5612 lines
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- *600310 - CARTILAGE OLIGOMERIC MATRIX PROTEIN; COMP
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*600310</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#evolution">Evolution</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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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/600310">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div id="mimFloatingLinksMenu">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div 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 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="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=ENSG00000105664;t=ENST00000222271" 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=1311" 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=600310" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<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=ENSG00000105664;t=ENST00000222271" 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_000095" 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_000095" 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=600310" 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=02632&isoform_id=02632_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/COMP" 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/602450,1184517,1184519,2623750,3978233,22759999,27530066,40217843,62897993,84570077,115527966,119605141,119605142,119605143,158254622,194383694,194387546,194387576,209572601,444737797" 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/P49747" 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=1311" 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=ENSG00000105664;t=ENST00000222271" 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=COMP" 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=COMP" 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+1311" 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/COMP" 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:1311" 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/1311" 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=chr19&hgg_gene=ENST00000222271.7&hgg_start=18782773&hgg_end=18791305&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 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/genes/HGNC:2227" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/comp" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=600310[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=600310[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/COMP/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/ENSG00000105664" 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=COMP" 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=COMP" 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=COMP" 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=COMP&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/PA26744" 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:2227" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0031850.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:88469" 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/COMP#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:88469" 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/1311/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=1311" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060606-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
|
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<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:1311" 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=COMP&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
|
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 22567005, 715673002<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
600310
|
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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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|
CARTILAGE OLIGOMERIC MATRIX PROTEIN; COMP
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</span>
|
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</h3>
|
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</div>
|
|
<div>
|
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<br />
|
|
</div>
|
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<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
THROMBOSPONDIN V; THBS5
|
|
</span>
|
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</h4>
|
|
</div>
|
|
</div>
|
|
<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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=COMP" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">COMP</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/19/473?start=-3&limit=10&highlight=473">19p13.11</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:18782773-18791305&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'})">19:18,782,773-18,791,305</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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</span>
|
|
</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=619161,132400,177170" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/473?start=-3&limit=10&highlight=473">
|
|
19p13.11
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Carpal tunnel syndrome 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/619161"> 619161 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
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|
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|
|
|
|
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|
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</tr>
|
|
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|
|
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|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Epiphyseal dysplasia, multiple, 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/132400"> 132400 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Pseudoachondroplasia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/177170"> 177170 </a>
|
|
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<p>COMP is a pentameric extracellular matrix protein that catalyzes the assembly of collagens and promotes formation of well-defined fibrils (<a href="#10" class="mim-tip-reference" title="Halasz, K., Kassner, A., Morgelin, M., Heinegard, D. <strong>COMP acts as a catalyst in collagen fibrillogenesis.</strong> J. Biol. Chem. 282: 31166-31173, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17716974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17716974</a>] [<a href="https://doi.org/10.1074/jbc.M705735200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17716974">Halasz et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17716974" 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>Cartilage oligomeric matrix protein is a 524-kD protein that is expressed at high levels in the territorial matrix of chondrocytes. The sequences of rat and bovine COMP indicate that it is a member of the thrombospondin gene family (<a href="#26" class="mim-tip-reference" title="Newton, G., Weremowicz, S., Morton, C. C., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Lawler, J. <strong>Characterization of human and mouse cartilage oligomeric matrix protein.</strong> Genomics 24: 435-439, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7713493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7713493</a>] [<a href="https://doi.org/10.1006/geno.1994.1649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7713493">Newton et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7713493" 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="#25" class="mim-tip-reference" title="Maddox, B. K., Mokashi, A., Keene, D. R., Bachinger, H. P. <strong>A cartilage oligomeric matrix protein mutation associated with pseudoachondroplasia changes the structural and functional properties of the type 3 domain.</strong> J. Biol. Chem. 275: 11412-11417, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10753957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10753957</a>] [<a href="https://doi.org/10.1074/jbc.275.15.11412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10753957">Maddox et al. (2000)</a> reported that 5 identical COMP molecules associate via their N-terminal coiled-coil domains into a bouquet-like structure with 5 flexible arms. The flexible arms contain 4 EGF-like repeats, followed by 8 thrombospondin (see <a href="/entry/188060">188060</a>) type 3 repeats, and a large C-terminal globular domain. The type 3 repeats are predicted to bind calcium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10753957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Kleerekoper, Q., Hecht, J. T., Putkey, J. A. <strong>Disease-causing mutations in cartilage oligomeric matrix protein cause an unstructured Ca(2+) binding domain.</strong> J. Biol. Chem. 277: 10581-10589, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11782471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11782471</a>] [<a href="https://doi.org/10.1074/jbc.M109944200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11782471">Kleerekoper et al. (2002)</a> stated that full-length human COMP contains 757 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11782471" 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="Halasz, K., Kassner, A., Morgelin, M., Heinegard, D. <strong>COMP acts as a catalyst in collagen fibrillogenesis.</strong> J. Biol. Chem. 282: 31166-31173, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17716974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17716974</a>] [<a href="https://doi.org/10.1074/jbc.M705735200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17716974">Halasz et al. (2007)</a> stated that in young cartilage COMP is primarily identified close to chondrocytes, whereas in adult cartilage it is found in the interterritorial region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17716974" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunohistochemical analysis, <a href="#1" class="mim-tip-reference" title="Agarwal, P., Zwolanek, D., Keene, D. R., Schulz, J.-N., Blumbach, K., Heinegard, D., Zaucke, F., Paulsson, M., Krieg, T., Koch, M., Eckes, B. <strong>Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure.</strong> J. Biol. Chem. 287: 22549-22559, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22573329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22573329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22573329[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/10.1074/jbc.M111.335935" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22573329">Agarwal et al. (2012)</a> detected COMP expression in normal human skin. COMP localized in a continuous linear pattern mainly at the superficial papillary dermis, just below epidermal keratinocytes. Much lower expression was detected in reticular dermis. Quantitative real-time RT-PCR detected abundant COMP expression in extracts of separated dermis and in cultured primary dermal fibroblasts, but not in epidermal extracts or cultured HaCaT keratinocytes. Electron microscopy revealed that COMP localized subepidermally in clusters that overlapped with, but were not limited to, anchoring plaques. In skin, COMP expression partly colocalized with collagens XII (COL12A1; <a href="/entry/120320">120320</a>) and XIV (COL14A1; <a href="/entry/120324">120324</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22573329" 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="#32" class="mim-tip-reference" title="Thur, J., Rosenberg, K., Nitsche, D. P., Pihlajamaa, T., Ala-Kokko, L., Heinegard, D., Paulsson, M., Maurer, P. <strong>Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of calcium and collagen I, II, and IX.</strong> J. Biol. Chem. 276: 6083-6092, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11084047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11084047</a>] [<a href="https://doi.org/10.1074/jbc.M009512200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11084047">Thur et al. (2001)</a> expressed recombinant wildtype rat COMP that showed structural and functional properties identical to COMP isolated from cartilage. The fragment encompassing the 8 type-3 repeats bound 14 calcium ions with moderate affinity and high cooperativity and presumably formed 1 large disulfide-bonded folding unit. A recombinant PSACH mutant COMP in which asp469 was deleted and a EDM mutant COMP in which asp361 was substituted by tyr (D361Y) were both secreted into the cell culture medium of human cells. The number of bound calcium ions was reduced. In addition to collagen I (see <a href="/entry/120150">120150</a>) and II (see <a href="/entry/120140">120140</a>), collagen IX normally binds to COMP with high affinity; the PSACH and EDM mutations reduced the binding of these 3 collagens and resulted in altered zinc dependence. These interactions may explain why EDM can also be caused by mutations in collagen IX genes (COL9A2, <a href="/entry/120260">120260</a> and COL9A3, <a href="/entry/120270">120270</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11084047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using rotary shadowing electron microscopy and immobilized proteins, <a href="#13" class="mim-tip-reference" title="Holden, P., Meadows, R. S., Chapman, K. L., Grant, M. E., Kadler, K. E., Briggs, M. D. <strong>Cartilage oligomeric matrix protein interacts with type IX collagen, and disruptions to these interactions identify a pathogenetic mechanism in a bone dysplasia family.</strong> J. Biol. Chem. 276: 6046-6055, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11087755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11087755</a>] [<a href="https://doi.org/10.1074/jbc.M009507200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11087755">Holden et al. (2001)</a> characterized the interaction between purified chick sternal cartilage type IX collagen (see COL9A1, <a href="/entry/120210">120210</a>) and purified fetal bovine Comp or the isolated human COMP C-terminal domain. They identified a collagen-binding site between residues 579 and 595 of the C-terminal domain of COMP that bound each of 4 noncollagenous domains in collagen IX. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11087755" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a yeast 2-hybrid screen, <a href="#20" class="mim-tip-reference" title="Liu, C., Kong, W., Ilalov, K., Yu, S., Xu, K., Prazak, L., Fajardo, M., Sehgal, B., Di Cesare, P. E. <strong>ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein.</strong> FASEB J. 20: 988-990, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16585064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16585064</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16585064[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/10.1096/fj.05-3877fje" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16585064">Liu et al. (2006)</a> found that human COMP interacted with the extracellular metalloprotease Adamts7 (<a href="/entry/605009">605009</a>) in a rat brain cDNA library. The interaction was confirmed by protein pull-down and immunoprecipitation experiments. Domain analysis revealed that the C-terminal thrombospondin repeats of Adamts7 interacted with the EGF-like domain of COMP. Both full-length Adamts7 and the isolated catalytic domain (amino acids 217 to 468) of human ADAMTS7 digested COMP in a dose- and time-dependent manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16585064" 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="Halasz, K., Kassner, A., Morgelin, M., Heinegard, D. <strong>COMP acts as a catalyst in collagen fibrillogenesis.</strong> J. Biol. Chem. 282: 31166-31173, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17716974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17716974</a>] [<a href="https://doi.org/10.1074/jbc.M705735200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17716974">Halasz et al. (2007)</a> stated that pentameric bovine Comp binds via each C-terminal globule domain to 1 of 4 sites on collagens I (see <a href="/entry/120150">120150</a>) and II (see <a href="/entry/120140">120140</a>). They found that monomeric recombinant bovine Comp lacking the N-terminal coiled-coil domain showed weak fibril formation with collagens I and II. Fibril formation was much faster in the presence of purified pentameric Comp. Comp interacted primarily with free collagen I and II molecules, bringing several molecules to close proximity and promoting their assembly. Comp was not associated with mature fibrils and dissociates from the collagen molecules or their early assemblies. <a href="#10" class="mim-tip-reference" title="Halasz, K., Kassner, A., Morgelin, M., Heinegard, D. <strong>COMP acts as a catalyst in collagen fibrillogenesis.</strong> J. Biol. Chem. 282: 31166-31173, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17716974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17716974</a>] [<a href="https://doi.org/10.1074/jbc.M705735200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17716974">Halasz et al. (2007)</a> concluded that COMP catalyzes fibril formation by promoting early association of collagen molecules, leading to increased rate of fibrillogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17716974" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By characterizing mouse constructs expressed in human HEK293-EBNA cells, <a href="#1" class="mim-tip-reference" title="Agarwal, P., Zwolanek, D., Keene, D. R., Schulz, J.-N., Blumbach, K., Heinegard, D., Zaucke, F., Paulsson, M., Krieg, T., Koch, M., Eckes, B. <strong>Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure.</strong> J. Biol. Chem. 287: 22549-22559, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22573329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22573329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22573329[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/10.1074/jbc.M111.335935" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22573329">Agarwal et al. (2012)</a> found that pentameric Comp bound collagens XII and XIV. In both cases, Comp bound to C-terminal collagenous domains of the collagens, but not to their large noncollagenous-3 domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22573329" 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="#4" class="mim-tip-reference" title="Briggs, M. D., Hoffman, S. M. G., King, L. M., Olsen, A. S., Mohrenweiser, H., Leroy, J. G., Mortier, G. R., Rimoin, D. L., Lachman, R. S., Gaines, E. S., Cekleniak, J. A., Knowlton, R. G., Cohn, D. H. <strong>Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.</strong> Nature Genet. 10: 330-336, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670472</a>] [<a href="https://doi.org/10.1038/ng0795-330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670472">Briggs et al. (1995)</a> demonstrated that the COMP gene contains 19 exons. Exons 4-19, which encode the EGF-like (type II) repeats, calmodulin-like (type III) repeats (CLRs), and the C-terminal domain, correspond in sequence and intron location to the thrombospondin genes, whereas exons 1-3 are unique to COMP. They presented a table giving the gene structure of COMP in terms of exon size, intron location, and nucleotide sequence of the splice donor and splice acceptor regions of all exon/intron junctions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By Southern blot analysis of a somatic cell hybrid DNA panel and by isotopic in situ hybridization, <a href="#26" class="mim-tip-reference" title="Newton, G., Weremowicz, S., Morton, C. C., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Lawler, J. <strong>Characterization of human and mouse cartilage oligomeric matrix protein.</strong> Genomics 24: 435-439, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7713493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7713493</a>] [<a href="https://doi.org/10.1006/geno.1994.1649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7713493">Newton et al. (1994)</a> mapped the human COMP gene to 19p13.1. <a href="#26" class="mim-tip-reference" title="Newton, G., Weremowicz, S., Morton, C. C., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Lawler, J. <strong>Characterization of human and mouse cartilage oligomeric matrix protein.</strong> Genomics 24: 435-439, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7713493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7713493</a>] [<a href="https://doi.org/10.1006/geno.1994.1649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7713493">Newton et al. (1994)</a> mapped the murine Comp gene to the central region of mouse chromosome 8 by use of an interspecific backcross mapping panel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7713493" 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="#26" class="mim-tip-reference" title="Newton, G., Weremowicz, S., Morton, C. C., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Lawler, J. <strong>Characterization of human and mouse cartilage oligomeric matrix protein.</strong> Genomics 24: 435-439, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7713493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7713493</a>] [<a href="https://doi.org/10.1006/geno.1994.1649" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7713493">Newton et al. (1994)</a> reported a phylogenetic analysis indicating that the COMP gene and a precursor of the thrombospondin-3 (<a href="/entry/188062">188062</a>) and thrombospondin-4 (<a href="/entry/600715">600715</a>) genes were produced by a gene duplication that occurred 750 million years ago. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7713493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Pseudoachondroplasia and Multiple Epiphyseal Dysplasia-1</em></strong></p><p>
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COMP was a candidate gene for the site of the mutation in both pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>) and one form of multiple epiphyseal dysplasia (EDM1; <a href="/entry/132400">132400</a>) because both disorders mapped to 19p13.1-p12. <a href="#12" class="mim-tip-reference" title="Hecht, J. T., Nelson, L. D., Crowder, E., Wang, Y., Elder, F. F. B., Harrison, W. R., Francomano, C. A., Prange, C. K., Lennon, G. G., Deere, M., Lawler, J. <strong>Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.</strong> Nature Genet. 10: 325-329, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670471</a>] [<a href="https://doi.org/10.1038/ng0795-325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670471">Hecht et al. (1995)</a> used single-strand conformation polymorphism (SSCP) analysis and nucleotide sequencing to identify COMP mutations in 8 familial and isolated PSACH cases. All mutations involved either a 1-bp change or a 3-bp deletion in the same exon. In 6 patients, 6 mutation events either deleted or changed well-conserved aspartic acid residues within the calcium-binding type-3 repeats (see <a href="#0001">600310.0001</a> and <a href="#0004">600310.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the process of determining the COMP genomic sequence, <a href="#4" class="mim-tip-reference" title="Briggs, M. D., Hoffman, S. M. G., King, L. M., Olsen, A. S., Mohrenweiser, H., Leroy, J. G., Mortier, G. R., Rimoin, D. L., Lachman, R. S., Gaines, E. S., Cekleniak, J. A., Knowlton, R. G., Cohn, D. H. <strong>Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.</strong> Nature Genet. 10: 330-336, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670472</a>] [<a href="https://doi.org/10.1038/ng0795-330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670472">Briggs et al. (1995)</a> identified a polymorphic (GAAA)12 repeat at the 3-prime end of an Alu element within intron 9. Using this marker for study of linkage in 2 large families previously used to establish linkage to chromosome 19 of PSACH/EDM1, they found 2 individuals, 1 from each family, who were not recombinant at the COMP marker. The 2 had been shown previously to be recombinant at flanking markers used to define the 800-kb PSACH/EDM1 interval. <a href="#4" class="mim-tip-reference" title="Briggs, M. D., Hoffman, S. M. G., King, L. M., Olsen, A. S., Mohrenweiser, H., Leroy, J. G., Mortier, G. R., Rimoin, D. L., Lachman, R. S., Gaines, E. S., Cekleniak, J. A., Knowlton, R. G., Cohn, D. H. <strong>Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.</strong> Nature Genet. 10: 330-336, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670472</a>] [<a href="https://doi.org/10.1038/ng0795-330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670472">Briggs et al. (1995)</a> also demonstrated specific mutations in the COMP gene in 2 patients with pseudoachondroplasia (<a href="#0006">600310.0006</a> and <a href="#0018">600310.0018</a>) and 1 patient with the Fairbank form of EDM (<a href="#0005">600310.0005</a>). Thus, the allelic nature of these 2 disorders was established. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670472" 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="#30" class="mim-tip-reference" title="Susic, S., McGrory, J., Ahier, J., Cole, W. G. <strong>Multiple epiphyseal dysplasia and pseudoachondroplasia due to novel mutations in the calmodulin-like repeats of cartilage oligomeric matrix protein.</strong> Clin. Genet. 51: 219-224, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9184241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9184241</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1997.tb02458.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9184241">Susic et al. (1997)</a> found heterozygosity for a 12-bp deletion in exon 10 of the COMP gene in a child with a mild form of pseudoachondroplasia. A child with the Fairbank type of multiple epiphyseal dysplasia was heterozygous for a cys371-to-ser amino acid substitution in the fourth CLR. These findings were thought to support the proposal that deletions and insertions within the calmodulin-like domain produce pseudoachondroplasia, whereas amino acid substitutions within this domain may produce either pseudoachondroplasia or EDM. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9184241" 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="Briggs, M. D., Mortier, G. R., Cole, W. G., King, L. M., Golik, S. S., Bonaventure, J., Nuytinck, L., De Paepe, A., Leroy, J. G., Biesecker, L., Lipson, M., Wilcox, W. R., Lachman, R. S., Rimoin, D. L., Knowlton, R. G., Cohn, D. H. <strong>Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.</strong> Am. J. Hum. Genet. 62: 311-319, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463320</a>] [<a href="https://doi.org/10.1086/301713" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9463320">Briggs et al. (1998)</a> reported identification of COMP mutations in an additional 14 families with PSACH or EDM phenotypes. Mutations predicted to result in single amino acid deletions or substitutions, all in the region of the COMP gene encoding the CLR elements, were identified in patients with moderate to severe PSACH (see, e.g., <a href="#0004">600310.0004</a> and <a href="#0018">600310.0018</a>). They also identified within this domain a missense mutation that produced EDM of the Fairbank type. In 2 families, one with mild PSACH and the other with a form of EDM, they identified different substitutions for a residue in the C-terminal globular region of COMP. Both the clinical presentations of these 2 families and the identification of mutations in the COMP gene provided evidence of phenotypic overlap between PSACH and EDM. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 12 patients with PSACH, <a href="#6" class="mim-tip-reference" title="Deere, M., Sanford, T., Ferguson, H. L., Daniels, K., Hecht, J. T. <strong>Identification of twelve mutations in cartilage oligomeric matrix protein (COMP) in patients with pseudoachondroplasia.</strong> Am. J. Med. Genet. 80: 510-513, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9880218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9880218</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19981228)80:5<510::aid-ajmg14>3.0.co;2-f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9880218">Deere et al. (1998)</a> identified 12 mutations in the COMP gene, including 10 novel mutations. The site of the mutations emphasized the importance of the calcium-binding domains and the globular domain to the function of COMP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9880218" 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="Deere, M., Sanford, T., Francomano, C. A., Daniels, K., Hecht, J. T. <strong>Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Am. J. Med. Genet. 85: 486-490, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10405447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10405447</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19990827)85:5<486::aid-ajmg10>3.0.co;2-o" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10405447">Deere et al. (1999)</a> reported 9 novel mutations in COMP causing PSACH and EDM1. These included 4 mutations in exons 13C and 14 where no previous mutations had been identified, a case of PSACH resulting from an expansion of the 5 aspartates in exon 17B, and a PSACH family with somatic/germline mosaicism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10405447" 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="#15" class="mim-tip-reference" title="Ikegawa, S., Ohashi, H., Nishimura, G., Kim, K. C., Sannohe, A., Kimizuka, M., Fukushima, Y., Nagai, T., Nakamura, Y. <strong>Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Hum. Genet. 103: 633-638, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921895</a>] [<a href="https://doi.org/10.1007/s004390050883" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921895">Ikegawa et al. (1998)</a> screened the COMP gene in 15 patients with PSACH or EDM by direct sequencing of PCR products from genomic DNA. They identified 10 mutations involving conserved residues among the 8 CLRs of the gene product: 7 were missense mutations in exons 9, 10, 11, 13 or 14, and the other 3 resulted from deletion of 1 of the 5 GAC repeats in exon 13 (<a href="#0004">600310.0004</a>). They found that the GAC repeats in the seventh CLR in exon 13 represent a hotspot for mutation and that mutations in the seventh calmodulin-like repeat produce severe PSACH phenotypes whereas mutations elsewhere in the gene exhibit mild PSACH or EDM phenotypes. They suggested that these genotype/phenotype correlations may facilitate molecular diagnosis and classification of PSACH and EDM, and provide insight into the relationship between structure and function of the COMP gene product. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921895" 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="Delot, E., King, L. M., Briggs, M. D., Wilcox, W. R., Cohn, D. H. <strong>Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene.</strong> Hum. Molec. Genet. 8: 123-128, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887340</a>] [<a href="https://doi.org/10.1093/hmg/8.1.123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887340">Delot et al. (1999)</a> stated that about one-third of patients with PSACH are heterozygous for deletion of 1 codon within a very short triplet repeat, (GAC)5, which encodes 5 consecutive aspartic acid residues within the calmodulin-like region of the COMP protein (<a href="#0004">600310.0004</a>). <a href="#8" class="mim-tip-reference" title="Delot, E., King, L. M., Briggs, M. D., Wilcox, W. R., Cohn, D. H. <strong>Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene.</strong> Hum. Molec. Genet. 8: 123-128, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887340</a>] [<a href="https://doi.org/10.1093/hmg/8.1.123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887340">Delot et al. (1999)</a> identified 2 expansion mutations in this repeat: an EDM patient carrying a (GAC)6 allele (<a href="#0012">600310.0012</a>), and a PSACH patient carrying a (GAC)7 allele (<a href="#0011">600310.0011</a>). These were among the shortest disease-causing triplet repeat expansion mutations described to that time, and the first identified in a GAC repeat. A unique feature of this sequence was that expansion as well as shortening of the repeat could cause the same disease. In cartilage, both patients had the rough endoplasmic reticulum inclusions in chondrocytes. These inclusions were also present in tendon tissue and could be reproduced in cultured tendon cells, suggesting that the pathophysiology of the disease is similar in both cartilage and tendon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887340" 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>Another example of disease production by expansion of a short trinucleotide repeat has been observed in the case of the polyadenylate-binding protein-2 gene (PABP2; <a href="/entry/602279">602279</a>), which is mutant in oculopharyngeal muscular dystrophy (OPMD; <a href="/entry/164300">164300</a>). In OPMD, the common (GCG)6 wildtype sequence was found to be expanded to pathologic (GCG)7-13 alleles.</p><p>Late-onset mild EDM is occasionally indistinguishable from common osteoarthritis (<a href="/entry/165720">165720</a>). Furthermore, a mutation in the C terminus of the COMP gene was reported by <a href="#5" class="mim-tip-reference" title="Briggs, M. D., Mortier, G. R., Cole, W. G., King, L. M., Golik, S. S., Bonaventure, J., Nuytinck, L., De Paepe, A., Leroy, J. G., Biesecker, L., Lipson, M., Wilcox, W. R., Lachman, R. S., Rimoin, D. L., Knowlton, R. G., Cohn, D. H. <strong>Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.</strong> Am. J. Hum. Genet. 62: 311-319, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463320</a>] [<a href="https://doi.org/10.1086/301713" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9463320">Briggs et al. (1998)</a> as producing an individual of normal height with skeletal abnormalities that included early osteoarthritis. For these reasons, <a href="#22" class="mim-tip-reference" title="Mabuchi, A., Ikeda, T., Fukuda, A., Koshizuka, Y., Hiraoka, H., Miyoshi, K., Haga, N., Kawaguchi, H., Kawakami, A., Yamamoto, S., Takatori, Y., Nakamura, K., Ikegawa, S. <strong>Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints.</strong> J. Hum. Genet. 46: 456-462, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11501943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11501943</a>] [<a href="https://doi.org/10.1007/s100380170045" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11501943">Mabuchi et al. (2001)</a> hypothesized that osteoarthritis as a common disorder may be at the mild end of the phenotypic gradation produced by COMP mutations. They ascertained the sequences of the exons and exon-intron boundaries and identified 16 polymorphisms in the COMP gene. Using 6 polymorphisms spanning the entire COMP gene, they examined the association of this gene in Japanese patients with osteoarthritis of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between osteoarthritis and control groups, and there was no significant difference in haplotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11501943+9463320" 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="#23" class="mim-tip-reference" title="Mabuchi, A., Manabe, N., Haga, N., Kitoh, H., Ikeda, T., Kawaji, H., Tamai, K., Hamada, J., Nakamura, S., Brunetti-Pierri, N., Kimizuka, M., Takatori, Y., Nakamura, K., Nishimura, G., Ohashi, H., Ikegawa, S. <strong>Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Hum. Genet. 112: 84-90, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12483304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12483304</a>] [<a href="https://doi.org/10.1007/s00439-002-0845-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12483304">Mabuchi et al. (2003)</a> reported the identification of 9 novel and 3 recurrent COMP mutations in PSACH and EDM patients. These included 2 novel types of mutations: a deletion spanning an exon-intron junction causing an exon deletion (<a href="#0015">600310.0015</a>), and a frameshift mutation resulting in a truncation of the C-terminal domain (<a href="#0016">600310.0016</a>). The remaining mutations, other than a novel exon 18 mutation, affected highly conserved aspartate or cysteine residues in the CLR region. Genotype-phenotype analysis revealed a correlation between the position and type of mutations and the severity of short stature. Mutations in the seventh CLR produced more severe short stature compared with mutations elsewhere in the CLRs and elsewhere in the COMP gene. Patients carrying mutations within the 5-aspartate repeat (amino acids 469-473) in the seventh CLR were extremely short (below -6 SD). Patients with deletion mutations were significantly shorter than those with substitution mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12483304" 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="#28" class="mim-tip-reference" title="Song, H.-R., Lee, K.-S., Li, Q.-W., Koo, S. K., Jung, S.-C. <strong>Identification of cartilage oligomeric matrix protein (COMP) gene mutations in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> J. Hum. Genet. 48: 222-225, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12768438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12768438</a>] [<a href="https://doi.org/10.1007/s10038-003-0013-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12768438">Song et al. (2003)</a> identified mutations in the COMP gene in 9 of 9 Korean patients with PSACH and in 3 of 5 Korean patients with EDM. Three of the 8 mutations identified were novel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12768438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Jakkula, E., Lohiniva, J., Capone, A., Bonafe, L., Marti, M., Schuster, V., Giedion, A., Eich, G., Boltshauser, E., Ala-Kokko, L., Superti-Furga, A. <strong>A recurrent R718W mutation in COMP results in multiple epiphyseal dysplasia with mild myopathy: clinical and pathogenetic overlap with collagen IX mutations.</strong> J. Med. Genet. 40: 942-948, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14684695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14684695</a>] [<a href="https://doi.org/10.1136/jmg.40.12.942" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14684695">Jakkula et al. (2003)</a> identified a mutation in the COMP gene (<a href="#0017">600310.0017</a>) in patients presenting with muscular weakness, a moderate rise in creatine kinase and EDM beginning in the knee joints. They suggested that the clinical and radiographic overlap between collagen IX-EDM and COMP-EDM pointed to a common supramolecular complex pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14684695" 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>Genetic diagnosis of the COMP-related skeletal dysplasias pseudoachondroplasia and multiple epiphyseal dysplasia is difficult because COMP mutations are scattered throughout the gene and 5 additional disease genes for multiple epiphyseal dysplasia exist. <a href="#24" class="mim-tip-reference" title="Mabuchi, A., Momohara, S., Ohashi, H., Takatori, Y., Haga, N., Nishimura, G., Ikegawa, S. <strong>Circulating COMP is decreased in pseudoachondroplasia and multiple epiphyseal dysplasia patients carrying COMP mutations.</strong> Am. J. Med. Genet. 129A: 35-38, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266613</a>] [<a href="https://doi.org/10.1002/ajmg.a.30164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15266613">Mabuchi et al. (2004)</a> presented evidence that plasma COMP levels are significantly decreased in patients with COMP mutations compared with controls (p less than 0.0001). In addition, plasma COMP levels were significantly decreased in EDM patients carrying mutations in COMP relative to those who lacked COMP mutations (p = 0.001). These results indicated that measuring the level of circulating COMP may be an easier, more rapid, and cost-efficient method for diagnosing PSACH and particularly for diagnosing EDM. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266613" 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>Carpal Tunnel Syndrome 2</em></strong></p><p>
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In a large 5-generation family (family 1) with carpal tunnel syndrome mapping to chromosome 19p12 (CTS2; <a href="/entry/619161">619161</a>), <a href="#19" class="mim-tip-reference" title="Li, C., Wang, N., Schaffer, A. A., Liu, X., Zhao, Z., Elliott, G., Garrett, L., Choi, N. T., Wang, Y., Wang, Y., Wang, C., Wang, J., Chan, D., Su, P., Cui, S., Yang, Y., Gao, B. <strong>Mutations in COMP cause familial carpal tunnel syndrome.</strong> Nature Commun. 11: 3642, 2020. Note: Electronic Article. Erratum: Nature Commun. 11: 3931, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32686688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32686688</a>] [<a href="https://doi.org/10.1038/s41467-020-17378-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32686688">Li et al. (2020)</a> sequenced the targeted locus and identified a heterozygous missense mutation in the COMP gene (V66E; <a href="#0019">600310.0019</a>) that segregated with disease. In a second family (family 2), in which affected individuals exhibited both CTS and EDM, whole-exome sequencing revealed heterozygosity for the R718W substitution in COMP (<a href="#0017">600310.0017</a>), a known recurrent mutation associated with EDM1. Functional analysis revealed that secretion of the R718W mutant was reduced in both primary tendon cells and chondrocytes, whereas secretion of V66E was reduced only in tendon cells; the authors noted that this might account for the different phenotypes in the 2 families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32686688" 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>To study the role of COMP in vivo, <a href="#31" class="mim-tip-reference" title="Svensson, L., Aszodi, A., Heinegard, D., Hunziker, E. B., Reinholt, F. P., Fassler, R., Oldberg, A. <strong>Cartilage oligomeric matrix protein-deficient mice have normal skeletal development.</strong> Molec. Cell. Biol. 22: 4366-4371, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12024046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12024046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12024046[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.22.12.4366-4371.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12024046">Svensson et al. (2002)</a> generated COMP-null mice and found that they showed no anatomic, histologic, or ultrastructural abnormalities associated with the pseudoachondroplasia (<a href="/entry/177170">177170</a>) or multiple epiphyseal dysplasia (<a href="/entry/132400">132400</a>) phenotypes. Northern blot and immunohistochemical analyses of cartilage indicated that the lack of COMP was not compensated for by any other member of the thrombospondin family. <a href="#31" class="mim-tip-reference" title="Svensson, L., Aszodi, A., Heinegard, D., Hunziker, E. B., Reinholt, F. P., Fassler, R., Oldberg, A. <strong>Cartilage oligomeric matrix protein-deficient mice have normal skeletal development.</strong> Molec. Cell. Biol. 22: 4366-4371, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12024046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12024046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12024046[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.22.12.4366-4371.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12024046">Svensson et al. (2002)</a> reported that the phenotype in PSACH and EDM is caused not by the reduced amount of COMP but by some other mechanism, such as folding defects or extracellular assembly abnormalities due to dysfunctional mutated COMP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12024046" 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>PSACH and EDM patients often have a mild myopathy characterized by mildly increased plasma creatine kinase levels, a variation in myofiber size and/or small atrophic fibers. <a href="#27" class="mim-tip-reference" title="Pirog, K. A., Jaka, O., Katakura, Y., Meadows, R. S., Kadler, K. E., Boot-Handford, R. P., Briggs, M. D. <strong>A mouse model offers novel insights into the myopathy and tendinopathy often associated with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Hum. Molec. Genet. 19: 52-64, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19808781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19808781</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19808781[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp466" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19808781">Pirog et al. (2010)</a> studied skeletal muscle, tendon, and ligament in a mouse model of mild PSACH harboring a T585M mutation. T585M-mutant mice exhibited a progressive muscle weakness associated with an increased number of muscle fibers with central nuclei at the perimysium and at the myotendinous junction. Collagen fibril diameters in the mutant tendons and ligaments were thicker, and tendons became more lax in cyclic strain tests. <a href="#27" class="mim-tip-reference" title="Pirog, K. A., Jaka, O., Katakura, Y., Meadows, R. S., Kadler, K. E., Boot-Handford, R. P., Briggs, M. D. <strong>A mouse model offers novel insights into the myopathy and tendinopathy often associated with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Hum. Molec. Genet. 19: 52-64, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19808781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19808781</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19808781[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp466" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19808781">Pirog et al. (2010)</a> hypothesized that the myopathy in PSACH-EDM may originate from underlying tendon and ligament pathology that may be a direct result of abnormalities in collagen fibril architecture. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19808781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using homologous recombination, <a href="#29" class="mim-tip-reference" title="Suleman, F., Gualeni, B., Gregson, H. J., Leighton, M. P., Pirog, K. A., Edwards, S., Holden, P., Boot-Handford, R. P., Briggs, M. D. <strong>A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia.</strong> Hum. Mutat. 33: 218-231, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22006726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22006726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22006726[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/humu.21631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22006726">Suleman et al. (2012)</a> generated a knock-in mouse model carrying the common D469del mutation in the COMP gene (<a href="#0004">600310.0004</a>), which is found in approximately one-third of patients with PSACH. In contrast to the human PSACH phenotype, which is a dominant disease, both copies of the mutant allele were required for the mice to develop a quantifiable chondrodysplasia phenotype. Mutant animals were normal at birth but grew slower than their wildtype littermates and developed short-limb dwarfism. In growth plates of mutant mice, chondrocyte columns were reduced in number and poorly organized, and mutant COMP was retained within the endoplasmic reticulum of cells. Chondrocyte proliferation was reduced and apoptosis was both increased and spatially dysregulated. Unlike earlier studies, <a href="#29" class="mim-tip-reference" title="Suleman, F., Gualeni, B., Gregson, H. J., Leighton, M. P., Pirog, K. A., Edwards, S., Holden, P., Boot-Handford, R. P., Briggs, M. D. <strong>A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia.</strong> Hum. Mutat. 33: 218-231, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22006726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22006726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22006726[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/humu.21631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22006726">Suleman et al. (2012)</a> observed no evidence of an unfolded protein response in this mouse model of PSACH. In contrast, microarray analysis identified expression changes in groups of genes implicated in oxidative stress, cell cycle regulation, and apoptosis, consistent with the chondrocyte pathology. <a href="#29" class="mim-tip-reference" title="Suleman, F., Gualeni, B., Gregson, H. J., Leighton, M. P., Pirog, K. A., Edwards, S., Holden, P., Boot-Handford, R. P., Briggs, M. D. <strong>A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia.</strong> Hum. Mutat. 33: 218-231, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22006726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22006726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22006726[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/humu.21631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22006726">Suleman et al. (2012)</a> suggested that a novel form of chondrocyte stress triggered by the expression of mutant COMP is central to the pathogenesis of PSACH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22006726" 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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COMP, ASP472TYR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852650 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852650;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=rs137852650" 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=rs137852650" 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=RCV000009761" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009761" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009761</a>
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<p>In a family with pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), <a href="#12" class="mim-tip-reference" title="Hecht, J. T., Nelson, L. D., Crowder, E., Wang, Y., Elder, F. F. B., Harrison, W. R., Francomano, C. A., Prange, C. K., Lennon, G. G., Deere, M., Lawler, J. <strong>Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.</strong> Nature Genet. 10: 325-329, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670471</a>] [<a href="https://doi.org/10.1038/ng0795-325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670471">Hecht et al. (1995)</a> demonstrated a G-to-T transversion at nucleotide 1439 of the COMP gene, resulting in an asp472-to-tyr amino acid substitution. The single nucleotide substitution occurred in 1 of the 5 GAC repeats, converting GAC to TAC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670471" 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>.0002 PSEUDOACHONDROPLASIA</strong>
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COMP, CYS468TYR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852651 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852651;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=rs137852651" 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=rs137852651" 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=RCV000009762 OR RCV002247283 OR RCV002512949" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009762, RCV002247283, RCV002512949" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009762...</a>
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<p>In an isolated case of pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), <a href="#12" class="mim-tip-reference" title="Hecht, J. T., Nelson, L. D., Crowder, E., Wang, Y., Elder, F. F. B., Harrison, W. R., Francomano, C. A., Prange, C. K., Lennon, G. G., Deere, M., Lawler, J. <strong>Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.</strong> Nature Genet. 10: 325-329, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670471</a>] [<a href="https://doi.org/10.1038/ng0795-325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670471">Hecht et al. (1995)</a> observed a G-to-A transition at nucleotide 1428 of the COMP gene, leading to a cys468-to-tyr amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670471" 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>.0003 PSEUDOACHONDROPLASIA</strong>
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COMP, 3-BP DEL, 459TCA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2145900868 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2145900868;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=rs2145900868" 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=rs2145900868" 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=RCV000009763" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009763" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009763</a>
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<p>In an isolated case of pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), <a href="#12" class="mim-tip-reference" title="Hecht, J. T., Nelson, L. D., Crowder, E., Wang, Y., Elder, F. F. B., Harrison, W. R., Francomano, C. A., Prange, C. K., Lennon, G. G., Deere, M., Lawler, J. <strong>Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.</strong> Nature Genet. 10: 325-329, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670471</a>] [<a href="https://doi.org/10.1038/ng0795-325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670471">Hecht et al. (1995)</a> observed deletion of nucleotides 1400-1402 (TCA) of the COMP gene, resulting in deletion of serine-459. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
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<strong>.0004 PSEUDOACHONDROPLASIA</strong>
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COMP, 3-BP DEL, 1430GAC
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193922900 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922900;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=rs193922900" 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=rs193922900" 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=RCV000033880 OR RCV000486037 OR RCV001332185" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033880, RCV000486037, RCV001332185" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033880...</a>
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<p>In 5 unrelated patients with pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), including 1 from a family originally reported by <a href="#11" class="mim-tip-reference" title="Hall, J. G., Dorst, J. P. <strong>Pseudoachondroplastic SED, recessive Maroteaux-Lamy type.</strong> Birth Defects Orig. Art. Ser. V(4): 254-259, 1969."None>Hall and Dorst (1969)</a>, <a href="#12" class="mim-tip-reference" title="Hecht, J. T., Nelson, L. D., Crowder, E., Wang, Y., Elder, F. F. B., Harrison, W. R., Francomano, C. A., Prange, C. K., Lennon, G. G., Deere, M., Lawler, J. <strong>Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.</strong> Nature Genet. 10: 325-329, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670471</a>] [<a href="https://doi.org/10.1038/ng0795-325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670471">Hecht et al. (1995)</a> identified a 3-bp deletion removing 1 of the 5 GAC repeat sequences at cDNA nucleotides 1430-1445 of the COMP gene. This resulted in the loss of an aspartate residue in a calcium-binding site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sporadic patients and affected members of 5 families with PSACH, <a href="#5" class="mim-tip-reference" title="Briggs, M. D., Mortier, G. R., Cole, W. G., King, L. M., Golik, S. S., Bonaventure, J., Nuytinck, L., De Paepe, A., Leroy, J. G., Biesecker, L., Lipson, M., Wilcox, W. R., Lachman, R. S., Rimoin, D. L., Knowlton, R. G., Cohn, D. H. <strong>Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.</strong> Am. J. Hum. Genet. 62: 311-319, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463320</a>] [<a href="https://doi.org/10.1086/301713" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9463320">Briggs et al. (1998)</a> identified heterozygosity for a 3-bp deletion (delGAC 1430-1444) in exon 13 of the COMP gene, resulting in removal of 1 of 5 consecutive aspartic acid residues corresponding to codons 469 to 473 within the seventh calmodulin-like repeat. The authors noted that the repeated nature of the GAC sequence did not allow precise determination of the codon that was deleted in the patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 sporadic patients with PSACH, <a href="#15" class="mim-tip-reference" title="Ikegawa, S., Ohashi, H., Nishimura, G., Kim, K. C., Sannohe, A., Kimizuka, M., Fukushima, Y., Nagai, T., Nakamura, Y. <strong>Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Hum. Genet. 103: 633-638, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921895</a>] [<a href="https://doi.org/10.1007/s004390050883" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921895">Ikegawa et al. (1998)</a> identified heterozygosity for a 3-bp deletion within the (GAC)5 trinucleotide repeat region in exon 13. <a href="#15" class="mim-tip-reference" title="Ikegawa, S., Ohashi, H., Nishimura, G., Kim, K. C., Sannohe, A., Kimizuka, M., Fukushima, Y., Nagai, T., Nakamura, Y. <strong>Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Hum. Genet. 103: 633-638, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921895</a>] [<a href="https://doi.org/10.1007/s004390050883" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921895">Ikegawa et al. (1998)</a> noted that, like the previously reported patients with this mutation, the phenotype was severe in all 3 patients, their adult heights being less than 110 cm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Briggs, M. D., Chapman, K. L. <strong>Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review, molecular interactions, and genotype to phenotype correlations.</strong> Hum. Mutat. 19: 465-478, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11968079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11968079</a>] [<a href="https://doi.org/10.1002/humu.10066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11968079">Briggs and Chapman (2002)</a> reviewed mutations in the COMP gene resulting in PSACH and, using nucleotide numbering from the start site of translation, designated this nucleotide change as 1405-1419 delGAC and the corresponding protein change as delD(469-473). This mutation is thought to account for approximately one-third of PSACH patients. It is a contraction of a short trinucleotide repeat; expansion of this repeat to (GAC)6 and (GAC)7 are represented by 2 other entries, <a href="#0012">600310.0012</a> and <a href="#0011">600310.0011</a>, respectively (<a href="#8" class="mim-tip-reference" title="Delot, E., King, L. M., Briggs, M. D., Wilcox, W. R., Cohn, D. H. <strong>Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene.</strong> Hum. Molec. Genet. 8: 123-128, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887340</a>] [<a href="https://doi.org/10.1093/hmg/8.1.123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887340">Delot et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9887340+11968079" 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>Mutation Function</em></strong></p><p>
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Deletion of 1 of the 5 asp codons in the type 3 calcium-binding domain of COMP essentially deletes the single asp470 spacer between calcium-binding loops 10 and 11. <a href="#18" class="mim-tip-reference" title="Kleerekoper, Q., Hecht, J. T., Putkey, J. A. <strong>Disease-causing mutations in cartilage oligomeric matrix protein cause an unstructured Ca(2+) binding domain.</strong> J. Biol. Chem. 277: 10581-10589, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11782471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11782471</a>] [<a href="https://doi.org/10.1074/jbc.M109944200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11782471">Kleerekoper et al. (2002)</a> created recombinant mutant COMP proteins that carried a deletion of asp470, mimicking the deletion found in PSACH patients, and found that this deletion decreased the calcium binding capacity of COMP. Calcium binding by this domain is required to nucleate folding. The authors predicted that persistence of the unstructured state of the mutated calcium-binding domain would lead to retention of COMP in the rough endoplasmic reticulum of differentiated PSACH and EDM1 chondrocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11782471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Dinser, R., Zaucke, F., Kreppel, F., Hultenby, K., Kochanek, S., Paulsson, M., Maurer, P. <strong>Pseudoachondroplasia is caused through both intra- and extracellular pathogenic pathways.</strong> J. Clin. Invest. 110: 505-513, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189245</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12189245[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI14386" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189245">Dinser et al. (2002)</a> developed a cell culture model of pseudoachondroplasia by expressing mutant COMP (D469del) in bovine primary chondrocytes. They showed that mutant COMP exerts its deleterious effects through both intra- and extracellular pathogenic pathways. Overexpression of mutant COMP led to a dose-dependent decrease in cellular viability. The secretion of mutant COMP was markedly delayed, presumably due to a prolonged association with chaperones in the endoplasmic reticulum. The extracellular matrix lacked organized collagen fibers and showed amorphous aggregates formed by mutant COMP. Thus, pseudoachondroplasia appeared to be an endoplasmic reticulum storage disease, most likely caused by improper folding of mutant COMP. The growth failure of patients with pseudoachondroplasia may be explained by an increased cell death of growth-plate chondrocytes. Dominant interference of the mutant protein with collagen fiber assembly could contribute to the observed failure of the extracellular matrix of cartilage and tendons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12189245" 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, 1, SEVERE</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">rs137852652 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852652;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=rs137852652" 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=rs137852652" 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=RCV000009765" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009765" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009765</a>
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<p>In a patient with a severe form of multiple epiphyseal dysplasia-1 (EDM1; <a href="/entry/132400">132400</a>), <a href="#4" class="mim-tip-reference" title="Briggs, M. D., Hoffman, S. M. G., King, L. M., Olsen, A. S., Mohrenweiser, H., Leroy, J. G., Mortier, G. R., Rimoin, D. L., Lachman, R. S., Gaines, E. S., Cekleniak, J. A., Knowlton, R. G., Cohn, D. H. <strong>Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.</strong> Nature Genet. 10: 330-336, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670472</a>] [<a href="https://doi.org/10.1038/ng0795-330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670472">Briggs et al. (1995)</a> identified a de novo heterozygous mutation in the COMP gene, resulting in an asp342-to-tyr (D342Y) substitution in a conserved residue in the third calmodulin-like repeat. The mutation created an RsaI restriction endonuclease cleavage site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670472" 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 PSEUDOACHONDROPLASIA</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">rs137852653 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852653;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=rs137852653" 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=rs137852653" 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=RCV000009766" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009766" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009766</a>
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<p>In an affected individual from a family with a moderately severe form of pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), <a href="#4" class="mim-tip-reference" title="Briggs, M. D., Hoffman, S. M. G., King, L. M., Olsen, A. S., Mohrenweiser, H., Leroy, J. G., Mortier, G. R., Rimoin, D. L., Lachman, R. S., Gaines, E. S., Cekleniak, J. A., Knowlton, R. G., Cohn, D. H. <strong>Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.</strong> Nature Genet. 10: 330-336, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670472</a>] [<a href="https://doi.org/10.1038/ng0795-330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670472">Briggs et al. (1995)</a> found heterozygosity for a point mutation that predicted substitution of arginine for the cysteine at residue 328 (cys328-to-arg; C328R). The mutation altered a conserved residue in the second calmodulin-like repeat of COMP. The change created a new cleavage site which was identified in genomic DNA in all 4 affected members of the family but in no unaffected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 MOVED TO <a href="/entry/600310#0004">600310.0004</a></strong>
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<strong>.0008 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1, MILD</strong>
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COMP, ASN523LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852654 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852654;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=rs137852654" 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=rs137852654" 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=RCV000009767 OR RCV001851774 OR RCV002054430" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009767, RCV001851774, RCV002054430" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009767...</a>
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<p>In affected members of a South African family with a mild form of multiple epiphyseal dysplasia-1 (EDM1; <a href="/entry/132400">132400</a>), <a href="#2" class="mim-tip-reference" title="Ballo, R., Briggs, M. D., Cohn, D. H., Knowlton, R. G., Beighton, P. H., Ramesar, R. S. <strong>Multiple epiphyseal dysplasia, Ribbing type: a novel point mutation in the COMP gene in a South African family.</strong> Am. J. Med. Genet. 68: 396-400, 1997. Note: Erratum: Am. J. Med. Genet. 71: 494 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9021009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9021009</a>]" pmid="9021009">Ballo et al. (1997)</a> identified a heterozygous 1594C-G transversion in the COMP gene, resulting in an asn523-to-lys (N523K) substitution, which altered a residue at the C-terminal end of the calmodulin-like region of the protein. There were affected individuals in 3 generations. Radiologic findings in a mother and son included flattening and irregularity of femoral heads and unevenness of the intraarticular aspects of the distal end of the femurs and proximal end of the tibias. The lateral femoral condyles were hypoplastic. The endplates of the vertebral bodies showed mild sclerosis and irregularity, but there was no significant flattening. <a href="#2" class="mim-tip-reference" title="Ballo, R., Briggs, M. D., Cohn, D. H., Knowlton, R. G., Beighton, P. H., Ramesar, R. S. <strong>Multiple epiphyseal dysplasia, Ribbing type: a novel point mutation in the COMP gene in a South African family.</strong> Am. J. Med. Genet. 68: 396-400, 1997. Note: Erratum: Am. J. Med. Genet. 71: 494 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9021009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9021009</a>]" pmid="9021009">Ballo et al. (1997)</a> stated that the identification of this mutation demonstrates that the spectrum of manifestations from mild EDM through pseudoachondroplasia can all be produced by structural mutations in COMP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9021009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1, SEVERE</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">rs28936668 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28936668;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=rs28936668" 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=rs28936668" 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=RCV000009768" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009768" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009768</a>
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<p>In a patient (family R94-344) with a severe form of multiple epiphyseal dysplasia-1 (EDM1; <a href="/entry/132400">132400</a>), <a href="#5" class="mim-tip-reference" title="Briggs, M. D., Mortier, G. R., Cole, W. G., King, L. M., Golik, S. S., Bonaventure, J., Nuytinck, L., De Paepe, A., Leroy, J. G., Biesecker, L., Lipson, M., Wilcox, W. R., Lachman, R. S., Rimoin, D. L., Knowlton, R. G., Cohn, D. H. <strong>Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.</strong> Am. J. Hum. Genet. 62: 311-319, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463320</a>] [<a href="https://doi.org/10.1086/301713" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9463320">Briggs et al. (1998)</a> found a 1383A-G transition in exon 13 of the COMP gene which resulted in an asn453-to-ser (N453S) amino acid substitution located in the calmodulin-like domain 7. The proband was first seen at the age of 15 years when she was short of stature (height 144 cm) and complained of pain in the knees. The hands were normal. Radiographs showed normal hands and hips, but the tibial epiphyses were irregular, with a squared aspect. Her affected sister was also short of stature and had involvement of the knees and hips. The femoral head was small and irregular, but the severity of the deformities was somewhat less striking than those of other cases of EDM Fairbank. The affected father had knee involvement but the hips were unaffected. The affected grandmother had severe hip dysplasia that required surgical replacement of the femoral head. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 PSEUDOACHONDROPLASIA</strong>
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COMP, ASP473GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28936669 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28936669;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=rs28936669" 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=rs28936669" 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=RCV000009769" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009769" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009769</a>
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<p>In a sporadic case of pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), <a href="#14" class="mim-tip-reference" title="Ikegawa, S., Ohashi, H., Hosoda, F., Fukushima, Y., Ohki, M., Nakamura, Y. <strong>Pseudoachondroplasia with de novo deletion [del(11)(q21q22.2)].</strong> Am. J. Med. Genet. 77: 356-359, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9632164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9632164</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19980605)77:5<356::aid-ajmg3>3.0.co;2-l" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9632164">Ikegawa et al. (1998)</a> described an interstitial deletion in 11q. In a subsequent sequence analysis, (<a href="#16" class="mim-tip-reference" title="Ikegawa, S. <strong>Personal Communication.</strong> Tokyo, Japan 11/30/1998."None>Ikegawa, 1998</a>) identified a 1418A-G transition in the COMP gene, resulting in an asp473-to-gly (D473G) amino acid substitution. The deletion was apparently fortuitous; since the mutation was de novo (absent in the normal parents) and substituted a highly conserved aspartic acid residue, it was presumably the cause of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9632164" 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>.0011 PSEUDOACHONDROPLASIA</strong>
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COMP, 6-BP INS, (GAC)7
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009770 OR RCV004730840" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009770, RCV004730840" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009770...</a>
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<p>In a sporadic case of pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), <a href="#8" class="mim-tip-reference" title="Delot, E., King, L. M., Briggs, M. D., Wilcox, W. R., Cohn, D. H. <strong>Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene.</strong> Hum. Molec. Genet. 8: 123-128, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887340</a>] [<a href="https://doi.org/10.1093/hmg/8.1.123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887340">Delot et al. (1999)</a> identified an expansion of the short trinucleotide repeat, (GAC)5, located at cDNA dinucleotides 1430 to 1444 of the COMP gene. The patient was found to be heterozygous for a (GAC)7 allele. The diagnosis of typical PSACH had been established at 3 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887340" 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>.0012 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1</strong>
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COMP, 3-BP INS, (GAC)6
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193922900 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922900;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=rs193922900" 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=rs193922900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009771 OR RCV000033881 OR RCV001090556 OR RCV002054431" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009771, RCV000033881, RCV001090556, RCV002054431" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009771...</a>
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<p>In a patient with multiple epiphyseal dysplasia-1 (EDM1; <a href="/entry/132400">132400</a>) from a family with autosomal dominant inheritance, <a href="#8" class="mim-tip-reference" title="Delot, E., King, L. M., Briggs, M. D., Wilcox, W. R., Cohn, D. H. <strong>Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene.</strong> Hum. Molec. Genet. 8: 123-128, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887340</a>] [<a href="https://doi.org/10.1093/hmg/8.1.123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887340">Delot et al. (1999)</a> found an expansion of the short (GAC)5 repeat; the patient was heterozygous for a (GAC)6 allele. The diagnosis of EDM1 had been established at the age of 13 years; she was noted to have short stature and radiographic abnormalities confined to the epiphyses of the long bones. The affected mother had undergone surgery to replace the left and right hips at 35 and 37 years of age, respectively. The adult height of the proband was 153 cm and her affected mother was 160 cm tall. By comparison, 2 unaffected females in the family were 168 and 173 cm tall. A brother was more severely affected and underwent bilateral osteotomies at 16 years of age for genu varum. The proband underwent hip replacement surgery at age 34, at which time cartilage and tendon from the femoral head were obtained. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887340" 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>.0013 PSEUDOACHONDROPLASIA, SEVERE</strong>
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COMP, GLY719ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852655 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852655;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=rs137852655" 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=rs137852655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009772 OR RCV000033890 OR RCV002223755 OR RCV003989283" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009772, RCV000033890, RCV002223755, RCV003989283" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009772...</a>
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<p><a href="#21" class="mim-tip-reference" title="Mabuchi, A., Haga, N., Ikeda, T., Manabe, N., Ohashi, H., Takatori, Y., Nakamura, K., Ikegawa, S. <strong>Novel mutation in exon 18 of the cartilage oligomeric matrix protein gene causes a severe pseudoachondroplasia.</strong> Am. J. Med. Genet. 104: 135-139, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11746044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11746044</a>] [<a href="https://doi.org/10.1002/ajmg.10067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11746044">Mabuchi et al. (2001)</a> reported a case with severe pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), including marked short stature and deformities of the spine and extremities. The patient had a G-to-A transition (GGT-GAT) at nucleotide 2156 in exon 18 of the COMP gene. The mutation was predicted to cause a gly719-to-asp (G719D) substitution in the C-terminal globular domain and was the first case with a severe pseudoachondroplasia phenotype with a mutation outside the seventh calmodulin-like repeat. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11746044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0014" class="mim-anchor"></a>
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<strong>.0014 PSEUDOACHONDROPLASIA</strong>
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COMP, CYS348ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852656 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852656;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=rs137852656" 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=rs137852656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009773 OR RCV003555993" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009773, RCV003555993" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009773...</a>
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<p><a href="#33" class="mim-tip-reference" title="Unger, S., Korkko, J., Krakow, D., Lachman, R. S., Rimoin, D. L., Cohn, D. H. <strong>Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal dysplasia congenita.</strong> Am. J. Med. Genet. 104: 140-146, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11746045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11746045</a>] [<a href="https://doi.org/10.1002/ajmg.10062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11746045">Unger et al. (2001)</a> reported a child with double heterozygosity for pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), resulting from a cys348-to-arg mutation in the COMP gene, and spondyloepiphyseal dysplasia congenita (<a href="/entry/183900">183900</a>), resulting from a mutation in the COL2A1 gene (<a href="/entry/120140#0035">120140.0035</a>). The child inherited pseudoachondroplasia from his mother and spondyloepiphyseal dysplasia congenita from his father. He had clinical and radiographic findings that were more severe than those in either disorder alone. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11746045" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0015" class="mim-anchor"></a>
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<h4>
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<strong>.0015 PSEUDOACHONDROPLASIA</strong>
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COMP, 533-BP DEL, EX9
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2145902395 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2145902395;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=rs2145902395" 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=rs2145902395" 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=RCV000009774" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009774" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009774</a>
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<p><a href="#23" class="mim-tip-reference" title="Mabuchi, A., Manabe, N., Haga, N., Kitoh, H., Ikeda, T., Kawaji, H., Tamai, K., Hamada, J., Nakamura, S., Brunetti-Pierri, N., Kimizuka, M., Takatori, Y., Nakamura, K., Nishimura, G., Ohashi, H., Ikegawa, S. <strong>Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Hum. Genet. 112: 84-90, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12483304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12483304</a>] [<a href="https://doi.org/10.1007/s00439-002-0845-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12483304">Mabuchi et al. (2003)</a> described a 533-bp deletion extending from exon 9 to intron 9 of the COMP gene in a patient with severe pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>); his height was below -8 SD and his joint involvement was multiple and severe. The aberrant allele would significantly affect the conformation of the COMP protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12483304" 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>.0016 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1, MILD</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">rs869320730 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869320730;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=rs869320730" 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=rs869320730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient (MED5) with a mild form of multiple epiphyseal dysplasia-1 (EDM1; <a href="/entry/132400">132400</a>), <a href="#23" class="mim-tip-reference" title="Mabuchi, A., Manabe, N., Haga, N., Kitoh, H., Ikeda, T., Kawaji, H., Tamai, K., Hamada, J., Nakamura, S., Brunetti-Pierri, N., Kimizuka, M., Takatori, Y., Nakamura, K., Nishimura, G., Ohashi, H., Ikegawa, S. <strong>Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Hum. Genet. 112: 84-90, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12483304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12483304</a>] [<a href="https://doi.org/10.1007/s00439-002-0845-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12483304">Mabuchi et al. (2003)</a> described a cytosine inserted between nucleotides 2223 and 2224 in the C-terminal part of the COMP gene. The insertion changed codon 742 from AAT (asn) to CAA (gln) with a frameshift that changed codon 743 from GAC (asp) to TGA (ter); the mutation was symbolized Asn742fsTer743. Asn742, the first affected amino acid, is the predicted site for N-linked glycosylation. The insertion caused premature termination of the codon and a truncated COMP protein. The mutation was located immediately following cys741. Although the frameshift mutation was predicted to produce a considerably truncated protein (15 amino acids shorter), the phenotypic effect was mild. Members of the family showed involvement of the hip and knee joints, but their stature was normal. Therefore, the sequence following cys741 may have little impact for COMP function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12483304" 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> rs28936368 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28936368;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/rs28936368?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=rs28936368" 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=rs28936368" 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=RCV000009776 OR RCV001268837 OR RCV001289465 OR RCV002054432" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009776, RCV001268837, RCV001289465, RCV002054432" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009776...</a>
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<p><strong><em>Multiple Epiphyseal Dysplasia 1</em></strong></p><p>
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In a patient with a severe form of multiple epiphyseal dysplasia-1 (EDM1; <a href="/entry/132400">132400</a>), <a href="#23" class="mim-tip-reference" title="Mabuchi, A., Manabe, N., Haga, N., Kitoh, H., Ikeda, T., Kawaji, H., Tamai, K., Hamada, J., Nakamura, S., Brunetti-Pierri, N., Kimizuka, M., Takatori, Y., Nakamura, K., Nishimura, G., Ohashi, H., Ikegawa, S. <strong>Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong> Hum. Genet. 112: 84-90, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12483304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12483304</a>] [<a href="https://doi.org/10.1007/s00439-002-0845-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12483304">Mabuchi et al. (2003)</a> identified a 2152C-T transition in exon 18 of the COMP gene, resulting in an arg718-to-trp (R718W) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12483304" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Jakkula, E., Lohiniva, J., Capone, A., Bonafe, L., Marti, M., Schuster, V., Giedion, A., Eich, G., Boltshauser, E., Ala-Kokko, L., Superti-Furga, A. <strong>A recurrent R718W mutation in COMP results in multiple epiphyseal dysplasia with mild myopathy: clinical and pathogenetic overlap with collagen IX mutations.</strong> J. Med. Genet. 40: 942-948, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14684695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14684695</a>] [<a href="https://doi.org/10.1136/jmg.40.12.942" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14684695">Jakkula et al. (2003)</a> identified the same mutation in patients with EDM1 who had muscle weakness, moderate creatine kinase elevation, and EDM beginning with the knee joints. No disease-causing mutations were detected in collagen IX genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14684695" 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>Carpal Tunnel Syndrome 2</em></strong></p><p>
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In affected members of a large 4-generation family (family 2) with carpal tunnel syndrome (CTS2; <a href="/entry/619161">619161</a>) as well as signs of EDM, <a href="#19" class="mim-tip-reference" title="Li, C., Wang, N., Schaffer, A. A., Liu, X., Zhao, Z., Elliott, G., Garrett, L., Choi, N. T., Wang, Y., Wang, Y., Wang, C., Wang, J., Chan, D., Su, P., Cui, S., Yang, Y., Gao, B. <strong>Mutations in COMP cause familial carpal tunnel syndrome.</strong> Nature Commun. 11: 3642, 2020. Note: Electronic Article. Erratum: Nature Commun. 11: 3931, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32686688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32686688</a>] [<a href="https://doi.org/10.1038/s41467-020-17378-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32686688">Li et al. (2020)</a> identified heterozygosity for the c.2152C-T transition (c.2152C-T, NM_000095.3) in the COMP gene resulting in the R718W mutation. The mutation segregated fully with disease in the family and was not found in human genome variation databases. Functional analysis showed that secretion of the R718W mutant was reduced in both primary tendon cells and chondrocytes compared to wildtype COMP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32686688" 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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COMP, 3-BP DEL, 1139GAC
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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> rs1198060288 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1198060288;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/rs1198060288?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=rs1198060288" 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=rs1198060288" 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=RCV001901762 OR RCV002259406 OR RCV002290796" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001901762, RCV002259406, RCV002290796" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001901762...</a>
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<p>In an individual with moderately severe pseudoachondroplasia (PSACH; <a href="/entry/177170">177170</a>), <a href="#4" class="mim-tip-reference" title="Briggs, M. D., Hoffman, S. M. G., King, L. M., Olsen, A. S., Mohrenweiser, H., Leroy, J. G., Mortier, G. R., Rimoin, D. L., Lachman, R. S., Gaines, E. S., Cekleniak, J. A., Knowlton, R. G., Cohn, D. H. <strong>Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.</strong> Nature Genet. 10: 330-336, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670472</a>] [<a href="https://doi.org/10.1038/ng0795-330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670472">Briggs et al. (1995)</a> identified heterozygosity for a 3-bp deletion in exon 10 of the COMP gene, which eliminated a codon for an aspartic acid residue from the (GAC)3 repeat within the fourth calmodulin-like repeat. Due to the repeated sequence of nucleotides 1139-1147, it was not possible to determine which 3 nucleotides were deleted and, hence, which aspartic acid codon (372-374) was eliminated. The occurrence of the deletion in a series of direct repeats suggested that the mutation resulted from slipped mispairing during DNA replication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with typical PSACH, <a href="#5" class="mim-tip-reference" title="Briggs, M. D., Mortier, G. R., Cole, W. G., King, L. M., Golik, S. S., Bonaventure, J., Nuytinck, L., De Paepe, A., Leroy, J. G., Biesecker, L., Lipson, M., Wilcox, W. R., Lachman, R. S., Rimoin, D. L., Knowlton, R. G., Cohn, D. H. <strong>Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.</strong> Am. J. Hum. Genet. 62: 311-319, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463320</a>] [<a href="https://doi.org/10.1086/301713" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9463320">Briggs et al. (1998)</a> identified heterozygosity for a 3-bp deletion (delGAC 1139-1147) in the COMP gene. Chondrocytes from the patient showed the characteristic lamellar inclusions of the rough endoplasmic reticulum observed in PSACH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Briggs, M. D., Chapman, K. L. <strong>Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review, molecular interactions, and genotype to phenotype correlations.</strong> Hum. Mutat. 19: 465-478, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11968079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11968079</a>] [<a href="https://doi.org/10.1002/humu.10066" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11968079">Briggs and Chapman (2002)</a> reviewed mutations in the COMP gene resulting in PSACH and, using nucleotide numbering from the start site of translation, designated this nucleotide change as 1114-1122 delGAC and the corresponding protein change as delD(372-374). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11968079" 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">rs2055205599 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2055205599;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=rs2055205599" 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=rs2055205599" 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=RCV001289466" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001289466" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001289466</a>
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<p>In affected members of a large 5-generation family (family 1) with carpal tunnel syndrome mapping to chromosome 19p12 (CTS2; <a href="/entry/619161">619161</a>), <a href="#19" class="mim-tip-reference" title="Li, C., Wang, N., Schaffer, A. A., Liu, X., Zhao, Z., Elliott, G., Garrett, L., Choi, N. T., Wang, Y., Wang, Y., Wang, C., Wang, J., Chan, D., Su, P., Cui, S., Yang, Y., Gao, B. <strong>Mutations in COMP cause familial carpal tunnel syndrome.</strong> Nature Commun. 11: 3642, 2020. Note: Electronic Article. Erratum: Nature Commun. 11: 3931, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32686688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32686688</a>] [<a href="https://doi.org/10.1038/s41467-020-17378-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32686688">Li et al. (2020)</a> identified heterozygosity for a c.197T-A transversion (c.197T-A, NM_000095.3) in exon 3 of the COMP gene, resulting in a val66-to-glu (V66E) substitution within the N-terminal homopentamer-forming coiled-coil domain. The mutation segregated fully with disease in the family and was not found in human genome variation databases. Functional studies showed that secretion of the V66E mutant was reduced in primary tendon cells, whereas secretion in chondrocytes was as efficient as wildtype COMP. Fractionation analysis revealed that the V66E substitution disrupts COMP pentamerization, and the mutant COMP did not colocalize with type I collagen (see <a href="/entry/120150">120150</a>) in the extracellular matrix (ECM), suggesting that proper oligomerization is important for sufficient COMP secretion in primary tendon cells and integration into the ECM protein complex. Coexpression of wildtype and mutant COMP in primary tendon cells showed that the V66E mutant impaired the secretion of wildtype COMP, indicating a dominant-negative effect. In a knockin mouse model of a V65E Comp mutation, equivalent to the human V66E mutation, the authors observed reduced ability to repair tendon damage compared to wildtype or Comp -/- mice, also consistent with a dominant-negative effect. Ultrastructural and immunohistochemical analysis of patient tendon cells showed evidence of increased endoplasmic reticulum stress and tendon/ligament cell death, associated with inflammatory cells and fibrosis, which the authors noted might further impair ECM architecture. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32686688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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|
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|
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<li>
|
|
<a id="1" class="mim-anchor"></a>
|
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<a id="Agarwal2012" class="mim-anchor"></a>
|
|
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|
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Agarwal, P., Zwolanek, D., Keene, D. R., Schulz, J.-N., Blumbach, K., Heinegard, D., Zaucke, F., Paulsson, M., Krieg, T., Koch, M., Eckes, B.
|
|
<strong>Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure.</strong>
|
|
J. Biol. Chem. 287: 22549-22559, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22573329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22573329</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22573329[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=22573329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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[<a href="https://doi.org/10.1074/jbc.M111.335935" target="_blank">Full Text</a>]
|
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</p>
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|
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<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Ballo1997" class="mim-anchor"></a>
|
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|
|
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|
|
Ballo, R., Briggs, M. D., Cohn, D. H., Knowlton, R. G., Beighton, P. H., Ramesar, R. S.
|
|
<strong>Multiple epiphyseal dysplasia, Ribbing type: a novel point mutation in the COMP gene in a South African family.</strong>
|
|
Am. J. Med. Genet. 68: 396-400, 1997. Note: Erratum: Am. J. Med. Genet. 71: 494 only, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9021009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9021009</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9021009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
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|
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<a id="Briggs2002" class="mim-anchor"></a>
|
|
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|
|
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|
|
Briggs, M. D., Chapman, K. L.
|
|
<strong>Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review, molecular interactions, and genotype to phenotype correlations.</strong>
|
|
Hum. Mutat. 19: 465-478, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11968079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11968079</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11968079" 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/humu.10066" target="_blank">Full Text</a>]
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|
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|
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|
|
</li>
|
|
|
|
<li>
|
|
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|
|
<a id="Briggs1995" class="mim-anchor"></a>
|
|
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|
|
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|
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Briggs, M. D., Hoffman, S. M. G., King, L. M., Olsen, A. S., Mohrenweiser, H., Leroy, J. G., Mortier, G. R., Rimoin, D. L., Lachman, R. S., Gaines, E. S., Cekleniak, J. A., Knowlton, R. G., Cohn, D. H.
|
|
<strong>Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.</strong>
|
|
Nature Genet. 10: 330-336, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670472</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670472" 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/ng0795-330" target="_blank">Full Text</a>]
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|
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<a id="Briggs1998" class="mim-anchor"></a>
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Briggs, M. D., Mortier, G. R., Cole, W. G., King, L. M., Golik, S. S., Bonaventure, J., Nuytinck, L., De Paepe, A., Leroy, J. G., Biesecker, L., Lipson, M., Wilcox, W. R., Lachman, R. S., Rimoin, D. L., Knowlton, R. G., Cohn, D. H.
|
|
<strong>Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.</strong>
|
|
Am. J. Hum. Genet. 62: 311-319, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9463320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9463320</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9463320" 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/10.1086/301713" target="_blank">Full Text</a>]
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|
|
</li>
|
|
|
|
<li>
|
|
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<a id="Deere1998" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
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Deere, M., Sanford, T., Ferguson, H. L., Daniels, K., Hecht, J. T.
|
|
<strong>Identification of twelve mutations in cartilage oligomeric matrix protein (COMP) in patients with pseudoachondroplasia.</strong>
|
|
Am. J. Med. Genet. 80: 510-513, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9880218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9880218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9880218" 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/(sici)1096-8628(19981228)80:5<510::aid-ajmg14>3.0.co;2-f" target="_blank">Full Text</a>]
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|
</li>
|
|
|
|
<li>
|
|
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<a id="Deere1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
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Deere, M., Sanford, T., Francomano, C. A., Daniels, K., Hecht, J. T.
|
|
<strong>Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
Am. J. Med. Genet. 85: 486-490, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10405447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10405447</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10405447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1002/(sici)1096-8628(19990827)85:5<486::aid-ajmg10>3.0.co;2-o" target="_blank">Full Text</a>]
|
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|
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|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
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<a id="Delot1999" class="mim-anchor"></a>
|
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<div class="">
|
|
<p class="mim-text-font">
|
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Delot, E., King, L. M., Briggs, M. D., Wilcox, W. R., Cohn, D. H.
|
|
<strong>Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene.</strong>
|
|
Hum. Molec. Genet. 8: 123-128, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1093/hmg/8.1.123" target="_blank">Full Text</a>]
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|
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|
|
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|
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|
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<a id="Dinser2002" class="mim-anchor"></a>
|
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|
|
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|
|
Dinser, R., Zaucke, F., Kreppel, F., Hultenby, K., Kochanek, S., Paulsson, M., Maurer, P.
|
|
<strong>Pseudoachondroplasia is caused through both intra- and extracellular pathogenic pathways.</strong>
|
|
J. Clin. Invest. 110: 505-513, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189245</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12189245[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=12189245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1172/JCI14386" target="_blank">Full Text</a>]
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|
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|
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<a id="10" class="mim-anchor"></a>
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<a id="Halasz2007" class="mim-anchor"></a>
|
|
<div class="">
|
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|
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Halasz, K., Kassner, A., Morgelin, M., Heinegard, D.
|
|
<strong>COMP acts as a catalyst in collagen fibrillogenesis.</strong>
|
|
J. Biol. Chem. 282: 31166-31173, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17716974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17716974</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17716974" 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/10.1074/jbc.M705735200" target="_blank">Full Text</a>]
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|
|
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|
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|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
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<a id="Hall1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
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|
|
Hall, J. G., Dorst, J. P.
|
|
<strong>Pseudoachondroplastic SED, recessive Maroteaux-Lamy type.</strong>
|
|
Birth Defects Orig. Art. Ser. V(4): 254-259, 1969.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
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</li>
|
|
|
|
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|
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<a id="Hecht1995" class="mim-anchor"></a>
|
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|
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Hecht, J. T., Nelson, L. D., Crowder, E., Wang, Y., Elder, F. F. B., Harrison, W. R., Francomano, C. A., Prange, C. K., Lennon, G. G., Deere, M., Lawler, J.
|
|
<strong>Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.</strong>
|
|
Nature Genet. 10: 325-329, 1995.
|
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670471</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670471" 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/ng0795-325" target="_blank">Full Text</a>]
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<a id="Holden2001" class="mim-anchor"></a>
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|
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|
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Holden, P., Meadows, R. S., Chapman, K. L., Grant, M. E., Kadler, K. E., Briggs, M. D.
|
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<strong>Cartilage oligomeric matrix protein interacts with type IX collagen, and disruptions to these interactions identify a pathogenetic mechanism in a bone dysplasia family.</strong>
|
|
J. Biol. Chem. 276: 6046-6055, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11087755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11087755</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11087755" 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/10.1074/jbc.M009507200" target="_blank">Full Text</a>]
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|
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<a id="Ikegawa1998" class="mim-anchor"></a>
|
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|
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|
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Ikegawa, S., Ohashi, H., Hosoda, F., Fukushima, Y., Ohki, M., Nakamura, Y.
|
|
<strong>Pseudoachondroplasia with de novo deletion [del(11)(q21q22.2)].</strong>
|
|
Am. J. Med. Genet. 77: 356-359, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9632164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9632164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9632164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1002/(sici)1096-8628(19980605)77:5<356::aid-ajmg3>3.0.co;2-l" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Ikegawa1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ikegawa, S., Ohashi, H., Nishimura, G., Kim, K. C., Sannohe, A., Kimizuka, M., Fukushima, Y., Nagai, T., Nakamura, Y.
|
|
<strong>Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
Hum. Genet. 103: 633-638, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s004390050883" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Ikegawa1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ikegawa, S.
|
|
<strong>Personal Communication.</strong>
|
|
Tokyo, Japan 11/30/1998.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Jakkula2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jakkula, E., Lohiniva, J., Capone, A., Bonafe, L., Marti, M., Schuster, V., Giedion, A., Eich, G., Boltshauser, E., Ala-Kokko, L., Superti-Furga, A.
|
|
<strong>A recurrent R718W mutation in COMP results in multiple epiphyseal dysplasia with mild myopathy: clinical and pathogenetic overlap with collagen IX mutations.</strong>
|
|
J. Med. Genet. 40: 942-948, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14684695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14684695</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14684695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.40.12.942" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Kleerekoper2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kleerekoper, Q., Hecht, J. T., Putkey, J. A.
|
|
<strong>Disease-causing mutations in cartilage oligomeric matrix protein cause an unstructured Ca(2+) binding domain.</strong>
|
|
J. Biol. Chem. 277: 10581-10589, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11782471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11782471</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11782471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M109944200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Li2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, C., Wang, N., Schaffer, A. A., Liu, X., Zhao, Z., Elliott, G., Garrett, L., Choi, N. T., Wang, Y., Wang, Y., Wang, C., Wang, J., Chan, D., Su, P., Cui, S., Yang, Y., Gao, B.
|
|
<strong>Mutations in COMP cause familial carpal tunnel syndrome.</strong>
|
|
Nature Commun. 11: 3642, 2020. Note: Electronic Article. Erratum: Nature Commun. 11: 3931, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32686688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32686688</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32686688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/s41467-020-17378-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Liu2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liu, C., Kong, W., Ilalov, K., Yu, S., Xu, K., Prazak, L., Fajardo, M., Sehgal, B., Di Cesare, P. E.
|
|
<strong>ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein.</strong>
|
|
FASEB J. 20: 988-990, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16585064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16585064</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16585064[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=16585064" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1096/fj.05-3877fje" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Mabuchi2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mabuchi, A., Haga, N., Ikeda, T., Manabe, N., Ohashi, H., Takatori, Y., Nakamura, K., Ikegawa, S.
|
|
<strong>Novel mutation in exon 18 of the cartilage oligomeric matrix protein gene causes a severe pseudoachondroplasia.</strong>
|
|
Am. J. Med. Genet. 104: 135-139, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11746044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11746044</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11746044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.10067" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Mabuchi2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mabuchi, A., Ikeda, T., Fukuda, A., Koshizuka, Y., Hiraoka, H., Miyoshi, K., Haga, N., Kawaguchi, H., Kawakami, A., Yamamoto, S., Takatori, Y., Nakamura, K., Ikegawa, S.
|
|
<strong>Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints.</strong>
|
|
J. Hum. Genet. 46: 456-462, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11501943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11501943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11501943" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s100380170045" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Mabuchi2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mabuchi, A., Manabe, N., Haga, N., Kitoh, H., Ikeda, T., Kawaji, H., Tamai, K., Hamada, J., Nakamura, S., Brunetti-Pierri, N., Kimizuka, M., Takatori, Y., Nakamura, K., Nishimura, G., Ohashi, H., Ikegawa, S.
|
|
<strong>Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
Hum. Genet. 112: 84-90, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12483304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12483304</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12483304" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00439-002-0845-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Mabuchi2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mabuchi, A., Momohara, S., Ohashi, H., Takatori, Y., Haga, N., Nishimura, G., Ikegawa, S.
|
|
<strong>Circulating COMP is decreased in pseudoachondroplasia and multiple epiphyseal dysplasia patients carrying COMP mutations.</strong>
|
|
Am. J. Med. Genet. 129A: 35-38, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15266613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15266613</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15266613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.30164" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Maddox2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maddox, B. K., Mokashi, A., Keene, D. R., Bachinger, H. P.
|
|
<strong>A cartilage oligomeric matrix protein mutation associated with pseudoachondroplasia changes the structural and functional properties of the type 3 domain.</strong>
|
|
J. Biol. Chem. 275: 11412-11417, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10753957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10753957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10753957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.275.15.11412" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Newton1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Newton, G., Weremowicz, S., Morton, C. C., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Lawler, J.
|
|
<strong>Characterization of human and mouse cartilage oligomeric matrix protein.</strong>
|
|
Genomics 24: 435-439, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7713493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7713493</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7713493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1649" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Pirog2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pirog, K. A., Jaka, O., Katakura, Y., Meadows, R. S., Kadler, K. E., Boot-Handford, R. P., Briggs, M. D.
|
|
<strong>A mouse model offers novel insights into the myopathy and tendinopathy often associated with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
Hum. Molec. Genet. 19: 52-64, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19808781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19808781</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19808781[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=19808781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp466" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Song2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Song, H.-R., Lee, K.-S., Li, Q.-W., Koo, S. K., Jung, S.-C.
|
|
<strong>Identification of cartilage oligomeric matrix protein (COMP) gene mutations in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
J. Hum. Genet. 48: 222-225, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12768438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12768438</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12768438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10038-003-0013-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Suleman2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Suleman, F., Gualeni, B., Gregson, H. J., Leighton, M. P., Pirog, K. A., Edwards, S., Holden, P., Boot-Handford, R. P., Briggs, M. D.
|
|
<strong>A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia.</strong>
|
|
Hum. Mutat. 33: 218-231, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22006726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22006726</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22006726[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=22006726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.21631" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Susic1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Susic, S., McGrory, J., Ahier, J., Cole, W. G.
|
|
<strong>Multiple epiphyseal dysplasia and pseudoachondroplasia due to novel mutations in the calmodulin-like repeats of cartilage oligomeric matrix protein.</strong>
|
|
Clin. Genet. 51: 219-224, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9184241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9184241</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9184241" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1997.tb02458.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Svensson2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Svensson, L., Aszodi, A., Heinegard, D., Hunziker, E. B., Reinholt, F. P., Fassler, R., Oldberg, A.
|
|
<strong>Cartilage oligomeric matrix protein-deficient mice have normal skeletal development.</strong>
|
|
Molec. Cell. Biol. 22: 4366-4371, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12024046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12024046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12024046[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=12024046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1128/MCB.22.12.4366-4371.2002" 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="32" class="mim-anchor"></a>
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<a id="Thur2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Thur, J., Rosenberg, K., Nitsche, D. P., Pihlajamaa, T., Ala-Kokko, L., Heinegard, D., Paulsson, M., Maurer, P.
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|
<strong>Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of calcium and collagen I, II, and IX.</strong>
|
|
J. Biol. Chem. 276: 6083-6092, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11084047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11084047</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11084047" 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/10.1074/jbc.M009512200" 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="33" class="mim-anchor"></a>
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<a id="Unger2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Unger, S., Korkko, J., Krakow, D., Lachman, R. S., Rimoin, D. L., Cohn, D. H.
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<strong>Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal dysplasia congenita.</strong>
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Am. J. Med. Genet. 104: 140-146, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11746045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11746045</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11746045" 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.10062" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 01/19/2021
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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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Patricia A. Hartz - updated : 10/17/2013<br>Marla J. F. O'Neill - updated : 7/11/2012<br>George E. Tiller - updated : 11/12/2010<br>Victor A. McKusick - updated : 1/11/2005<br>Natalie E. Krasikov - updated : 3/30/2004<br>Victor A. McKusick - updated : 8/19/2003<br>Victor A. McKusick - updated : 12/30/2002<br>Victor A. McKusick - updated : 12/13/2002<br>Sonja A. Rasmussen - updated : 7/10/2002<br>Joanna S. Amberger - updated : 6/7/2002<br>Sonja A. Rasmussen - updated : 12/7/2001<br>Victor A. McKusick - updated : 9/20/2001<br>Victor A. McKusick - updated : 4/12/2001<br>Sonja A. Rasmussen - updated : 10/1/1999<br>Victor A. McKusick - updated : 2/18/1999<br>Victor A. McKusick - updated : 2/1/1999<br>Victor A. McKusick - updated : 1/20/1999<br>Victor A. McKusick - updated : 1/15/1999<br>Victor A. McKusick - updated : 4/18/1998<br>Victor A. McKusick - updated : 6/18/1997<br>Victor A. McKusick - updated : 3/27/1997
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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 : 1/18/1995
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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 : 01/19/2021
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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 : 11/01/2019<br>carol : 10/31/2019<br>carol : 12/06/2017<br>carol : 07/14/2016<br>alopez : 5/18/2015<br>alopez : 10/17/2013<br>alopez : 10/17/2013<br>alopez : 10/17/2013<br>alopez : 10/17/2013<br>alopez : 10/14/2013<br>carol : 4/18/2013<br>carol : 7/11/2012<br>wwang : 11/18/2010<br>terry : 11/12/2010<br>ckniffin : 10/16/2007<br>ckniffin : 10/15/2007<br>alopez : 1/28/2005<br>alopez : 1/28/2005<br>wwang : 1/18/2005<br>wwang : 1/14/2005<br>wwang : 1/12/2005<br>terry : 1/11/2005<br>carol : 10/8/2004<br>carol : 4/29/2004<br>carol : 4/7/2004<br>carol : 4/7/2004<br>terry : 3/30/2004<br>mgross : 8/21/2003<br>terry : 8/19/2003<br>carol : 1/9/2003<br>tkritzer : 1/6/2003<br>terry : 12/30/2002<br>terry : 12/30/2002<br>tkritzer : 12/18/2002<br>terry : 12/13/2002<br>carol : 7/10/2002<br>alopez : 6/10/2002<br>joanna : 6/7/2002<br>mcapotos : 12/17/2001<br>mcapotos : 12/7/2001<br>mcapotos : 9/27/2001<br>mcapotos : 9/25/2001<br>terry : 9/20/2001<br>mcapotos : 4/24/2001<br>mcapotos : 4/18/2001<br>terry : 4/12/2001<br>carol : 10/1/1999<br>mgross : 2/25/1999<br>mgross : 2/22/1999<br>terry : 2/18/1999<br>carol : 2/1/1999<br>carol : 2/1/1999<br>terry : 1/20/1999<br>carol : 1/20/1999<br>terry : 1/15/1999<br>carol : 4/18/1998<br>terry : 3/27/1998<br>jenny : 6/23/1997<br>mark : 6/18/1997<br>jenny : 3/27/1997<br>terry : 3/21/1997<br>jamie : 1/29/1997<br>mimadm : 9/23/1995<br>mark : 6/30/1995<br>carol : 1/18/1995
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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">
|
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<strong>*</strong> 600310
|
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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>
|
|
<span class="mim-font">
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|
|
CARTILAGE OLIGOMERIC MATRIX PROTEIN; COMP
|
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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-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
THROMBOSPONDIN V; THBS5
|
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</span>
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: COMP</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">
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<strong>SNOMEDCT:</strong> 22567005, 715673002;
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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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<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: 19p13.11
|
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|
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Genomic coordinates <span class="small">(GRCh38)</span> : 19:18,782,773-18,791,305 </span>
|
|
</em>
|
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</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<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>
|
|
<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>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
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</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
19p13.11
|
|
</span>
|
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</td>
|
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Carpal tunnel syndrome 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619161
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
|
</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, 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
132400
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
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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">
|
|
Pseudoachondroplasia
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
177170
|
|
</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
|
</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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<br />
|
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</div>
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<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
<span class="mim-text-font">
|
|
<p>COMP is a pentameric extracellular matrix protein that catalyzes the assembly of collagens and promotes formation of well-defined fibrils (Halasz et al., 2007). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
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|
|
<span class="mim-text-font">
|
|
<p>Cartilage oligomeric matrix protein is a 524-kD protein that is expressed at high levels in the territorial matrix of chondrocytes. The sequences of rat and bovine COMP indicate that it is a member of the thrombospondin gene family (Newton et al., 1994). </p><p>Maddox et al. (2000) reported that 5 identical COMP molecules associate via their N-terminal coiled-coil domains into a bouquet-like structure with 5 flexible arms. The flexible arms contain 4 EGF-like repeats, followed by 8 thrombospondin (see 188060) type 3 repeats, and a large C-terminal globular domain. The type 3 repeats are predicted to bind calcium. </p><p>Kleerekoper et al. (2002) stated that full-length human COMP contains 757 amino acids. </p><p>Halasz et al. (2007) stated that in young cartilage COMP is primarily identified close to chondrocytes, whereas in adult cartilage it is found in the interterritorial region. </p><p>Using immunohistochemical analysis, Agarwal et al. (2012) detected COMP expression in normal human skin. COMP localized in a continuous linear pattern mainly at the superficial papillary dermis, just below epidermal keratinocytes. Much lower expression was detected in reticular dermis. Quantitative real-time RT-PCR detected abundant COMP expression in extracts of separated dermis and in cultured primary dermal fibroblasts, but not in epidermal extracts or cultured HaCaT keratinocytes. Electron microscopy revealed that COMP localized subepidermally in clusters that overlapped with, but were not limited to, anchoring plaques. In skin, COMP expression partly colocalized with collagens XII (COL12A1; 120320) and XIV (COL14A1; 120324). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
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<span class="mim-text-font">
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|
<p>Thur et al. (2001) expressed recombinant wildtype rat COMP that showed structural and functional properties identical to COMP isolated from cartilage. The fragment encompassing the 8 type-3 repeats bound 14 calcium ions with moderate affinity and high cooperativity and presumably formed 1 large disulfide-bonded folding unit. A recombinant PSACH mutant COMP in which asp469 was deleted and a EDM mutant COMP in which asp361 was substituted by tyr (D361Y) were both secreted into the cell culture medium of human cells. The number of bound calcium ions was reduced. In addition to collagen I (see 120150) and II (see 120140), collagen IX normally binds to COMP with high affinity; the PSACH and EDM mutations reduced the binding of these 3 collagens and resulted in altered zinc dependence. These interactions may explain why EDM can also be caused by mutations in collagen IX genes (COL9A2, 120260 and COL9A3, 120270). </p><p>Using rotary shadowing electron microscopy and immobilized proteins, Holden et al. (2001) characterized the interaction between purified chick sternal cartilage type IX collagen (see COL9A1, 120210) and purified fetal bovine Comp or the isolated human COMP C-terminal domain. They identified a collagen-binding site between residues 579 and 595 of the C-terminal domain of COMP that bound each of 4 noncollagenous domains in collagen IX. </p><p>Using a yeast 2-hybrid screen, Liu et al. (2006) found that human COMP interacted with the extracellular metalloprotease Adamts7 (605009) in a rat brain cDNA library. The interaction was confirmed by protein pull-down and immunoprecipitation experiments. Domain analysis revealed that the C-terminal thrombospondin repeats of Adamts7 interacted with the EGF-like domain of COMP. Both full-length Adamts7 and the isolated catalytic domain (amino acids 217 to 468) of human ADAMTS7 digested COMP in a dose- and time-dependent manner. </p><p>Halasz et al. (2007) stated that pentameric bovine Comp binds via each C-terminal globule domain to 1 of 4 sites on collagens I (see 120150) and II (see 120140). They found that monomeric recombinant bovine Comp lacking the N-terminal coiled-coil domain showed weak fibril formation with collagens I and II. Fibril formation was much faster in the presence of purified pentameric Comp. Comp interacted primarily with free collagen I and II molecules, bringing several molecules to close proximity and promoting their assembly. Comp was not associated with mature fibrils and dissociates from the collagen molecules or their early assemblies. Halasz et al. (2007) concluded that COMP catalyzes fibril formation by promoting early association of collagen molecules, leading to increased rate of fibrillogenesis. </p><p>By characterizing mouse constructs expressed in human HEK293-EBNA cells, Agarwal et al. (2012) found that pentameric Comp bound collagens XII and XIV. In both cases, Comp bound to C-terminal collagenous domains of the collagens, but not to their large noncollagenous-3 domains. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Briggs et al. (1995) demonstrated that the COMP gene contains 19 exons. Exons 4-19, which encode the EGF-like (type II) repeats, calmodulin-like (type III) repeats (CLRs), and the C-terminal domain, correspond in sequence and intron location to the thrombospondin genes, whereas exons 1-3 are unique to COMP. They presented a table giving the gene structure of COMP in terms of exon size, intron location, and nucleotide sequence of the splice donor and splice acceptor regions of all exon/intron junctions. </p>
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</span>
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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>By Southern blot analysis of a somatic cell hybrid DNA panel and by isotopic in situ hybridization, Newton et al. (1994) mapped the human COMP gene to 19p13.1. Newton et al. (1994) mapped the murine Comp gene to the central region of mouse chromosome 8 by use of an interspecific backcross mapping panel. </p>
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</span>
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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>Evolution</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Newton et al. (1994) reported a phylogenetic analysis indicating that the COMP gene and a precursor of the thrombospondin-3 (188062) and thrombospondin-4 (600715) genes were produced by a gene duplication that occurred 750 million years ago. </p>
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</span>
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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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<span class="mim-text-font">
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<p><strong><em>Pseudoachondroplasia and Multiple Epiphyseal Dysplasia-1</em></strong></p><p>
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COMP was a candidate gene for the site of the mutation in both pseudoachondroplasia (PSACH; 177170) and one form of multiple epiphyseal dysplasia (EDM1; 132400) because both disorders mapped to 19p13.1-p12. Hecht et al. (1995) used single-strand conformation polymorphism (SSCP) analysis and nucleotide sequencing to identify COMP mutations in 8 familial and isolated PSACH cases. All mutations involved either a 1-bp change or a 3-bp deletion in the same exon. In 6 patients, 6 mutation events either deleted or changed well-conserved aspartic acid residues within the calcium-binding type-3 repeats (see 600310.0001 and 600310.0004). </p><p>In the process of determining the COMP genomic sequence, Briggs et al. (1995) identified a polymorphic (GAAA)12 repeat at the 3-prime end of an Alu element within intron 9. Using this marker for study of linkage in 2 large families previously used to establish linkage to chromosome 19 of PSACH/EDM1, they found 2 individuals, 1 from each family, who were not recombinant at the COMP marker. The 2 had been shown previously to be recombinant at flanking markers used to define the 800-kb PSACH/EDM1 interval. Briggs et al. (1995) also demonstrated specific mutations in the COMP gene in 2 patients with pseudoachondroplasia (600310.0006 and 600310.0018) and 1 patient with the Fairbank form of EDM (600310.0005). Thus, the allelic nature of these 2 disorders was established. </p><p>Susic et al. (1997) found heterozygosity for a 12-bp deletion in exon 10 of the COMP gene in a child with a mild form of pseudoachondroplasia. A child with the Fairbank type of multiple epiphyseal dysplasia was heterozygous for a cys371-to-ser amino acid substitution in the fourth CLR. These findings were thought to support the proposal that deletions and insertions within the calmodulin-like domain produce pseudoachondroplasia, whereas amino acid substitutions within this domain may produce either pseudoachondroplasia or EDM. </p><p>Briggs et al. (1998) reported identification of COMP mutations in an additional 14 families with PSACH or EDM phenotypes. Mutations predicted to result in single amino acid deletions or substitutions, all in the region of the COMP gene encoding the CLR elements, were identified in patients with moderate to severe PSACH (see, e.g., 600310.0004 and 600310.0018). They also identified within this domain a missense mutation that produced EDM of the Fairbank type. In 2 families, one with mild PSACH and the other with a form of EDM, they identified different substitutions for a residue in the C-terminal globular region of COMP. Both the clinical presentations of these 2 families and the identification of mutations in the COMP gene provided evidence of phenotypic overlap between PSACH and EDM. </p><p>In 12 patients with PSACH, Deere et al. (1998) identified 12 mutations in the COMP gene, including 10 novel mutations. The site of the mutations emphasized the importance of the calcium-binding domains and the globular domain to the function of COMP. </p><p>Deere et al. (1999) reported 9 novel mutations in COMP causing PSACH and EDM1. These included 4 mutations in exons 13C and 14 where no previous mutations had been identified, a case of PSACH resulting from an expansion of the 5 aspartates in exon 17B, and a PSACH family with somatic/germline mosaicism. </p><p>Ikegawa et al. (1998) screened the COMP gene in 15 patients with PSACH or EDM by direct sequencing of PCR products from genomic DNA. They identified 10 mutations involving conserved residues among the 8 CLRs of the gene product: 7 were missense mutations in exons 9, 10, 11, 13 or 14, and the other 3 resulted from deletion of 1 of the 5 GAC repeats in exon 13 (600310.0004). They found that the GAC repeats in the seventh CLR in exon 13 represent a hotspot for mutation and that mutations in the seventh calmodulin-like repeat produce severe PSACH phenotypes whereas mutations elsewhere in the gene exhibit mild PSACH or EDM phenotypes. They suggested that these genotype/phenotype correlations may facilitate molecular diagnosis and classification of PSACH and EDM, and provide insight into the relationship between structure and function of the COMP gene product. </p><p>Delot et al. (1999) stated that about one-third of patients with PSACH are heterozygous for deletion of 1 codon within a very short triplet repeat, (GAC)5, which encodes 5 consecutive aspartic acid residues within the calmodulin-like region of the COMP protein (600310.0004). Delot et al. (1999) identified 2 expansion mutations in this repeat: an EDM patient carrying a (GAC)6 allele (600310.0012), and a PSACH patient carrying a (GAC)7 allele (600310.0011). These were among the shortest disease-causing triplet repeat expansion mutations described to that time, and the first identified in a GAC repeat. A unique feature of this sequence was that expansion as well as shortening of the repeat could cause the same disease. In cartilage, both patients had the rough endoplasmic reticulum inclusions in chondrocytes. These inclusions were also present in tendon tissue and could be reproduced in cultured tendon cells, suggesting that the pathophysiology of the disease is similar in both cartilage and tendon. </p><p>Another example of disease production by expansion of a short trinucleotide repeat has been observed in the case of the polyadenylate-binding protein-2 gene (PABP2; 602279), which is mutant in oculopharyngeal muscular dystrophy (OPMD; 164300). In OPMD, the common (GCG)6 wildtype sequence was found to be expanded to pathologic (GCG)7-13 alleles.</p><p>Late-onset mild EDM is occasionally indistinguishable from common osteoarthritis (165720). Furthermore, a mutation in the C terminus of the COMP gene was reported by Briggs et al. (1998) as producing an individual of normal height with skeletal abnormalities that included early osteoarthritis. For these reasons, Mabuchi et al. (2001) hypothesized that osteoarthritis as a common disorder may be at the mild end of the phenotypic gradation produced by COMP mutations. They ascertained the sequences of the exons and exon-intron boundaries and identified 16 polymorphisms in the COMP gene. Using 6 polymorphisms spanning the entire COMP gene, they examined the association of this gene in Japanese patients with osteoarthritis of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between osteoarthritis and control groups, and there was no significant difference in haplotypes. </p><p>Mabuchi et al. (2003) reported the identification of 9 novel and 3 recurrent COMP mutations in PSACH and EDM patients. These included 2 novel types of mutations: a deletion spanning an exon-intron junction causing an exon deletion (600310.0015), and a frameshift mutation resulting in a truncation of the C-terminal domain (600310.0016). The remaining mutations, other than a novel exon 18 mutation, affected highly conserved aspartate or cysteine residues in the CLR region. Genotype-phenotype analysis revealed a correlation between the position and type of mutations and the severity of short stature. Mutations in the seventh CLR produced more severe short stature compared with mutations elsewhere in the CLRs and elsewhere in the COMP gene. Patients carrying mutations within the 5-aspartate repeat (amino acids 469-473) in the seventh CLR were extremely short (below -6 SD). Patients with deletion mutations were significantly shorter than those with substitution mutations. </p><p>Song et al. (2003) identified mutations in the COMP gene in 9 of 9 Korean patients with PSACH and in 3 of 5 Korean patients with EDM. Three of the 8 mutations identified were novel. </p><p>Jakkula et al. (2003) identified a mutation in the COMP gene (600310.0017) in patients presenting with muscular weakness, a moderate rise in creatine kinase and EDM beginning in the knee joints. They suggested that the clinical and radiographic overlap between collagen IX-EDM and COMP-EDM pointed to a common supramolecular complex pathogenesis. </p><p>Genetic diagnosis of the COMP-related skeletal dysplasias pseudoachondroplasia and multiple epiphyseal dysplasia is difficult because COMP mutations are scattered throughout the gene and 5 additional disease genes for multiple epiphyseal dysplasia exist. Mabuchi et al. (2004) presented evidence that plasma COMP levels are significantly decreased in patients with COMP mutations compared with controls (p less than 0.0001). In addition, plasma COMP levels were significantly decreased in EDM patients carrying mutations in COMP relative to those who lacked COMP mutations (p = 0.001). These results indicated that measuring the level of circulating COMP may be an easier, more rapid, and cost-efficient method for diagnosing PSACH and particularly for diagnosing EDM. </p><p><strong><em>Carpal Tunnel Syndrome 2</em></strong></p><p>
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In a large 5-generation family (family 1) with carpal tunnel syndrome mapping to chromosome 19p12 (CTS2; 619161), Li et al. (2020) sequenced the targeted locus and identified a heterozygous missense mutation in the COMP gene (V66E; 600310.0019) that segregated with disease. In a second family (family 2), in which affected individuals exhibited both CTS and EDM, whole-exome sequencing revealed heterozygosity for the R718W substitution in COMP (600310.0017), a known recurrent mutation associated with EDM1. Functional analysis revealed that secretion of the R718W mutant was reduced in both primary tendon cells and chondrocytes, whereas secretion of V66E was reduced only in tendon cells; the authors noted that this might account for the different phenotypes in the 2 families. </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>To study the role of COMP in vivo, Svensson et al. (2002) generated COMP-null mice and found that they showed no anatomic, histologic, or ultrastructural abnormalities associated with the pseudoachondroplasia (177170) or multiple epiphyseal dysplasia (132400) phenotypes. Northern blot and immunohistochemical analyses of cartilage indicated that the lack of COMP was not compensated for by any other member of the thrombospondin family. Svensson et al. (2002) reported that the phenotype in PSACH and EDM is caused not by the reduced amount of COMP but by some other mechanism, such as folding defects or extracellular assembly abnormalities due to dysfunctional mutated COMP. </p><p>PSACH and EDM patients often have a mild myopathy characterized by mildly increased plasma creatine kinase levels, a variation in myofiber size and/or small atrophic fibers. Pirog et al. (2010) studied skeletal muscle, tendon, and ligament in a mouse model of mild PSACH harboring a T585M mutation. T585M-mutant mice exhibited a progressive muscle weakness associated with an increased number of muscle fibers with central nuclei at the perimysium and at the myotendinous junction. Collagen fibril diameters in the mutant tendons and ligaments were thicker, and tendons became more lax in cyclic strain tests. Pirog et al. (2010) hypothesized that the myopathy in PSACH-EDM may originate from underlying tendon and ligament pathology that may be a direct result of abnormalities in collagen fibril architecture. </p><p>Using homologous recombination, Suleman et al. (2012) generated a knock-in mouse model carrying the common D469del mutation in the COMP gene (600310.0004), which is found in approximately one-third of patients with PSACH. In contrast to the human PSACH phenotype, which is a dominant disease, both copies of the mutant allele were required for the mice to develop a quantifiable chondrodysplasia phenotype. Mutant animals were normal at birth but grew slower than their wildtype littermates and developed short-limb dwarfism. In growth plates of mutant mice, chondrocyte columns were reduced in number and poorly organized, and mutant COMP was retained within the endoplasmic reticulum of cells. Chondrocyte proliferation was reduced and apoptosis was both increased and spatially dysregulated. Unlike earlier studies, Suleman et al. (2012) observed no evidence of an unfolded protein response in this mouse model of PSACH. In contrast, microarray analysis identified expression changes in groups of genes implicated in oxidative stress, cell cycle regulation, and apoptosis, consistent with the chondrocyte pathology. Suleman et al. (2012) suggested that a novel form of chondrocyte stress triggered by the expression of mutant COMP is central to the pathogenesis of PSACH. </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>19 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 PSEUDOACHONDROPLASIA</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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COMP, ASP472TYR
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<br />
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SNP: rs137852650,
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ClinVar: RCV000009761
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with pseudoachondroplasia (PSACH; 177170), Hecht et al. (1995) demonstrated a G-to-T transversion at nucleotide 1439 of the COMP gene, resulting in an asp472-to-tyr amino acid substitution. The single nucleotide substitution occurred in 1 of the 5 GAC repeats, converting GAC to TAC. </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 PSEUDOACHONDROPLASIA</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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COMP, CYS468TYR
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<br />
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SNP: rs137852651,
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ClinVar: RCV000009762, RCV002247283, RCV002512949
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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 isolated case of pseudoachondroplasia (PSACH; 177170), Hecht et al. (1995) observed a G-to-A transition at nucleotide 1428 of the COMP gene, leading to a cys468-to-tyr amino acid substitution. </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 PSEUDOACHONDROPLASIA</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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COMP, 3-BP DEL, 459TCA
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<br />
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SNP: rs2145900868,
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ClinVar: RCV000009763
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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 isolated case of pseudoachondroplasia (PSACH; 177170), Hecht et al. (1995) observed deletion of nucleotides 1400-1402 (TCA) of the COMP gene, resulting in deletion of serine-459. </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 PSEUDOACHONDROPLASIA</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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COMP, 3-BP DEL, 1430GAC
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<br />
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SNP: rs193922900,
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ClinVar: RCV000033880, RCV000486037, RCV001332185
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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 5 unrelated patients with pseudoachondroplasia (PSACH; 177170), including 1 from a family originally reported by Hall and Dorst (1969), Hecht et al. (1995) identified a 3-bp deletion removing 1 of the 5 GAC repeat sequences at cDNA nucleotides 1430-1445 of the COMP gene. This resulted in the loss of an aspartate residue in a calcium-binding site. </p><p>In 2 sporadic patients and affected members of 5 families with PSACH, Briggs et al. (1998) identified heterozygosity for a 3-bp deletion (delGAC 1430-1444) in exon 13 of the COMP gene, resulting in removal of 1 of 5 consecutive aspartic acid residues corresponding to codons 469 to 473 within the seventh calmodulin-like repeat. The authors noted that the repeated nature of the GAC sequence did not allow precise determination of the codon that was deleted in the patients. </p><p>In 3 sporadic patients with PSACH, Ikegawa et al. (1998) identified heterozygosity for a 3-bp deletion within the (GAC)5 trinucleotide repeat region in exon 13. Ikegawa et al. (1998) noted that, like the previously reported patients with this mutation, the phenotype was severe in all 3 patients, their adult heights being less than 110 cm. </p><p>Briggs and Chapman (2002) reviewed mutations in the COMP gene resulting in PSACH and, using nucleotide numbering from the start site of translation, designated this nucleotide change as 1405-1419 delGAC and the corresponding protein change as delD(469-473). This mutation is thought to account for approximately one-third of PSACH patients. It is a contraction of a short trinucleotide repeat; expansion of this repeat to (GAC)6 and (GAC)7 are represented by 2 other entries, 600310.0012 and 600310.0011, respectively (Delot et al., 1999). </p><p><strong><em>Mutation Function</em></strong></p><p>
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Deletion of 1 of the 5 asp codons in the type 3 calcium-binding domain of COMP essentially deletes the single asp470 spacer between calcium-binding loops 10 and 11. Kleerekoper et al. (2002) created recombinant mutant COMP proteins that carried a deletion of asp470, mimicking the deletion found in PSACH patients, and found that this deletion decreased the calcium binding capacity of COMP. Calcium binding by this domain is required to nucleate folding. The authors predicted that persistence of the unstructured state of the mutated calcium-binding domain would lead to retention of COMP in the rough endoplasmic reticulum of differentiated PSACH and EDM1 chondrocytes. </p><p>Dinser et al. (2002) developed a cell culture model of pseudoachondroplasia by expressing mutant COMP (D469del) in bovine primary chondrocytes. They showed that mutant COMP exerts its deleterious effects through both intra- and extracellular pathogenic pathways. Overexpression of mutant COMP led to a dose-dependent decrease in cellular viability. The secretion of mutant COMP was markedly delayed, presumably due to a prolonged association with chaperones in the endoplasmic reticulum. The extracellular matrix lacked organized collagen fibers and showed amorphous aggregates formed by mutant COMP. Thus, pseudoachondroplasia appeared to be an endoplasmic reticulum storage disease, most likely caused by improper folding of mutant COMP. The growth failure of patients with pseudoachondroplasia may be explained by an increased cell death of growth-plate chondrocytes. Dominant interference of the mutant protein with collagen fiber assembly could contribute to the observed failure of the extracellular matrix of cartilage and tendons. </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, 1, SEVERE</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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COMP, ASP342TYR
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<br />
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SNP: rs137852652,
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ClinVar: RCV000009765
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with a severe form of multiple epiphyseal dysplasia-1 (EDM1; 132400), Briggs et al. (1995) identified a de novo heterozygous mutation in the COMP gene, resulting in an asp342-to-tyr (D342Y) substitution in a conserved residue in the third calmodulin-like repeat. The mutation created an RsaI restriction endonuclease cleavage site. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0006 PSEUDOACHONDROPLASIA</strong>
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|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
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<span class="mim-text-font">
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COMP, CYS328ARG
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<br />
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SNP: rs137852653,
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|
|
ClinVar: RCV000009766
|
|
|
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|
|
</span>
|
|
</div>
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|
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<div>
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<span class="mim-text-font">
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|
<p>In an affected individual from a family with a moderately severe form of pseudoachondroplasia (PSACH; 177170), Briggs et al. (1995) found heterozygosity for a point mutation that predicted substitution of arginine for the cysteine at residue 328 (cys328-to-arg; C328R). The mutation altered a conserved residue in the second calmodulin-like repeat of COMP. The change created a new cleavage site which was identified in genomic DNA in all 4 affected members of the family but in no unaffected individuals. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-text-font">
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<strong>.0007 MOVED TO 600310.0004</strong>
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</span>
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</h4>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0008 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1, MILD</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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COMP, ASN523LYS
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<br />
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SNP: rs137852654,
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|
|
ClinVar: RCV000009767, RCV001851774, RCV002054430
|
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|
|
</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In affected members of a South African family with a mild form of multiple epiphyseal dysplasia-1 (EDM1; 132400), Ballo et al. (1997) identified a heterozygous 1594C-G transversion in the COMP gene, resulting in an asn523-to-lys (N523K) substitution, which altered a residue at the C-terminal end of the calmodulin-like region of the protein. There were affected individuals in 3 generations. Radiologic findings in a mother and son included flattening and irregularity of femoral heads and unevenness of the intraarticular aspects of the distal end of the femurs and proximal end of the tibias. The lateral femoral condyles were hypoplastic. The endplates of the vertebral bodies showed mild sclerosis and irregularity, but there was no significant flattening. Ballo et al. (1997) stated that the identification of this mutation demonstrates that the spectrum of manifestations from mild EDM through pseudoachondroplasia can all be produced by structural mutations in COMP. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1, SEVERE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
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|
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|
COMP, ASN453SER
|
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|
<br />
|
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|
|
SNP: rs28936668,
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|
|
ClinVar: RCV000009768
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|
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|
|
|
</span>
|
|
</div>
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|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (family R94-344) with a severe form of multiple epiphyseal dysplasia-1 (EDM1; 132400), Briggs et al. (1998) found a 1383A-G transition in exon 13 of the COMP gene which resulted in an asn453-to-ser (N453S) amino acid substitution located in the calmodulin-like domain 7. The proband was first seen at the age of 15 years when she was short of stature (height 144 cm) and complained of pain in the knees. The hands were normal. Radiographs showed normal hands and hips, but the tibial epiphyses were irregular, with a squared aspect. Her affected sister was also short of stature and had involvement of the knees and hips. The femoral head was small and irregular, but the severity of the deformities was somewhat less striking than those of other cases of EDM Fairbank. The affected father had knee involvement but the hips were unaffected. The affected grandmother had severe hip dysplasia that required surgical replacement of the femoral head. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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|
</div>
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|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 PSEUDOACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COMP, ASP473GLY
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|
|
|
<br />
|
|
|
|
SNP: rs28936669,
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|
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|
|
|
|
|
ClinVar: RCV000009769
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sporadic case of pseudoachondroplasia (PSACH; 177170), Ikegawa et al. (1998) described an interstitial deletion in 11q. In a subsequent sequence analysis, (Ikegawa, 1998) identified a 1418A-G transition in the COMP gene, resulting in an asp473-to-gly (D473G) amino acid substitution. The deletion was apparently fortuitous; since the mutation was de novo (absent in the normal parents) and substituted a highly conserved aspartic acid residue, it was presumably the cause of the disorder. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
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|
|
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</div>
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|
|
|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 PSEUDOACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COMP, 6-BP INS, (GAC)7
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000009770, RCV004730840
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sporadic case of pseudoachondroplasia (PSACH; 177170), Delot et al. (1999) identified an expansion of the short trinucleotide repeat, (GAC)5, located at cDNA dinucleotides 1430 to 1444 of the COMP gene. The patient was found to be heterozygous for a (GAC)7 allele. The diagnosis of typical PSACH had been established at 3 years of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COMP, 3-BP INS, (GAC)6
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193922900,
|
|
|
|
|
|
|
|
ClinVar: RCV000009771, RCV000033881, RCV001090556, RCV002054431
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with multiple epiphyseal dysplasia-1 (EDM1; 132400) from a family with autosomal dominant inheritance, Delot et al. (1999) found an expansion of the short (GAC)5 repeat; the patient was heterozygous for a (GAC)6 allele. The diagnosis of EDM1 had been established at the age of 13 years; she was noted to have short stature and radiographic abnormalities confined to the epiphyses of the long bones. The affected mother had undergone surgery to replace the left and right hips at 35 and 37 years of age, respectively. The adult height of the proband was 153 cm and her affected mother was 160 cm tall. By comparison, 2 unaffected females in the family were 168 and 173 cm tall. A brother was more severely affected and underwent bilateral osteotomies at 16 years of age for genu varum. The proband underwent hip replacement surgery at age 34, at which time cartilage and tendon from the femoral head were obtained. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 PSEUDOACHONDROPLASIA, SEVERE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COMP, GLY719ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852655,
|
|
|
|
|
|
|
|
ClinVar: RCV000009772, RCV000033890, RCV002223755, RCV003989283
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mabuchi et al. (2001) reported a case with severe pseudoachondroplasia (PSACH; 177170), including marked short stature and deformities of the spine and extremities. The patient had a G-to-A transition (GGT-GAT) at nucleotide 2156 in exon 18 of the COMP gene. The mutation was predicted to cause a gly719-to-asp (G719D) substitution in the C-terminal globular domain and was the first case with a severe pseudoachondroplasia phenotype with a mutation outside the seventh calmodulin-like repeat. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 PSEUDOACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COMP, CYS348ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852656,
|
|
|
|
|
|
|
|
ClinVar: RCV000009773, RCV003555993
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Unger et al. (2001) reported a child with double heterozygosity for pseudoachondroplasia (PSACH; 177170), resulting from a cys348-to-arg mutation in the COMP gene, and spondyloepiphyseal dysplasia congenita (183900), resulting from a mutation in the COL2A1 gene (120140.0035). The child inherited pseudoachondroplasia from his mother and spondyloepiphyseal dysplasia congenita from his father. He had clinical and radiographic findings that were more severe than those in either disorder alone. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 PSEUDOACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COMP, 533-BP DEL, EX9
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2145902395,
|
|
|
|
|
|
|
|
ClinVar: RCV000009774
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mabuchi et al. (2003) described a 533-bp deletion extending from exon 9 to intron 9 of the COMP gene in a patient with severe pseudoachondroplasia (PSACH; 177170); his height was below -8 SD and his joint involvement was multiple and severe. The aberrant allele would significantly affect the conformation of the COMP protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1, MILD</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COMP, 1-BP INS, 2223C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs869320730,
|
|
|
|
|
|
|
|
ClinVar: RCV000009775
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (MED5) with a mild form of multiple epiphyseal dysplasia-1 (EDM1; 132400), Mabuchi et al. (2003) described a cytosine inserted between nucleotides 2223 and 2224 in the C-terminal part of the COMP gene. The insertion changed codon 742 from AAT (asn) to CAA (gln) with a frameshift that changed codon 743 from GAC (asp) to TGA (ter); the mutation was symbolized Asn742fsTer743. Asn742, the first affected amino acid, is the predicted site for N-linked glycosylation. The insertion caused premature termination of the codon and a truncated COMP protein. The mutation was located immediately following cys741. Although the frameshift mutation was predicted to produce a considerably truncated protein (15 amino acids shorter), the phenotypic effect was mild. Members of the family showed involvement of the hip and knee joints, but their stature was normal. Therefore, the sequence following cys741 may have little impact for COMP function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 EPIPHYSEAL DYSPLASIA, MULTIPLE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
CARPAL TUNNEL SYNDROME 2, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COMP, ARG718TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28936368,
|
|
|
|
|
|
gnomAD: rs28936368,
|
|
|
|
|
|
ClinVar: RCV000009776, RCV001268837, RCV001289465, RCV002054432
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Multiple Epiphyseal Dysplasia 1</em></strong></p><p>
|
|
In a patient with a severe form of multiple epiphyseal dysplasia-1 (EDM1; 132400), Mabuchi et al. (2003) identified a 2152C-T transition in exon 18 of the COMP gene, resulting in an arg718-to-trp (R718W) substitution. </p><p>Jakkula et al. (2003) identified the same mutation in patients with EDM1 who had muscle weakness, moderate creatine kinase elevation, and EDM beginning with the knee joints. No disease-causing mutations were detected in collagen IX genes. </p><p><strong><em>Carpal Tunnel Syndrome 2</em></strong></p><p>
|
|
In affected members of a large 4-generation family (family 2) with carpal tunnel syndrome (CTS2; 619161) as well as signs of EDM, Li et al. (2020) identified heterozygosity for the c.2152C-T transition (c.2152C-T, NM_000095.3) in the COMP gene resulting in the R718W mutation. The mutation segregated fully with disease in the family and was not found in human genome variation databases. Functional analysis showed that secretion of the R718W mutant was reduced in both primary tendon cells and chondrocytes compared to wildtype COMP. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 PSEUDOACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COMP, 3-BP DEL, 1139GAC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1198060288,
|
|
|
|
|
|
gnomAD: rs1198060288,
|
|
|
|
|
|
ClinVar: RCV001901762, RCV002259406, RCV002290796
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
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<p>In an individual with moderately severe pseudoachondroplasia (PSACH; 177170), Briggs et al. (1995) identified heterozygosity for a 3-bp deletion in exon 10 of the COMP gene, which eliminated a codon for an aspartic acid residue from the (GAC)3 repeat within the fourth calmodulin-like repeat. Due to the repeated sequence of nucleotides 1139-1147, it was not possible to determine which 3 nucleotides were deleted and, hence, which aspartic acid codon (372-374) was eliminated. The occurrence of the deletion in a series of direct repeats suggested that the mutation resulted from slipped mispairing during DNA replication. </p><p>In a patient with typical PSACH, Briggs et al. (1998) identified heterozygosity for a 3-bp deletion (delGAC 1139-1147) in the COMP gene. Chondrocytes from the patient showed the characteristic lamellar inclusions of the rough endoplasmic reticulum observed in PSACH. </p><p>Briggs and Chapman (2002) reviewed mutations in the COMP gene resulting in PSACH and, using nucleotide numbering from the start site of translation, designated this nucleotide change as 1114-1122 delGAC and the corresponding protein change as delD(372-374). </p>
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</span>
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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>.0019 CARPAL TUNNEL SYNDROME 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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COMP, VAL66GLU
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<br />
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SNP: rs2055205599,
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ClinVar: RCV001289466
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</span>
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</div>
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<span class="mim-text-font">
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<p>In affected members of a large 5-generation family (family 1) with carpal tunnel syndrome mapping to chromosome 19p12 (CTS2; 619161), Li et al. (2020) identified heterozygosity for a c.197T-A transversion (c.197T-A, NM_000095.3) in exon 3 of the COMP gene, resulting in a val66-to-glu (V66E) substitution within the N-terminal homopentamer-forming coiled-coil domain. The mutation segregated fully with disease in the family and was not found in human genome variation databases. Functional studies showed that secretion of the V66E mutant was reduced in primary tendon cells, whereas secretion in chondrocytes was as efficient as wildtype COMP. Fractionation analysis revealed that the V66E substitution disrupts COMP pentamerization, and the mutant COMP did not colocalize with type I collagen (see 120150) in the extracellular matrix (ECM), suggesting that proper oligomerization is important for sufficient COMP secretion in primary tendon cells and integration into the ECM protein complex. Coexpression of wildtype and mutant COMP in primary tendon cells showed that the V66E mutant impaired the secretion of wildtype COMP, indicating a dominant-negative effect. In a knockin mouse model of a V65E Comp mutation, equivalent to the human V66E mutation, the authors observed reduced ability to repair tendon damage compared to wildtype or Comp -/- mice, also consistent with a dominant-negative effect. Ultrastructural and immunohistochemical analysis of patient tendon cells showed evidence of increased endoplasmic reticulum stress and tendon/ligament cell death, associated with inflammatory cells and fibrosis, which the authors noted might further impair ECM architecture. </p>
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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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<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 />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Agarwal, P., Zwolanek, D., Keene, D. R., Schulz, J.-N., Blumbach, K., Heinegard, D., Zaucke, F., Paulsson, M., Krieg, T., Koch, M., Eckes, B.
|
|
<strong>Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure.</strong>
|
|
J. Biol. Chem. 287: 22549-22559, 2012.
|
|
|
|
|
|
[PubMed: 22573329]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M111.335935]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ballo, R., Briggs, M. D., Cohn, D. H., Knowlton, R. G., Beighton, P. H., Ramesar, R. S.
|
|
<strong>Multiple epiphyseal dysplasia, Ribbing type: a novel point mutation in the COMP gene in a South African family.</strong>
|
|
Am. J. Med. Genet. 68: 396-400, 1997. Note: Erratum: Am. J. Med. Genet. 71: 494 only, 1997.
|
|
|
|
|
|
[PubMed: 9021009]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Briggs, M. D., Chapman, K. L.
|
|
<strong>Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review, molecular interactions, and genotype to phenotype correlations.</strong>
|
|
Hum. Mutat. 19: 465-478, 2002.
|
|
|
|
|
|
[PubMed: 11968079]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10066]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Briggs, M. D., Hoffman, S. M. G., King, L. M., Olsen, A. S., Mohrenweiser, H., Leroy, J. G., Mortier, G. R., Rimoin, D. L., Lachman, R. S., Gaines, E. S., Cekleniak, J. A., Knowlton, R. G., Cohn, D. H.
|
|
<strong>Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.</strong>
|
|
Nature Genet. 10: 330-336, 1995.
|
|
|
|
|
|
[PubMed: 7670472]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0795-330]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Briggs, M. D., Mortier, G. R., Cole, W. G., King, L. M., Golik, S. S., Bonaventure, J., Nuytinck, L., De Paepe, A., Leroy, J. G., Biesecker, L., Lipson, M., Wilcox, W. R., Lachman, R. S., Rimoin, D. L., Knowlton, R. G., Cohn, D. H.
|
|
<strong>Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.</strong>
|
|
Am. J. Hum. Genet. 62: 311-319, 1998.
|
|
|
|
|
|
[PubMed: 9463320]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/301713]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Deere, M., Sanford, T., Ferguson, H. L., Daniels, K., Hecht, J. T.
|
|
<strong>Identification of twelve mutations in cartilage oligomeric matrix protein (COMP) in patients with pseudoachondroplasia.</strong>
|
|
Am. J. Med. Genet. 80: 510-513, 1998.
|
|
|
|
|
|
[PubMed: 9880218]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19981228)80:5<510::aid-ajmg14>3.0.co;2-f]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Deere, M., Sanford, T., Francomano, C. A., Daniels, K., Hecht, J. T.
|
|
<strong>Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
Am. J. Med. Genet. 85: 486-490, 1999.
|
|
|
|
|
|
[PubMed: 10405447]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19990827)85:5<486::aid-ajmg10>3.0.co;2-o]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Delot, E., King, L. M., Briggs, M. D., Wilcox, W. R., Cohn, D. H.
|
|
<strong>Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene.</strong>
|
|
Hum. Molec. Genet. 8: 123-128, 1999.
|
|
|
|
|
|
[PubMed: 9887340]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/8.1.123]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dinser, R., Zaucke, F., Kreppel, F., Hultenby, K., Kochanek, S., Paulsson, M., Maurer, P.
|
|
<strong>Pseudoachondroplasia is caused through both intra- and extracellular pathogenic pathways.</strong>
|
|
J. Clin. Invest. 110: 505-513, 2002.
|
|
|
|
|
|
[PubMed: 12189245]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI14386]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Halasz, K., Kassner, A., Morgelin, M., Heinegard, D.
|
|
<strong>COMP acts as a catalyst in collagen fibrillogenesis.</strong>
|
|
J. Biol. Chem. 282: 31166-31173, 2007.
|
|
|
|
|
|
[PubMed: 17716974]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M705735200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, J. G., Dorst, J. P.
|
|
<strong>Pseudoachondroplastic SED, recessive Maroteaux-Lamy type.</strong>
|
|
Birth Defects Orig. Art. Ser. V(4): 254-259, 1969.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hecht, J. T., Nelson, L. D., Crowder, E., Wang, Y., Elder, F. F. B., Harrison, W. R., Francomano, C. A., Prange, C. K., Lennon, G. G., Deere, M., Lawler, J.
|
|
<strong>Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.</strong>
|
|
Nature Genet. 10: 325-329, 1995.
|
|
|
|
|
|
[PubMed: 7670471]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0795-325]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holden, P., Meadows, R. S., Chapman, K. L., Grant, M. E., Kadler, K. E., Briggs, M. D.
|
|
<strong>Cartilage oligomeric matrix protein interacts with type IX collagen, and disruptions to these interactions identify a pathogenetic mechanism in a bone dysplasia family.</strong>
|
|
J. Biol. Chem. 276: 6046-6055, 2001.
|
|
|
|
|
|
[PubMed: 11087755]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M009507200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ikegawa, S., Ohashi, H., Hosoda, F., Fukushima, Y., Ohki, M., Nakamura, Y.
|
|
<strong>Pseudoachondroplasia with de novo deletion [del(11)(q21q22.2)].</strong>
|
|
Am. J. Med. Genet. 77: 356-359, 1998.
|
|
|
|
|
|
[PubMed: 9632164]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19980605)77:5<356::aid-ajmg3>3.0.co;2-l]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ikegawa, S., Ohashi, H., Nishimura, G., Kim, K. C., Sannohe, A., Kimizuka, M., Fukushima, Y., Nagai, T., Nakamura, Y.
|
|
<strong>Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
Hum. Genet. 103: 633-638, 1998.
|
|
|
|
|
|
[PubMed: 9921895]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050883]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ikegawa, S.
|
|
<strong>Personal Communication.</strong>
|
|
Tokyo, Japan 11/30/1998.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jakkula, E., Lohiniva, J., Capone, A., Bonafe, L., Marti, M., Schuster, V., Giedion, A., Eich, G., Boltshauser, E., Ala-Kokko, L., Superti-Furga, A.
|
|
<strong>A recurrent R718W mutation in COMP results in multiple epiphyseal dysplasia with mild myopathy: clinical and pathogenetic overlap with collagen IX mutations.</strong>
|
|
J. Med. Genet. 40: 942-948, 2003.
|
|
|
|
|
|
[PubMed: 14684695]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.40.12.942]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kleerekoper, Q., Hecht, J. T., Putkey, J. A.
|
|
<strong>Disease-causing mutations in cartilage oligomeric matrix protein cause an unstructured Ca(2+) binding domain.</strong>
|
|
J. Biol. Chem. 277: 10581-10589, 2002.
|
|
|
|
|
|
[PubMed: 11782471]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M109944200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, C., Wang, N., Schaffer, A. A., Liu, X., Zhao, Z., Elliott, G., Garrett, L., Choi, N. T., Wang, Y., Wang, Y., Wang, C., Wang, J., Chan, D., Su, P., Cui, S., Yang, Y., Gao, B.
|
|
<strong>Mutations in COMP cause familial carpal tunnel syndrome.</strong>
|
|
Nature Commun. 11: 3642, 2020. Note: Electronic Article. Erratum: Nature Commun. 11: 3931, 2020.
|
|
|
|
|
|
[PubMed: 32686688]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41467-020-17378-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liu, C., Kong, W., Ilalov, K., Yu, S., Xu, K., Prazak, L., Fajardo, M., Sehgal, B., Di Cesare, P. E.
|
|
<strong>ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein.</strong>
|
|
FASEB J. 20: 988-990, 2006.
|
|
|
|
|
|
[PubMed: 16585064]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1096/fj.05-3877fje]
|
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|
|
|
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</p>
|
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</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
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Mabuchi, A., Haga, N., Ikeda, T., Manabe, N., Ohashi, H., Takatori, Y., Nakamura, K., Ikegawa, S.
|
|
<strong>Novel mutation in exon 18 of the cartilage oligomeric matrix protein gene causes a severe pseudoachondroplasia.</strong>
|
|
Am. J. Med. Genet. 104: 135-139, 2001.
|
|
|
|
|
|
[PubMed: 11746044]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.10067]
|
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</p>
|
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</li>
|
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|
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<li>
|
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<p class="mim-text-font">
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Mabuchi, A., Ikeda, T., Fukuda, A., Koshizuka, Y., Hiraoka, H., Miyoshi, K., Haga, N., Kawaguchi, H., Kawakami, A., Yamamoto, S., Takatori, Y., Nakamura, K., Ikegawa, S.
|
|
<strong>Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints.</strong>
|
|
J. Hum. Genet. 46: 456-462, 2001.
|
|
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|
|
|
[PubMed: 11501943]
|
|
|
|
|
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[Full Text: https://doi.org/10.1007/s100380170045]
|
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|
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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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Mabuchi, A., Manabe, N., Haga, N., Kitoh, H., Ikeda, T., Kawaji, H., Tamai, K., Hamada, J., Nakamura, S., Brunetti-Pierri, N., Kimizuka, M., Takatori, Y., Nakamura, K., Nishimura, G., Ohashi, H., Ikegawa, S.
|
|
<strong>Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
Hum. Genet. 112: 84-90, 2003.
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[PubMed: 12483304]
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[Full Text: https://doi.org/10.1007/s00439-002-0845-9]
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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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Mabuchi, A., Momohara, S., Ohashi, H., Takatori, Y., Haga, N., Nishimura, G., Ikegawa, S.
|
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<strong>Circulating COMP is decreased in pseudoachondroplasia and multiple epiphyseal dysplasia patients carrying COMP mutations.</strong>
|
|
Am. J. Med. Genet. 129A: 35-38, 2004.
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[PubMed: 15266613]
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[Full Text: https://doi.org/10.1002/ajmg.a.30164]
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</p>
|
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</li>
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|
|
<li>
|
|
<p class="mim-text-font">
|
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Maddox, B. K., Mokashi, A., Keene, D. R., Bachinger, H. P.
|
|
<strong>A cartilage oligomeric matrix protein mutation associated with pseudoachondroplasia changes the structural and functional properties of the type 3 domain.</strong>
|
|
J. Biol. Chem. 275: 11412-11417, 2000.
|
|
|
|
|
|
[PubMed: 10753957]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.275.15.11412]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
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Newton, G., Weremowicz, S., Morton, C. C., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Lawler, J.
|
|
<strong>Characterization of human and mouse cartilage oligomeric matrix protein.</strong>
|
|
Genomics 24: 435-439, 1994.
|
|
|
|
|
|
[PubMed: 7713493]
|
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[Full Text: https://doi.org/10.1006/geno.1994.1649]
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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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Pirog, K. A., Jaka, O., Katakura, Y., Meadows, R. S., Kadler, K. E., Boot-Handford, R. P., Briggs, M. D.
|
|
<strong>A mouse model offers novel insights into the myopathy and tendinopathy often associated with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
Hum. Molec. Genet. 19: 52-64, 2010.
|
|
|
|
|
|
[PubMed: 19808781]
|
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|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp466]
|
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|
|
|
|
</p>
|
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</li>
|
|
|
|
<li>
|
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|
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Song, H.-R., Lee, K.-S., Li, Q.-W., Koo, S. K., Jung, S.-C.
|
|
<strong>Identification of cartilage oligomeric matrix protein (COMP) gene mutations in patients with pseudoachondroplasia and multiple epiphyseal dysplasia.</strong>
|
|
J. Hum. Genet. 48: 222-225, 2003.
|
|
|
|
|
|
[PubMed: 12768438]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-003-0013-7]
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|
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Suleman, F., Gualeni, B., Gregson, H. J., Leighton, M. P., Pirog, K. A., Edwards, S., Holden, P., Boot-Handford, R. P., Briggs, M. D.
|
|
<strong>A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia.</strong>
|
|
Hum. Mutat. 33: 218-231, 2012.
|
|
|
|
|
|
[PubMed: 22006726]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.21631]
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|
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Susic, S., McGrory, J., Ahier, J., Cole, W. G.
|
|
<strong>Multiple epiphyseal dysplasia and pseudoachondroplasia due to novel mutations in the calmodulin-like repeats of cartilage oligomeric matrix protein.</strong>
|
|
Clin. Genet. 51: 219-224, 1997.
|
|
|
|
|
|
[PubMed: 9184241]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1997.tb02458.x]
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</p>
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</li>
|
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Svensson, L., Aszodi, A., Heinegard, D., Hunziker, E. B., Reinholt, F. P., Fassler, R., Oldberg, A.
|
|
<strong>Cartilage oligomeric matrix protein-deficient mice have normal skeletal development.</strong>
|
|
Molec. Cell. Biol. 22: 4366-4371, 2002.
|
|
|
|
|
|
[PubMed: 12024046]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.22.12.4366-4371.2002]
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</p>
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</li>
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<li>
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Thur, J., Rosenberg, K., Nitsche, D. P., Pihlajamaa, T., Ala-Kokko, L., Heinegard, D., Paulsson, M., Maurer, P.
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|
<strong>Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of calcium and collagen I, II, and IX.</strong>
|
|
J. Biol. Chem. 276: 6083-6092, 2001.
|
|
|
|
|
|
[PubMed: 11084047]
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[Full Text: https://doi.org/10.1074/jbc.M009512200]
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Unger, S., Korkko, J., Krakow, D., Lachman, R. S., Rimoin, D. L., Cohn, D. H.
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<strong>Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal dysplasia congenita.</strong>
|
|
Am. J. Med. Genet. 104: 140-146, 2001.
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[PubMed: 11746045]
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[Full Text: https://doi.org/10.1002/ajmg.10062]
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