annunen et al. (1999) found a substitution of tryptophan for glutamine at codon 326. This change was found in 6 of 157 individuals with disc disease but in none of 174 controls. Further analysis of the families of 4 of the original patients revealed that all individuals heterozygous for the trp substitution demonstrated the disease phenotype. Many individuals within these families had IDD but not the trp allele. The authors invoked a high phenocopy rate to reconcile this observation with the conclusion that this sequence variant within COL9A2 contributes to the pathogenesis of disease. In the disease model chosen, this locus accounted for 10% of disease prevalence. Under these constraints, Annunen et al. (1999) demonstrated a lod score of 4.5 at a recombination fraction of 0.12. Subsequent linkage disequilibrium analysis conditional on linkage gave an additional lod score of 7.1. The authors did not exclude the possibility that a true disease locus may lie in close physical proximity to COL9A2. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0005 EPIPHYSEAL DYSPLASIA, MULTIPLE, 2</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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COL9A2, IVS3DS, G-C, -1
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<br />
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SNP: rs1085307973,
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gnomAD: rs1085307973,
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ClinVar: RCV000018684, RCV001851921
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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 12 affected members from a 4-generation family with a relatively hip-sparing multiple epiphyseal dysplasia phenotype (EDM2; 600204), Fiedler et al. (2002) identified a G-to-C mutation in the last nucleotide of exon 3 of the COL9A2 gene. The disorder was characterized by childhood onset of pain and stiffness in the knees. Finger joints, ankles, and elbows became symptomatic during early adult life. Some adult patients had free articular bodies which resulted in locking of the joints. Fiedler et al. (2002) noted that a G-to-A change at the same nucleotide had earlier been found to cause EDM2 (120260.0002). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0006 STICKLER SYNDROME V (1 family)</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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COL9A2, 8-BP DEL, NT843
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<br />
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SNP: rs606231376,
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ClinVar: RCV000022493
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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 an affected sister and brother from a large 5-generation consanguineous pedigree of Asian Indian origin segregating autosomal recessive Stickler syndrome (STL5; 614284), Baker et al. (2011) identified homozygosity for an 8-bp deletion in the COL9A2 gene involving the last 4 nucleotides of exon 16 and the first 4 nucleotides of IVS16 (843_846+4del8). The deletion was predicted to cause a frameshift and downstream premature termination codon (Asp281GlnfsTer70). The mutation was detected in heterozygosity in the sibs' unaffected brother and parents. </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>REFERENCES</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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<ol>
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<li>
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<p class="mim-text-font">
|
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Annunen, S., Paassilta, P. Lohiniva, J., Perala, M., Pihlajamaa, T., Karppinen, J., Tervonen, O., Kroger, H., Lahde, S., Vanharanta, H., Ryhanen, L., Goring, H. H. H., Ott, J., Prockop, D. J., Ala-Kokko, L.
|
|
<strong>An allele of COL9A2 associated with intervertebral disc disease.</strong>
|
|
Science 285: 409-412, 1999.
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[PubMed: 10411504]
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[Full Text: https://doi.org/10.1126/science.285.5426.409]
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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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Baker, S., Booth, C., Fillman, C., Shapiro, M., Blair, M. P., Hyland, J. C., Ala-Kokko, L.
|
|
<strong>A loss of function mutation in the COL9A2 gene cause autosomal recessive Stickler syndrome.</strong>
|
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Am. J. Med. Genet. 155A: 1668-1672, 2011.
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[PubMed: 21671392]
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Holden, P., Canty, E. G., Mortier, G. R., Zabel, B., Spranger, J., Carr, A., Grant, M. E., Loughlin, J. A., Briggs, M. D.
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<strong>Identification of novel pro-alpha-2(IX) collagen gene mutations in two families with distinctive oligo-epiphyseal forms of multiple epiphyseal dysplasia.</strong>
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Jackson, G. C., Marcus-Soekarman, D., Stolte-Dijkstra, I., Verrips, A., Taylor, J. A., Briggs, M. D.
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<strong>Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.</strong>
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Muragaki, Y., Mariman, E. C. M., van Beersum, S. E. C., Perala, M., van Mourik, J. B. A., Warman, M. L., Olsen, B. R., Hamel, B. C. J.
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<strong>A mutation in the gene encoding the alpha-2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2).</strong>
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<strong>Double-layered patella in multiple epiphyseal dysplasia is not exclusive to DTDST mutation. (Letter)</strong>
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Perala, M., Hanninen, M., Hastbacka, J., Elima, K., Vuorio, E.
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Versteylen, R. J., Zwemmer, A., Lorie, C. A. M., Schuur, K. H.
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<strong>Multiple epiphyseal dysplasia complicated by severe osteochondritis dissecans of the knee: incidence in two families.</strong>
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Warman, M. L., McCarthy, M. T., Perala, M., Vuorio, E., Knoll, J. H. M., McDaniels, C. N., Mayne, R., Beier, D. R., Olsen, B. R.
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<strong>The genes encoding alpha-2(IX) collagen (COL9A2) map to human chromosome 1p32.3-p33 and mouse chromosome 4.</strong>
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Genomics 23: 158-162, 1994.
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[PubMed: 7829066]
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[Full Text: https://doi.org/10.1006/geno.1994.1472]
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