4761 lines
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Entry
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- *131195 - ENDOGLIN; ENG
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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">*131195</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/131195">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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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div 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 style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="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=ENSG00000106991;t=ENST00000373203" 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=2022" 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=131195" 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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<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=ENSG00000106991;t=ENST00000373203" 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_000118,NM_001114753,NM_001278138,NM_001406715" 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_001114753" 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=131195" 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=00565&isoform_id=00565_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/ENG" 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/182091,402207,3041681,3201589,3452261,4557555,15679936,30582583,62897649,114731557,119608108,119608109,119608110,158261801,168693647,194379568,194390342,221043488,366091022,497240517,2240436661" 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/P17813" 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=2022" 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=ENSG00000106991;t=ENST00000373203" 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=ENG" 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=ENG" 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+2022" 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/ENG" 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:2022" 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/2022" 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=chr9&hgg_gene=ENST00000373203.9&hgg_start=127815016&hgg_end=127854658&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/gene-dosage/HGNC:3349" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3349" 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/eng" 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=131195[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=131195[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/ENG/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/ENSG00000106991" 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=ENG" 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=ENG" 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=ENG" 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="http://arup.utah.edu/database/HHT" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ENG&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/PA27785" 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:3349" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:95392" 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/ENG#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:95392" 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/2022/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=2022" 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-170530-1" 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="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:131195" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=ENG&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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131195
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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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ENDOGLIN; ENG
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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CD105
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ENG" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ENG</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/9/525?start=-3&limit=10&highlight=525">9q34.11</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:127815016-127854658&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'})">9:127,815,016-127,854,658</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
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Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
|
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|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/9/525?start=-3&limit=10&highlight=525">
|
|
9q34.11
|
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</a>
|
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</span>
|
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</td>
|
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|
|
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<td>
|
|
<span class="mim-font">
|
|
Telangiectasia, hereditary hemorrhagic, type 1
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/187300"> 187300 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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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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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/131195" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<p>Endoglin (ENG), also called CD105, is a homodimeric membrane glycoprotein primarily associated with human vascular endothelium. It is also found on bone marrow proerythroblasts, activated monocytes, and lymphoblasts in childhood leukemia. Endoglin is a component of the transforming growth factor-beta (TGFB) receptor complex and binds TGFB1 (<a href="/entry/190180">190180</a>) with high affinity (<a href="#31" class="mim-tip-reference" title="Rius, C., Smith, J. D., Almendro, N., Langa, C., Botella, L. M., Marchuk, D. A., Vary, C. P. H., Bernabeu, C. <strong>Cloning of the promoter region of human endoglin, the target gene for hereditary hemorrhagic telangiectasia type 1.</strong> Blood 92: 4677-4690, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9845534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9845534</a>]" pmid="9845534">Rius et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9845534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Gougos, A., Letarte, M. <strong>Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells.</strong> J. Biol. Chem. 265: 8361-8364, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1692830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1692830</a>]" pmid="1692830">Gougos and Letarte (1990)</a> isolated a cDNA encoding ENG lacking a leader sequence from an endothelial cell cDNA library. By screening a leukemia cell cDNA library, <a href="#4" class="mim-tip-reference" title="Bellon, T., Corbi, A., Lastres, P., Cales, C., Cebrian, M., Vera, S., Cheifetz, S., Massague, J., Letarte, M., Bernabeu, C. <strong>Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions.</strong> Europ. J. Immun. 23: 2340-2345, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8370410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8370410</a>] [<a href="https://doi.org/10.1002/eji.1830230943" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8370410">Bellon et al. (1993)</a> obtained full-length cDNAs encoding 2 variants of ENG. Both contain a 25-amino acid leader peptide, followed by 561 residues in the extracellular portion and a 25-amino acid transmembrane sequence. However, the long variant has a 47-amino acid cytoplasmic tail, while the tail of the short variant contains only 14 residues. Flow cytometric and immunoprecipitation analyses indicated high expression of both the 160- and 170-kD disulfide-linked homodimer ENG variants at the cell surface. RT-PCR analysis detected expression of both variants on activated monocytes, endothelial cells, and placenta, with the long form being predominant. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1692830+8370410" 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="#24" class="mim-tip-reference" title="McAllister, K. A., Grogg, K. M., Johnson, D. W., Gallione, C. J., Baldwin, M. A., Jackson, C. E., Helmbold, E. A., Markel, D. S., McKinnon, W. C., Murrell, J., McCormick, M. K., Pericak-Vance, M. A., Heutink, P., Oostra, B. A., Haitjema, T., Westerman, C. J. J., Porteous, M. E., Guttmacher, A. E., Letarte, M., Marchuk, D. A. <strong>Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.</strong> Nature Genet. 8: 345-351, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7894484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7894484</a>] [<a href="https://doi.org/10.1038/ng1294-345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7894484">McAllister et al. (1994)</a> concluded that the coding region of the ENG gene contains 14 exons. They thought it likely that there are additional exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7894484" 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 DNA from human-hamster somatic cell hybrids, <a href="#9" class="mim-tip-reference" title="Fernandez-Ruiz, E., St. Jacques, S., Bellon, T., Letarte, M., Bernabeu, C. <strong>Assignment of the human endoglin gene (END) to 9q34-qter.</strong> Cytogenet. Cell Genet. 64: 204-207, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8404038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8404038</a>] [<a href="https://doi.org/10.1159/000133576" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8404038">Fernandez-Ruiz et al. (1993)</a> mapped the ENG gene to human chromosome 9. By fluorescence in situ hybridization, they regionalized the assignment to 9q34-qter, distal to the breakpoint of the Philadelphia chromosome. The mouse endoglin locus is genetically inseparable from the adenylate kinase-1 locus (<a href="#29" class="mim-tip-reference" title="Pilz, A., Woodward, K., Peters, J., Povey, S., Abbott, C. <strong>Comparative mapping of 38 human chromosome 9 loci in the laboratory mouse. (Abstract)</strong> Ann. Hum. Genet. 58: 231-232, 1994."None>Pilz et al., 1994</a>). Thus, the ENG gene is probably located in the 9q34.1 region in the human. <a href="#30" class="mim-tip-reference" title="Qureshi, S. T., Gros, P., Letarte, M., Malo, D. <strong>The murine endoglin gene (Eng) maps to chromosome 2.</strong> Genomics 26: 165-166, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7782079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7782079</a>] [<a href="https://doi.org/10.1016/0888-7543(95)80099-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7782079">Qureshi et al. (1995)</a> mapped the mouse ENG homolog to chromosome 2, near the nebulin locus (<a href="/entry/161650">161650</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8404038+7782079" 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="Bellon, T., Corbi, A., Lastres, P., Cales, C., Cebrian, M., Vera, S., Cheifetz, S., Massague, J., Letarte, M., Bernabeu, C. <strong>Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions.</strong> Europ. J. Immun. 23: 2340-2345, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8370410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8370410</a>] [<a href="https://doi.org/10.1002/eji.1830230943" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8370410">Bellon et al. (1993)</a> found that both isoforms of ENG could bind TGFB1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8370410" 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="#31" class="mim-tip-reference" title="Rius, C., Smith, J. D., Almendro, N., Langa, C., Botella, L. M., Marchuk, D. A., Vary, C. P. H., Bernabeu, C. <strong>Cloning of the promoter region of human endoglin, the target gene for hereditary hemorrhagic telangiectasia type 1.</strong> Blood 92: 4677-4690, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9845534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9845534</a>]" pmid="9845534">Rius et al. (1998)</a> cloned and characterized the promoter region of the ENG gene. They showed that the endoglin promoter exhibits inducibility in the presence of TGFB1, suggesting possible therapeutic treatments in HHT1 (<a href="/entry/187300">187300</a>) patients, in which the expression level of the normal endoglin allele might not reach the threshold required for its function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9845534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Grisanti, S., Canbek, S., Kaiserling, E., Adam, A., Lafaut, B., Gelisken, F., Szurman, P., Henke-Fahle, S., Oficjalska-Mlynczak, J., Bartz-Schmidt, K. U. <strong>Expression of endoglin in choroidal neovascularization.</strong> Exp. Eye Res. 78: 207-213, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14729353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14729353</a>] [<a href="https://doi.org/10.1016/j.exer.2003.11.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14729353">Grisanti et al. (2004)</a> analyzed endoglin expression in choroidal neovascular membranes (CNVMs) surgically excised from eyes with age-related macular degeneration (ARMD; see <a href="/entry/153800">153800</a>). Endoglin expression was increased in the endothelial cells of CNVMs but was rarely associated with a concomitant expression of the proliferation marker Ki-67 (<a href="/entry/176741">176741</a>). The authors concluded that the elevated expression of endoglin in the surgically excised CNVMs suggested a persisting postmitotic activation in an advanced stage of neovascular tissue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14729353" 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>Hereditary hemorrhagic telangiectasia (see <a href="/entry/187300">187300</a>) and cerebral cavernous malformations (see <a href="/entry/116860">116860</a>) are disorders involving disruption of normal vascular morphogenesis. The autosomal dominant mode of inheritance in both of these disorders suggested to <a href="#23" class="mim-tip-reference" title="Marchuk, D. A., Srinivasan, S., Squire, T. L., Zawistowski, J. S. <strong>Vascular morphogenesis: tales of two syndromes.</strong> Hum. Molec. Genet. 12(R1): R97-R112, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12668602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12668602</a>] [<a href="https://doi.org/10.1093/hmg/ddg103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12668602">Marchuk et al. (2003)</a> that their underlying genes might regulate critical aspects of vascular morphogenesis. The authors summarized the roles of these genes, endoglin, KRIT1 (<a href="/entry/604214">604214</a>), and ALK1 (ACVRL1; <a href="/entry/601284">601284</a>), in the genetic control of angiogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12668602" 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="Lebrin, F., Goumans, M.-J., Jonker, L., Carvalho, R. L. C., Valdimarsdottir, G., Thorikay, M., Mummery, C., Arthur, H. M., ten Dijke, P. <strong>Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction.</strong> EMBO J. 23: 4018-4028, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15385967/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15385967</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15385967[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/10.1038/sj.emboj.7600386" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15385967">Lebrin et al. (2004)</a> found that mouse endothelial cells lacking endoglin did not grow because Tgfb/Alk1 signaling was reduced and Tgfb/Alk5 (<a href="/entry/190181">190181</a>) signaling was increased. Surviving cells adapted to the imbalance and proliferated by downregulating Alk5 expression. <a href="#17" class="mim-tip-reference" title="Lebrin, F., Goumans, M.-J., Jonker, L., Carvalho, R. L. C., Valdimarsdottir, G., Thorikay, M., Mummery, C., Arthur, H. M., ten Dijke, P. <strong>Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction.</strong> EMBO J. 23: 4018-4028, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15385967/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15385967</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15385967[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/10.1038/sj.emboj.7600386" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15385967">Lebrin et al. (2004)</a> concluded that endoglin has a role in the balance of ALK1 and ALK5 signaling to regulate endothelial cell proliferation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15385967" 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>GIPC1 (<a href="/entry/605072">605072</a>) is a scaffolding protein that regulates cell surface receptor expression and trafficking. Using predominantly embryonic mouse endothelial cell lines, <a href="#19" class="mim-tip-reference" title="Lee, N. Y., Ray, B., How, T., Blobe, G. C. <strong>Endoglin promotes transforming growth factor beta-mediated Smad 1/5/8 signaling and inhibits endothelial cell migration through its association with GIPC.</strong> J. Biol. Chem. 283: 32527-32533, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18775991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18775991</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18775991[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.M803059200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18775991">Lee et al. (2008)</a> showed that endoglin and Gipc interacted directly. The interaction enhanced TGF-beta-1-induced phosphorylation of Smad1 (<a href="/entry/601595">601595</a>)/Smad5 (<a href="/entry/603110">603110</a>)/Smad8 (SMAD9; <a href="/entry/603295">603295</a>), increased a Smad1/Smad5/Smad8-responsive promoter, and inhibited endothelial cell migration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18775991" 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="Chen, Y., Hao, Q., Kim, H., Su, H., Letarte, M., Karumanchi, S. A., Lawton, M. T., Barbaro, N. M., Yang, G.-Y., Young, W. L. <strong>Soluble endoglin modulates aberrant cerebral vascular remodeling.</strong> Ann. Neurol. 66: 19-27, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19670444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19670444</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19670444[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/ana.21710" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19670444">Chen et al. (2009)</a> found increased levels of soluble endoglin in vascular surgical specimens from 33 patients with arteriovenous malformations of the brain (BAVM; <a href="/entry/108010">108010</a>) compared to similar specimens from 8 epileptic patients. However, there was no difference in expression of membrane-bound endoglin and no difference in plasma soluble endoglin between BAVM patients and controls. Transduction of soluble endoglin in mouse brain resulted in the formation of abnormal and dysplastic capillary structures, and was associated with increased levels of matrix metalloproteinase activity and oxidative radicals. <a href="#7" class="mim-tip-reference" title="Chen, Y., Hao, Q., Kim, H., Su, H., Letarte, M., Karumanchi, S. A., Lawton, M. T., Barbaro, N. M., Yang, G.-Y., Young, W. L. <strong>Soluble endoglin modulates aberrant cerebral vascular remodeling.</strong> Ann. Neurol. 66: 19-27, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19670444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19670444</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19670444[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/ana.21710" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19670444">Chen et al. (2009)</a> suggested that soluble endoglin may play a role in the formation of sporadic BAVM by acting as a decoy receptor, resulting in inhibition of TGF-beta signaling and functional haploinsufficiency of ENG, as observed in patients with HHT1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19670444" 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="Muenzner, P., Bachmann, V., Zimmermann, W., Hentschel, J., Hauck, C. R. <strong>Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation.</strong> Science 329: 1197-1201, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20813953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20813953</a>] [<a href="https://doi.org/10.1126/science.1190892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20813953">Muenzner et al. (2010)</a> found that CEA (<a href="/entry/114890">114890</a>)-binding bacteria colonized the urogenital tract of CEA transgenic mice, but not of wildtype mice, by suppressing exfoliation of mucosal cells. CEA binding triggered de novo expression of the transforming growth factor receptor CD105, changing focal adhesion composition and activating beta-1 integrins (<a href="/entry/135630">135630</a>). <a href="#25" class="mim-tip-reference" title="Muenzner, P., Bachmann, V., Zimmermann, W., Hentschel, J., Hauck, C. R. <strong>Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation.</strong> Science 329: 1197-1201, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20813953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20813953</a>] [<a href="https://doi.org/10.1126/science.1190892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20813953">Muenzner et al. (2010)</a> concluded that this manipulation of integrin inside-out signaling promotes efficient mucosal colonization and represents a potential target to prevent or cure bacterial infections. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20813953" 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="#37" class="mim-tip-reference" title="Wang, X., Abraham, S., McKenzie, J. A. G., Jeffs, N., Swire, M., Tripathi, V. B., Luhmann, U. F. O., Lange, C. A. K., Zhai, Z., Arthur, H. M., Bainbridge, J. W. B., Moss, S. E., Greenwood, J. <strong>LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling.</strong> Nature 499: 306-311, 2013. Note: Erratum: Nature 501: 578 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23868260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23868260</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23868260[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/10.1038/nature12345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23868260">Wang et al. (2013)</a> identified upregulation of Lrg1 (<a href="/entry/611289">611289</a>) in the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology. The authors showed that in the presence of transforming growth factor-beta-1 (TGFB1; <a href="/entry/190180">190180</a>), Lrg1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 developed a mild retinal vascular phenotype but exhibited a significant reduction in pathologic ocular angiogenesis. Lrg1 bound directly to the Tgf-beta accessory receptor endoglin, which, in the presence of TGF-beta-1, resulted in promotion of the proangiogenic Smad1/5/8 signaling pathway. Lrg1 antibody blockade inhibited this switch and attenuated angiogenesis. <a href="#37" class="mim-tip-reference" title="Wang, X., Abraham, S., McKenzie, J. A. G., Jeffs, N., Swire, M., Tripathi, V. B., Luhmann, U. F. O., Lange, C. A. K., Zhai, Z., Arthur, H. M., Bainbridge, J. W. B., Moss, S. E., Greenwood, J. <strong>LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling.</strong> Nature 499: 306-311, 2013. Note: Erratum: Nature 501: 578 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23868260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23868260</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23868260[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/10.1038/nature12345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23868260">Wang et al. (2013)</a> concluded that these studies revealed that LRG1 is a regulator of angiogenesis that mediates its effect by modulating TGF-beta signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23868260" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a panel of 68 DNA samples from probands of unrelated hereditary hemorrhagic telangiectasia (see HHT1; <a href="/entry/187300">187300</a>) families, most of whom were members of kindreds with pulmonary arteriovenous malformations (PAVMs), <a href="#24" class="mim-tip-reference" title="McAllister, K. A., Grogg, K. M., Johnson, D. W., Gallione, C. J., Baldwin, M. A., Jackson, C. E., Helmbold, E. A., Markel, D. S., McKinnon, W. C., Murrell, J., McCormick, M. K., Pericak-Vance, M. A., Heutink, P., Oostra, B. A., Haitjema, T., Westerman, C. J. J., Porteous, M. E., Guttmacher, A. E., Letarte, M., Marchuk, D. A. <strong>Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.</strong> Nature Genet. 8: 345-351, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7894484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7894484</a>] [<a href="https://doi.org/10.1038/ng1294-345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7894484">McAllister et al. (1994)</a> identified mutations in the ENG gene in 3 affected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7894484" 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="#34" class="mim-tip-reference" title="Shovlin, C. L., Hughes, J. M. B., Scott, J., Seidman, C. E., Seidman, J. G. <strong>Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia.</strong> Am. J. Hum. Genet. 61: 68-79, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245986</a>] [<a href="https://doi.org/10.1086/513906" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9245986">Shovlin et al. (1997)</a> identified 7 novel mutations in the ENG gene in 8 families. Two of the mutations (a termination codon in exon 4 and a large genomic deletion extending 3-prime of intron 8) did not produce a stable ENG transcript in lymphocytes. Five other mutations (2 donor splice site mutations (e.g., <a href="#0004">131195.0004</a>) and 3 deletions) produced altered mRNAs that were predicted to encode markedly truncated ENG proteins. These data suggested that the molecular mechanism by which ENG mutations cause HHT is haploinsufficiency. Furthermore, because the clinical manifestation of disease in these 8 families was similar, <a href="#34" class="mim-tip-reference" title="Shovlin, C. L., Hughes, J. M. B., Scott, J., Seidman, C. E., Seidman, J. G. <strong>Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia.</strong> Am. J. Hum. Genet. 61: 68-79, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245986</a>] [<a href="https://doi.org/10.1086/513906" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9245986">Shovlin et al. (1997)</a> hypothesized that phenotypic variation of HHT is not related to a particular ENG mutation. They found that 41% (23 of 56) of HHT patients with ENG mutations had pulmonary arteriovenous malformations, whereas a significantly smaller fraction, 14% (5 of 35), of HHT patients in whom linkage analyses indicated non-ENG mutations had PAVMs (P less than 0.01). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9245986" 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 newborn from a family with HHT, <a href="#27" class="mim-tip-reference" title="Pece, N., Vera, S., Cymerman, U., White, R. I., Jr., Wrana, J. L., Letarte, M. <strong>Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative.</strong> J. Clin. Invest. 100: 2568-2579, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9366572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9366572</a>] [<a href="https://doi.org/10.1172/JCI119800" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9366572">Pece et al. (1997)</a> identified a novel endoglin splice site mutation (<a href="#0005">131195.0005</a>) that resulted in skipping of exon 3 and the expression of a mutant protein missing 47 amino acids but with an intact transmembrane region. This mutant protein was considered particularly suited for testing the dominant-negative model as it is more likely to be expressed at the cell surface than truncated ones. However, it was detectable only by metabolic labeling, did not form heterodimers with normal endoglin, and did not reach the cell surface. In activated monocytes from 3 patients with known truncations, no mutant protein could be detected. However, when cDNA corresponding to 2 other HHT1 endoglin truncations were overexpressed in COS-1 cells, mutant proteins could be detected intracellularly, were not secreted, and did not form heterodimers with wildtype endoglin. Thus, <a href="#27" class="mim-tip-reference" title="Pece, N., Vera, S., Cymerman, U., White, R. I., Jr., Wrana, J. L., Letarte, M. <strong>Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative.</strong> J. Clin. Invest. 100: 2568-2579, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9366572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9366572</a>] [<a href="https://doi.org/10.1172/JCI119800" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9366572">Pece et al. (1997)</a> concluded that mutant endoglin in HHT patients appears to be only transiently expressed and not to represent a dominant negative. The data strongly suggested that a reduced level of functional endoglin leads to the abnormalities seen in HHT1 patients. In these studies, expression of normal and mutant endoglin proteins was analyzed in umbilical vein endothelial cells from the baby and in activated monocytes from the affected father. In both samples, only normal dimeric endoglin (160 kD) was observed at the cell surface, at 50% of control levels. Despite an intact transmembrane region, mutant protein was detectable only by metabolic labeling, as an intracellular homodimer of 130 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9366572" 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="Gallione, C. J., Klaus, D. J., Yeh, E. Y., Stenzel, T. T., Xue, Y., Anthony, K. B., McAllister, K. A., Baldwin, M. A., Berg, J. N., Lux, A., Smith, J. D., Vary, C. P. H., Craigen, W. J., Westermann, C. J. J., Warner, M. L., Miller, Y. E., Jackson, C. E., Guttmacher, A. E., Marchuk, D. A. <strong>Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.</strong> Hum. Mutat. 11: 286-294, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554745</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<286::AID-HUMU6>3.0.CO;2-B" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9554745">Gallione et al. (1998)</a> described 11 novel ENG mutations in HHT kindreds, which included missense and splice site mutations. In 2 unrelated families, they identified a T-to-C transition in the ATG initiation codon, which converted the initiator methionine to threonine. Non-ATG codons can initiate at 3 to 5% of normal translation levels when flanked by specific consensus sequences (<a href="#15" class="mim-tip-reference" title="Kozak, M. <strong>Context effects and inefficient initiation at non-AUG codons in eucaryotic cell-free translation systems.</strong> Molec. Cell. Biol. 9: 5073-5080, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2601709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2601709</a>] [<a href="https://doi.org/10.1128/mcb.9.11.5073-5080.1989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2601709">Kozak, 1989</a>). However, the sequence context of the specific mutation in the 2 HHT families did not fit the consensus for even such reduced initiation. The first potential in-frame initiation codon was within exon 5. If protein synthesis was initiated at this position, the product would lack the signal peptide for proper membrane trafficking, as well as 30% of the N-terminal residues. This initiation codon mutation appeared to be a classic null allele that eliminated the translation of the endoglin protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9554745+2601709" 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="Pece-Barbara, N., Cymerman, U., Vera, S., Marchuk, D. A., Letarte, M. <strong>Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1.</strong> Hum. Molec. Genet. 8: 2171-2181, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545596</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545596">Pece-Barbara et al. (1999)</a> stated that to that date 29 different mutations had been reported in HHT1 in the endoglin gene and 18 distinct mutations had been described for the ALK1 gene (<a href="/entry/601284">601284</a>), which underlies type 2 hereditary hemorrhagic telangiectasia (HHT2; <a href="/entry/600376">600376</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545596" 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>Although a dominant-negative model of endoglin dysfunction was initially proposed for HHT1, <a href="#27" class="mim-tip-reference" title="Pece, N., Vera, S., Cymerman, U., White, R. I., Jr., Wrana, J. L., Letarte, M. <strong>Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative.</strong> J. Clin. Invest. 100: 2568-2579, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9366572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9366572</a>] [<a href="https://doi.org/10.1172/JCI119800" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9366572">Pece et al. (1997)</a> observed a mutant protein (<a href="#0005">131195.0005</a>) that was transiently expressed intracellularly both in monocytes from an HHT1 patient and in human umbilical vein endothelial cells (HUVECs) from the child of the patient. As the cell surface-expressed protein was still able to associate with the TGF-beta receptor complex, this indicated that it is the reduction in the level of surface endoglin, rather than interference by mutant protein, that is involved in the generation of HHT1. The description of 3 null mutations where mRNA transcripts were undetectable again suggested that endoglin haploinsufficiency is the molecular basis for HHT1. The observation that every HHT1 family so far studied was found to have a distinct mutation and that mutations of all types are distributed throughout the gene was again consistent with a haploinsufficiency model. <a href="#28" class="mim-tip-reference" title="Pece-Barbara, N., Cymerman, U., Vera, S., Marchuk, D. A., Letarte, M. <strong>Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1.</strong> Hum. Molec. Genet. 8: 2171-2181, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545596</a>] [<a href="https://doi.org/10.1093/hmg/8.12.2171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10545596">Pece-Barbara et al. (1999)</a> studied 4 missense mutations and found that none was significantly expressed at the surface of COS-1 transfectants. Thus, although these 4 HHT1 missense mutations led to transient intracellular species, they cannot interfere with normal endoglin function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9366572+10545596" 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>To determine whether mechanisms other than haploinsufficiency might be involved in HHT1, <a href="#22" class="mim-tip-reference" title="Lux, A., Gallione, C. J., Marchuk, D. A. <strong>Expression analysis of endoglin missense and truncation mutations: insights into protein structure and disease mechanisms.</strong> Hum. Molec. Genet. 9: 745-755, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749981</a>] [<a href="https://doi.org/10.1093/hmg/9.5.745" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10749981">Lux et al. (2000)</a> investigated 8 different mutations in the ENG gene. Missense mutants were expressed but apparently misfolded, and most showed no cell surface expression. When coexpressed with wildtype endoglin, missense mutants were able to dimerize with normal endoglin protein and were transported to the cell surface. The protein product of one truncation mutation was unable to dimerize with normal endoglin, and likely acts through haploinsufficiency. On the contrary, the delta-GC frameshift mutation (<a href="#0003">131195.0003</a>) was able to dimerize with normal endoglin, and likely acts in a dominant-negative fashion by interfering with protein processing or cell surface expression. Thus, the authors concluded that either dominant-negative protein interactions or haploinsufficiency can cause HHT1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10749981" 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>To maximize the detection of potential mutant proteins, <a href="#26" class="mim-tip-reference" title="Paquet, M.-E., Pece-Barbara, N., Vera, S., Cymerman, U., Karabegovic, A., Shovlin, C., Letarte, M. <strong>Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function.</strong> Hum. Molec. Genet. 10: 1347-1357, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11440987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11440987</a>] [<a href="https://doi.org/10.1093/hmg/10.13.1347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11440987">Paquet et al. (2001)</a> utilized pulse-chase experiments to analyze the expression of large truncation mutations and missense mutations in cells from HHT1 patients with 13 unique mutations. All HHT1 mutants analyzed, although expressed to various degrees in COS-1 cells, were either undetectable, present at low levels as transient intracellular forms, or expressed as partially glycosylated precursors in endogenous cells. The mutants did not form heterodimers with normal endoglin and did not interfere with its normal trafficking to the cell surface, further supporting the haploinsufficiency model. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11440987" 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 COS-1 transfected cells, <a href="#2" class="mim-tip-reference" title="Abdalla, S. A., Pece-Barbara, N., Vera, S., Tapia, E., Paez, E., Bernabeu, C., Letarte, M. <strong>Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2.</strong> Hum. Molec. Genet. 9: 1227-1237, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10767348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10767348</a>] [<a href="https://doi.org/10.1093/hmg/9.8.1227" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10767348">Abdalla et al. (2000)</a> determined that ALK1 was found in the TGFB1 and -B3 (<a href="/entry/190230">190230</a>) receptor complexes in association with endoglin and TGFBR2 (<a href="/entry/190182">190182</a>), but not in activin (see <a href="/entry/147290">147290</a>) receptor complexes containing endoglin. In HUVEC, ALK1 was not detectable in TGFB1 or -B3 receptor complexes. However, in the absence of ligand, ALK1 and endoglin interactions were observed by immunoprecipitation/Western blot in HUVEC from normal as well as HHT1 and HHT2 patients. The authors hypothesized that a transient association between ALK1 and endoglin is required at a critical level to ensure vessel wall integrity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10767348" 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="Cymerman, U., Vera, S., Karabegovic, A., Abdalla, S., Letarte, M. <strong>Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasia.</strong> Hum. Mutat. 21: 482-492, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12673790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12673790</a>] [<a href="https://doi.org/10.1002/humu.10203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12673790">Cymerman et al. (2003)</a> optimized a quantitative multiplex PCR (QMPCR) analysis to efficiently detect deletions and insertions in the ENG gene in HHT1 patients from 18 families. They reported 17 novel mutations, of which 6 were detected by QMPCR. Review of 80 HHT1 families (62 previously reported and the 18 described) indicated that 10% would not have been resolved by sequencing and that an additional 25% could be revealed by QMPCR performed before sequencing. Thus the use of QMPCR can accelerate genetic screening for HHT1 and resolve mutations affecting whole exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12673790" 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="#16" class="mim-tip-reference" title="Lastella, P., Sabba, C., Lenato, G. M., Resta, N., Lattanzi, W., Gallitelli, M., Cirulli, A., Guanti, G. <strong>Endoglin gene mutations and polymorphisms in Italian patients with hereditary haemorrhagic telangiectasia.</strong> Clin. Genet. 63: 536-540, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12786761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12786761</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2003.00081.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12786761">Lastella et al. (2003)</a> detected 4 novel and 1 previously reported mutation in the ENG gene in Italian patients with HHT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12786761" 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 160 unrelated cases of HHT, <a href="#20" class="mim-tip-reference" title="Lesca, G., Plauchu, H., Coulet, F., Lefebvre, S., Plessis, G., Odent, S., Riviere, S., Leheup, B., Goizet, C., Carette, M.-F., Cordier, J.-F., Pinson, S., Soubrier, F., Calender, A., Giraud, S. <strong>Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France.</strong> Hum. Mutat. 23: 289-299, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15024723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15024723</a>] [<a href="https://doi.org/10.1002/humu.20017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15024723">Lesca et al. (2004)</a> screened the coding sequences of the ENG and ALK1 genes. Germline mutations were identified in 100 patients (62.5%): 36 of the mutations were in ENG and 64 were in ALK1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15024723" 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 7 Danish HHT families, <a href="#6" class="mim-tip-reference" title="Brusgaard, K., Kjeldsen, A. D., Poulsen, L., Moss, H., Vase, P., Rasmussen, K., Kruse, T. A., Horder, M. <strong>Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia.</strong> Clin. Genet. 66: 556-561, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15521985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15521985</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00341.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15521985">Brusgaard et al. (2004)</a> identified a novel nonsense mutation (<a href="#0009">131195.0009</a>) in the ENG gene, which they characterized as a founder mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15521985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Abdalla, S. A., Letarte, M. <strong>Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease.</strong> J. Med. Genet. 43: 97-110, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15879500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15879500</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15879500[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/10.1136/jmg.2005.030833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15879500">Abdalla and Letarte (2006)</a> tabulated the known ENG mutations identified in hereditary hemorrhagic telangiectasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15879500" 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="Bayrak-Toydemir, P., McDonald, J., Markewitz, B., Lewin, S., Miller, F., Chou, L.-S., Gedge, F., Tang, W., Coon, H., Mao, R. <strong>Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations.</strong> Am. J. Med. Genet. 140A: 463-470, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16470787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16470787</a>] [<a href="https://doi.org/10.1002/ajmg.a.31101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16470787">Bayrak-Toydemir et al. (2006)</a> identified mutations in 26 (76%) of 34 kindreds with HHT. Fourteen (54%) mutations were in the ENG gene, consistent with HHT1, and 12 (46%) were in the ACVRL1 gene, consistent with HHT2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16470787" 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="#38" class="mim-tip-reference" title="Wehner, L.-E., Folz, B. J., Argyriou, L., Twelkemeyer, S., Teske, U., Geisthoff, U. W., Werner, J. A., Engel, W., Nayernia, K. <strong>Mutation analysis in hereditary haemorrhagic telangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1 mutations.</strong> Clin. Genet. 69: 239-245, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16542389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16542389</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00574.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16542389">Wehner et al. (2006)</a> identified mutations in 32 (62.7%) of 51 unrelated German patients with HHT. Among these mutations, 11 of 13 ENG mutations and 12 of 17 ACVRL1 mutations were not previously reported in the literature. Analysis of genotype/phenotype correlations was consistent with a more common frequency of PAVMs in patients with ENG mutations (HHT1). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16542389" 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="#36" class="mim-tip-reference" title="Sweet, K., Willis, J., Zhou, X.-P., Gallione, C., Sawada, T., Alhopuro, P., Khoo, S. K., Patocs, A., Martin, C., Bridgeman, S., Heinz, J., Pilarski, R., Lehtonen, R., Prior, T. W., Frebourg, T., Teh, B. T., Marchuk, D. A., Aaltonen, L. A., Eng, C. <strong>Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.</strong> JAMA 294: 2465-2473, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16287957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16287957</a>] [<a href="https://doi.org/10.1001/jama.294.19.2465" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16287957">Sweet et al. (2005)</a> sequenced the ENG gene in 14 patients with juvenile polyposis syndrome (JPS; <a href="/entry/174900">174900</a>) who were negative for mutation in the 2 known JPS genes, SMAD4 (<a href="/entry/600993">600993</a>) and BMPR1A (<a href="/entry/601299">601299</a>), and identified germline missense mutations in the ENG gene in 2 patients, respectively. The mutations were not found in 105 North American controls. In 3 of 31 patients with JPS who were negative for mutations in the SMAD4 and BMPR1A genes, <a href="#14" class="mim-tip-reference" title="Howe, J. R., Haidle, J. L., Lal, G., Bair, J., Song, C., Pechman, B., Chinnathambi, S., Lynch, H. T. <strong>ENG mutations in MADH4/BMPR1A mutation negative patients with juvenile polyposis. (Letter)</strong> Clin. Genet. 71: 91-92, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17204053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17204053</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00734.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17204053">Howe et al. (2007)</a> identified 2 different nonsynonymous substitutions that had been previously identified as polymorphisms in patients with HTT. <a href="#14" class="mim-tip-reference" title="Howe, J. R., Haidle, J. L., Lal, G., Bair, J., Song, C., Pechman, B., Chinnathambi, S., Lynch, H. T. <strong>ENG mutations in MADH4/BMPR1A mutation negative patients with juvenile polyposis. (Letter)</strong> Clin. Genet. 71: 91-92, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17204053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17204053</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00734.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17204053">Howe et al. (2007)</a> stated that their findings did not confirm the suggestion that the ENG gene predisposes for JPS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16287957+17204053" 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 German woman with clinical features of HHT and negative direct sequencing results, <a href="#33" class="mim-tip-reference" title="Shoukier, M., Teske, U., Weise, A., Engel, W., Argyriou, L. <strong>Characterization of five novel large deletions causing hereditary haemorrhagic telangiectasia.</strong> Clin. Genet. 73: 320-330, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18312453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18312453</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.00968.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18312453">Shoukier et al. (2008)</a> identified a deletion of exon 4 of the ENG gene using quantitative real-time polymerase chain reaction (qRT-PCR) and confirmed by multiplex ligation-dependent probe amplification (MLPA). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18312453" 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 3-generation Spanish family with HHT that was negative for mutation after screening with an HHT gene panel, <a href="#32" class="mim-tip-reference" title="Ruiz-Llorente, L., McDonald, J., Wooderchak-Donahue, W., Briggs, E., Chesnutt, M., Bayrak-Toydemir, P., Bernabeu, C. <strong>Characterization of a family mutation in the 5-prime untranslated region of the endoglin gene causative of hereditary hemorrhagic telangiectasia.</strong> J. Hum. Genet. 64: 333-339, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30728427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30728427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30728427[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/10.1038/s10038-019-0564-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30728427">Ruiz-Llorente et al. (2019)</a> sequenced the 5-prime UTR of the ENG gene and identified a variant (c.-142A-T; <a href="#0010">131195.0010</a>) that creates a putative AUG initiation codon at -141 bases from the constitutive translation initiation codon. Functional analysis demonstrated markedly reduced expression with the mutant compared to control ENG. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30728427" 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>From a cohort of 274 sequenced patients with genetically unresolved HHT, <a href="#35" class="mim-tip-reference" title="Soukarieh, O., Tillet, E., Proust, C., Dupont, C., Jaspard-Vinassa, B., Soubrier, F., Goyenvalle, A., Eyries, M., Tregouet, D. A. <strong>uAUG creating variants in the 5-prime-UTR of ENG causing hereditary hemorrhagic telangiectasia.</strong> NPJ Genomic Med. 8: 32, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37848456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37848456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=37848456[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/10.1038/s41525-023-00378-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="37848456">Soukarieh et al. (2023)</a> identified 2 patients with mutations in the 5-prime UTR of the ENG gene, c.-79C-T and c.-68G-A, which were confirmed by Sanger sequencing. Functional analysis of these 2 variants as well as 3 additional previously published 5-prime UTR ENG variants identified in HHT patients, including the c.142A-T mutation, revealed that all 5 variants created upstream AUGs at the origin of upstream overlapping open reading frames (uoORFs) ending at the same stop codon (c.125), and all showed altered protein levels and function. Experiments using constructs in which the canonical start site had been deleted revealed that the identified upstream AUGs could initiate translation, suggesting that the associated effects were translation-dependent. The authors noted that all of the uoORF-creating variants studied showed ENG protein levels and BMP response element (BRE) activity that were less than 40% and 50%, respectively, compared to wildtype ENG, and were associated with severe HHT symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37848456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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The Eng -/- embryos exhibited an absence of vascular organization and the presence of multiple pockets of red blood cells on the surface of the yolk sac. Epithelial marker expression was not disrupted in Eng -/- mice. There was persistence of an immature perineural vascular plexus, indicating a failure of endothelial remodeling in Eng -/- embryos. At embryonic day 10.5, the cardiac tube did not complete rotation and was associated with a serosanguinous pericardial effusion. By embryonic day 10.5, the major vessels including the dorsal aortae, intersomitic vessels, branchial arches, and carotid arteries were atretic and disorganized in Eng -/- embryos. There was also poor vascular smooth muscle cell formation at both embryonic days 9.5 and 10.5. These vascular smooth muscle cell abnormalities preceded the differences in endothelial organization. In contrast to mice lacking TGF-beta, vasculogenesis was unaffected. <a href="#21" class="mim-tip-reference" title="Li, D. Y., Sorensen, L. K., Brooke, B. S., Urness, L. D., Davis, E. C., Taylor, D. G., Boak, B. B., Wendel, D. P. <strong>Defective angiogenesis in mice lacking endoglin.</strong> Science 284: 1534-1537, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10348742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10348742</a>] [<a href="https://doi.org/10.1126/science.284.5419.1534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10348742">Li et al. (1999)</a> concluded that their results demonstrated that endoglin is essential for angiogenesis and suggest a pathogenic mechanism for HHT1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10348742" 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="Bourdeau, A., Dumont, D. J., Letarte, M. <strong>A murine model of hereditary hemorrhagic telangiectasia.</strong> J. Clin. Invest. 104: 1343-1351, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10562296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10562296</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10562296[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/JCI8088" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10562296">Bourdeau et al. (1999)</a> likewise generated mice lacking 1 or both copies of the endoglin gene. Endoglin null embryos died at gestational day 10.0-10.5 due to defects in vessel and heart development. Vessel formation appeared normal until hemorrhage occurred in yolk sacs and embryos. The primitive vascular plexus of the yolk sac failed to mature into defined vessels, and vascular channels dilated and ruptured. Internal bleeding was seen in the peritoneal cavity, implying fragile vessels. Heart development was arrested at day 9.0, and the atrioventricular canal endocardium failed to undergo mesenchymal transformation and cushion-tissue formation. The data suggested that endoglin is critical for both angiogenesis and heart valve formation. Some heterozygotes showed signs of HHT, such as telangiectases or recurrent nosebleeds. In this murine model of HHT, it appeared that epigenetic factors and modifier genes, some of which are present in the 129/Ola strain, which shows expressing heterozygotes, contribute to disease heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10562296" 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="Lebrin, F., Srun, S., Raymond, K., Martin, S., van den Brink, S., Freitas, C., Breant, C., Mathivet, T., Larrivee, B., Thomas, J.-L., Arthur, H. M., Westermann, C. J. J., Disch, F., Mager, J. J., Snijder, R. J., Eichmann, A., Mummery, C. L. <strong>Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia.</strong> Nature Med. 16: 420-428, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20364125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20364125</a>] [<a href="https://doi.org/10.1038/nm.2131" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20364125">Lebrin et al. (2010)</a> showed that treatment of Eng +/- with thalidomide normalized inappropriate vessel formation and promoted pericyte and mural cell activation and vessel maturation via increased expression of Pdgfb (<a href="/entry/190040">190040</a>). In vitro studies of mouse tissue showed that thalidomide stimulated the recruitment of mural cells to the vessel branches, resulting in a stabilization of blood vessels and a rescue of vessel wall defects. Treatment reduced nosebleed frequency in 6 of 7 humans with HHT, and reduced the duration of nosebleeds in 3 of 4 for whom data were available. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20364125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=131195[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121918400 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918400;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/rs121918400?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=rs121918400" 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=rs121918400" 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 with hereditary hemorrhagic telangiectasia (HHT1; <a href="/entry/187300">187300</a>), <a href="#24" class="mim-tip-reference" title="McAllister, K. A., Grogg, K. M., Johnson, D. W., Gallione, C. J., Baldwin, M. A., Jackson, C. E., Helmbold, E. A., Markel, D. S., McKinnon, W. C., Murrell, J., McCormick, M. K., Pericak-Vance, M. A., Heutink, P., Oostra, B. A., Haitjema, T., Westerman, C. J. J., Porteous, M. E., Guttmacher, A. E., Letarte, M., Marchuk, D. A. <strong>Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.</strong> Nature Genet. 8: 345-351, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7894484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7894484</a>] [<a href="https://doi.org/10.1038/ng1294-345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7894484">McAllister et al. (1994)</a> found a C-to-G transition at nucleotide position 831 in the ENG gene, resulting in conversion of tyrosine-277 to a termination codon. The truncated protein resulting from this mutation would comprise only half of the extracellular domain and lack the membrane-spanning and cytoplasmic domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7894484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of a family with hereditary hemorrhagic telangiectasia (HHT1; <a href="/entry/187300">187300</a>), <a href="#24" class="mim-tip-reference" title="McAllister, K. A., Grogg, K. M., Johnson, D. W., Gallione, C. J., Baldwin, M. A., Jackson, C. E., Helmbold, E. A., Markel, D. S., McKinnon, W. C., Murrell, J., McCormick, M. K., Pericak-Vance, M. A., Heutink, P., Oostra, B. A., Haitjema, T., Westerman, C. J. J., Porteous, M. E., Guttmacher, A. E., Letarte, M., Marchuk, D. A. <strong>Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.</strong> Nature Genet. 8: 345-351, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7894484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7894484</a>] [<a href="https://doi.org/10.1038/ng1294-345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7894484">McAllister et al. (1994)</a> found deletion of 39 nucleotides (882 to 920) in exon 7 of the ENG gene, removing 13 amino acids from the protein and altering the first amino acid (position 307) in a potential N-linked glycosylation site. The mutation segregated only with affected members of the 3-generation family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7894484" 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 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</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">rs2131875838 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2131875838;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=rs2131875838" 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=rs2131875838" 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=RCV000018150 OR RCV003593861 OR RCV004791227" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018150, RCV003593861, RCV004791227" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018150...</a>
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<p>In affected members of a family with hereditary hemorrhagic telangiectasia (HHT1; <a href="/entry/187300">187300</a>), <a href="#24" class="mim-tip-reference" title="McAllister, K. A., Grogg, K. M., Johnson, D. W., Gallione, C. J., Baldwin, M. A., Jackson, C. E., Helmbold, E. A., Markel, D. S., McKinnon, W. C., Murrell, J., McCormick, M. K., Pericak-Vance, M. A., Heutink, P., Oostra, B. A., Haitjema, T., Westerman, C. J. J., Porteous, M. E., Guttmacher, A. E., Letarte, M., Marchuk, D. A. <strong>Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.</strong> Nature Genet. 8: 345-351, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7894484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7894484</a>] [<a href="https://doi.org/10.1038/ng1294-345" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7894484">McAllister et al. (1994)</a> found a 2-bp deletion (nucleotides 1553 and 1554) in exon 11 of the ENG gene that created a MaeIII restriction site and caused a frameshift with a premature termination after an additional 7 amino acids. The predicted truncated protein would lack the membrane-spanning and cytoplasmic domains of endoglin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7894484" 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">rs1564457752 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1564457752;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=rs1564457752" 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=rs1564457752" 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=RCV000018151 OR RCV001851903 OR RCV004018638 OR RCV004700247" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018151, RCV001851903, RCV004018638, RCV004700247" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018151...</a>
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<p>One of 7 novel mutations in the ENG gene found by <a href="#34" class="mim-tip-reference" title="Shovlin, C. L., Hughes, J. M. B., Scott, J., Seidman, C. E., Seidman, J. G. <strong>Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia.</strong> Am. J. Hum. Genet. 61: 68-79, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245986</a>] [<a href="https://doi.org/10.1086/513906" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9245986">Shovlin et al. (1997)</a> in patients with hereditary hemorrhagic telangiectasia-1 (HHT1; <a href="/entry/187300">187300</a>) was a deletion of exon 3 due to an A-to-G transition at position 4 of the donor splice site of intron 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9245986" 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">rs886039505 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886039505;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=rs886039505" 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=rs886039505" 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=RCV000255227 OR RCV000274164 OR RCV001034674 OR RCV002450790" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000255227, RCV000274164, RCV001034674, RCV002450790" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000255227...</a>
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<p>In a patient with hereditary hemorrhagic telangiectasia-1 (HHT1; <a href="/entry/187300">187300</a>), <a href="#27" class="mim-tip-reference" title="Pece, N., Vera, S., Cymerman, U., White, R. I., Jr., Wrana, J. L., Letarte, M. <strong>Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative.</strong> J. Clin. Invest. 100: 2568-2579, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9366572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9366572</a>] [<a href="https://doi.org/10.1172/JCI119800" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9366572">Pece et al. (1997)</a> detected a splice site mutation of the ENG gene, resulting in in-frame deletion of exon 3 from the transcript and a truncated polypeptide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9366572" 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 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
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ENG, MET1THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606783 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606783;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=rs267606783" 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=rs267606783" 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=RCV000018153 OR RCV002433460" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018153, RCV002433460" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018153...</a>
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<p>In 2 unrelated families with hereditary hemorrhagic telangiectasia-1 (HHT1; <a href="/entry/187300">187300</a>), <a href="#10" class="mim-tip-reference" title="Gallione, C. J., Klaus, D. J., Yeh, E. Y., Stenzel, T. T., Xue, Y., Anthony, K. B., McAllister, K. A., Baldwin, M. A., Berg, J. N., Lux, A., Smith, J. D., Vary, C. P. H., Craigen, W. J., Westermann, C. J. J., Warner, M. L., Miller, Y. E., Jackson, C. E., Guttmacher, A. E., Marchuk, D. A. <strong>Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.</strong> Hum. Mutat. 11: 286-294, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554745</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<286::AID-HUMU6>3.0.CO;2-B" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9554745">Gallione et al. (1998)</a> identified a missense mutation of the initiation codon of the ENG gene. A T-to-C transition converted ATG (met) to ACG (thr). Since flanking sequences did not satisfy the consensus sequences found by <a href="#15" class="mim-tip-reference" title="Kozak, M. <strong>Context effects and inefficient initiation at non-AUG codons in eucaryotic cell-free translation systems.</strong> Molec. Cell. Biol. 9: 5073-5080, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2601709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2601709</a>] [<a href="https://doi.org/10.1128/mcb.9.11.5073-5080.1989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2601709">Kozak (1989)</a> to permit initiation from non-ATG codons and the first potential in-frame initiation codon was within exon 5, <a href="#10" class="mim-tip-reference" title="Gallione, C. J., Klaus, D. J., Yeh, E. Y., Stenzel, T. T., Xue, Y., Anthony, K. B., McAllister, K. A., Baldwin, M. A., Berg, J. N., Lux, A., Smith, J. D., Vary, C. P. H., Craigen, W. J., Westermann, C. J. J., Warner, M. L., Miller, Y. E., Jackson, C. E., Guttmacher, A. E., Marchuk, D. A. <strong>Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.</strong> Hum. Mutat. 11: 286-294, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554745</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<286::AID-HUMU6>3.0.CO;2-B" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9554745">Gallione et al. (1998)</a> predicted that this would function as a classic null mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9554745+2601709" 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 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121918401 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918401;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/rs121918401?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=rs121918401" 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=rs121918401" 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=RCV000018154" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018154" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018154</a>
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<p>In the Leeward Islands of the Netherlands Antilles where the prevalence of hereditary hemorrhagic telangiectasia (HHT1; <a href="/entry/187300">187300</a>) is perhaps the highest of any geographic region, <a href="#11" class="mim-tip-reference" title="Gallione, C. J., Scheessele, E. A., Reinhardt, D., Duits, A. J., Berg, J. N., Westermann, C. J. J., Marchuk, D. A. <strong>Two common endoglin mutations in families with hereditary hemorrhagic telangiectasia in the Netherlands Antilles: evidence for a founder effect.</strong> Hum. Genet. 107: 40-44, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982033</a>] [<a href="https://doi.org/10.1007/s004390000326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982033">Gallione et al. (2000)</a> found that 1 of 2 common mutations was a missense mutation in exon 9a of the ENG gene: a G-to-T transversion at nucleotide 1238, resulting in a gly413-to-val substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10982033" 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">rs1554813783 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554813783;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=rs1554813783" 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=rs1554813783" 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=RCV000018155 OR RCV000521385 OR RCV001851484 OR RCV002367727" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018155, RCV000521385, RCV001851484, RCV002367727" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018155...</a>
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<p>In 7 of 10 families in the Netherlands Antilles with hereditary hemorrhagic telangiectasia (HHT1; <a href="/entry/187300">187300</a>), <a href="#11" class="mim-tip-reference" title="Gallione, C. J., Scheessele, E. A., Reinhardt, D., Duits, A. J., Berg, J. N., Westermann, C. J. J., Marchuk, D. A. <strong>Two common endoglin mutations in families with hereditary hemorrhagic telangiectasia in the Netherlands Antilles: evidence for a founder effect.</strong> Hum. Genet. 107: 40-44, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982033</a>] [<a href="https://doi.org/10.1007/s004390000326" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982033">Gallione et al. (2000)</a> found a splice site mutation in the ENG gene: a G-to-A transition at position +1 of intron 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10982033" 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 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121918402 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918402;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/rs121918402?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=rs121918402" 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=rs121918402" 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=RCV000018156 OR RCV001212827" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018156, RCV001212827" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018156...</a>
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<p>In 7 of 25 Danish families with hereditary hemorrhagic telangiectasia (HHT1; <a href="/entry/187300">187300</a>), <a href="#6" class="mim-tip-reference" title="Brusgaard, K., Kjeldsen, A. D., Poulsen, L., Moss, H., Vase, P., Rasmussen, K., Kruse, T. A., Horder, M. <strong>Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia.</strong> Clin. Genet. 66: 556-561, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15521985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15521985</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00341.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15521985">Brusgaard et al. (2004)</a> identified a 360C-A transversion in exon 3 of the ENG gene, resulting in a tyr120-to-ter (Y120X) substitution. <a href="#6" class="mim-tip-reference" title="Brusgaard, K., Kjeldsen, A. D., Poulsen, L., Moss, H., Vase, P., Rasmussen, K., Kruse, T. A., Horder, M. <strong>Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia.</strong> Clin. Genet. 66: 556-561, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15521985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15521985</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00341.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15521985">Brusgaard et al. (2004)</a> thought the Y120X founder mutation may have been introduced around 350 years earlier. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15521985" 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 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
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ENG, -142A-T, 5-PRIME UTR
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004794701" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004794701" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004794701</a>
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<p>In a 3-generation Spanish family with hereditary hemorrhagic telangiectasia (HHT1; <a href="/entry/187300">187300</a>), negative for mutation after screening with an HHT gene panel, <a href="#32" class="mim-tip-reference" title="Ruiz-Llorente, L., McDonald, J., Wooderchak-Donahue, W., Briggs, E., Chesnutt, M., Bayrak-Toydemir, P., Bernabeu, C. <strong>Characterization of a family mutation in the 5-prime untranslated region of the endoglin gene causative of hereditary hemorrhagic telangiectasia.</strong> J. Hum. Genet. 64: 333-339, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30728427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30728427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30728427[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/10.1038/s10038-019-0564-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30728427">Ruiz-Llorente et al. (2019)</a> sequenced the 5-prime UTR of the ENG gene and identified a heterozygous c.-142A-T transversion (c.-142A-T, NM_000118.3) in the 5-prime UTR, creating a putative AUG initiation codon at -141 bases from the constitutive translation initiation codon. The mutation segregated with disease in the family, and was not found in the dbSNP or gnomAD databases. Functional analysis in transiently transfected COS7 cells demonstrated a 60% reduction in expression with the mutant compared to control ENG. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30728427" 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>Variant Function</em></strong></p><p>
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<a href="#35" class="mim-tip-reference" title="Soukarieh, O., Tillet, E., Proust, C., Dupont, C., Jaspard-Vinassa, B., Soubrier, F., Goyenvalle, A., Eyries, M., Tregouet, D. A. <strong>uAUG creating variants in the 5-prime-UTR of ENG causing hereditary hemorrhagic telangiectasia.</strong> NPJ Genomic Med. 8: 32, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37848456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37848456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=37848456[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/10.1038/s41525-023-00378-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="37848456">Soukarieh et al. (2023)</a> performed functional analysis of the c.-142A-T ENG variant. They observed a dramatic reduction in steady-state protein levels with the variant in transfected HeLa cells, to less than 10% of wildtype levels, and RT-qPCR on RNA extracted from transfected cells confirmed the results. Western blot analysis of transduced human umbilical vein endothelial cells showed similar results, with mutant protein levels comparable to those obtained with the empty vector. Luciferase assay in HeLa cells showed a decrease in activity with the mutant compared to wildtype ENG, and in a BMP response-element assay, the mutant had 20% or less of wildtype activity. After suppression of the primary ATG of the ENG gene, the authors observed high mutant protein levels, almost twice those of the wildtype construct; the authors suggested that there might be competition beween the variant and wildtype AUGs at the translational level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37848456" 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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Abdalla, S. A., Letarte, M.
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<strong>Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease.</strong>
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J. Med. Genet. 43: 97-110, 2006.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15879500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15879500</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15879500[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=15879500" 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/10.1136/jmg.2005.030833" target="_blank">Full Text</a>]
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Abdalla, S. A., Pece-Barbara, N., Vera, S., Tapia, E., Paez, E., Bernabeu, C., Letarte, M.
|
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<strong>Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2.</strong>
|
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Hum. Molec. Genet. 9: 1227-1237, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10767348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10767348</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10767348" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/9.8.1227" target="_blank">Full Text</a>]
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Bayrak-Toydemir, P., McDonald, J., Markewitz, B., Lewin, S., Miller, F., Chou, L.-S., Gedge, F., Tang, W., Coon, H., Mao, R.
|
|
<strong>Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations.</strong>
|
|
Am. J. Med. Genet. 140A: 463-470, 2006.
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16470787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16470787</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16470787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.31101" target="_blank">Full Text</a>]
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Bellon, T., Corbi, A., Lastres, P., Cales, C., Cebrian, M., Vera, S., Cheifetz, S., Massague, J., Letarte, M., Bernabeu, C.
|
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<strong>Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions.</strong>
|
|
Europ. J. Immun. 23: 2340-2345, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8370410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8370410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8370410" 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/eji.1830230943" target="_blank">Full Text</a>]
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Bourdeau, A., Dumont, D. J., Letarte, M.
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<strong>A murine model of hereditary hemorrhagic telangiectasia.</strong>
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J. Clin. Invest. 104: 1343-1351, 1999.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10562296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10562296</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10562296[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=10562296" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI8088" target="_blank">Full Text</a>]
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Brusgaard, K., Kjeldsen, A. D., Poulsen, L., Moss, H., Vase, P., Rasmussen, K., Kruse, T. A., Horder, M.
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<strong>Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia.</strong>
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Clin. Genet. 66: 556-561, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15521985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15521985</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15521985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2004.00341.x" target="_blank">Full Text</a>]
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Chen, Y., Hao, Q., Kim, H., Su, H., Letarte, M., Karumanchi, S. A., Lawton, M. T., Barbaro, N. M., Yang, G.-Y., Young, W. L.
|
|
<strong>Soluble endoglin modulates aberrant cerebral vascular remodeling.</strong>
|
|
Ann. Neurol. 66: 19-27, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19670444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19670444</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19670444[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=19670444" 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/ana.21710" target="_blank">Full Text</a>]
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Cymerman, U., Vera, S., Karabegovic, A., Abdalla, S., Letarte, M.
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<strong>Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasia.</strong>
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Hum. Mutat. 21: 482-492, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12673790/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12673790</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12673790" 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.10203" target="_blank">Full Text</a>]
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Fernandez-Ruiz, E., St. Jacques, S., Bellon, T., Letarte, M., Bernabeu, C.
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<strong>Assignment of the human endoglin gene (END) to 9q34-qter.</strong>
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Cytogenet. Cell Genet. 64: 204-207, 1993.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8404038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8404038</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8404038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000133576" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Gallione1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gallione, C. J., Klaus, D. J., Yeh, E. Y., Stenzel, T. T., Xue, Y., Anthony, K. B., McAllister, K. A., Baldwin, M. A., Berg, J. N., Lux, A., Smith, J. D., Vary, C. P. H., Craigen, W. J., Westermann, C. J. J., Warner, M. L., Miller, Y. E., Jackson, C. E., Guttmacher, A. E., Marchuk, D. A.
|
|
<strong>Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.</strong>
|
|
Hum. Mutat. 11: 286-294, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554745" 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/(SICI)1098-1004(1998)11:4<286::AID-HUMU6>3.0.CO;2-B" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Gallione2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gallione, C. J., Scheessele, E. A., Reinhardt, D., Duits, A. J., Berg, J. N., Westermann, C. J. J., Marchuk, D. A.
|
|
<strong>Two common endoglin mutations in families with hereditary hemorrhagic telangiectasia in the Netherlands Antilles: evidence for a founder effect.</strong>
|
|
Hum. Genet. 107: 40-44, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982033</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10982033" 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/s004390000326" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Gougos1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gougos, A., Letarte, M.
|
|
<strong>Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells.</strong>
|
|
J. Biol. Chem. 265: 8361-8364, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1692830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1692830</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1692830" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Grisanti2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grisanti, S., Canbek, S., Kaiserling, E., Adam, A., Lafaut, B., Gelisken, F., Szurman, P., Henke-Fahle, S., Oficjalska-Mlynczak, J., Bartz-Schmidt, K. U.
|
|
<strong>Expression of endoglin in choroidal neovascularization.</strong>
|
|
Exp. Eye Res. 78: 207-213, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14729353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14729353</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14729353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.exer.2003.11.008" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Howe2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Howe, J. R., Haidle, J. L., Lal, G., Bair, J., Song, C., Pechman, B., Chinnathambi, S., Lynch, H. T.
|
|
<strong>ENG mutations in MADH4/BMPR1A mutation negative patients with juvenile polyposis. (Letter)</strong>
|
|
Clin. Genet. 71: 91-92, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17204053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17204053</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17204053" 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.1399-0004.2007.00734.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Kozak1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kozak, M.
|
|
<strong>Context effects and inefficient initiation at non-AUG codons in eucaryotic cell-free translation systems.</strong>
|
|
Molec. Cell. Biol. 9: 5073-5080, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2601709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2601709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2601709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/mcb.9.11.5073-5080.1989" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Lastella2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lastella, P., Sabba, C., Lenato, G. M., Resta, N., Lattanzi, W., Gallitelli, M., Cirulli, A., Guanti, G.
|
|
<strong>Endoglin gene mutations and polymorphisms in Italian patients with hereditary haemorrhagic telangiectasia.</strong>
|
|
Clin. Genet. 63: 536-540, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12786761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12786761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12786761" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2003.00081.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Lebrin2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lebrin, F., Goumans, M.-J., Jonker, L., Carvalho, R. L. C., Valdimarsdottir, G., Thorikay, M., Mummery, C., Arthur, H. M., ten Dijke, P.
|
|
<strong>Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction.</strong>
|
|
EMBO J. 23: 4018-4028, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15385967/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15385967</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15385967[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=15385967" 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/sj.emboj.7600386" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Lebrin2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lebrin, F., Srun, S., Raymond, K., Martin, S., van den Brink, S., Freitas, C., Breant, C., Mathivet, T., Larrivee, B., Thomas, J.-L., Arthur, H. M., Westermann, C. J. J., Disch, F., Mager, J. J., Snijder, R. J., Eichmann, A., Mummery, C. L.
|
|
<strong>Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia.</strong>
|
|
Nature Med. 16: 420-428, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20364125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20364125</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20364125" 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/nm.2131" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Lee2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, N. Y., Ray, B., How, T., Blobe, G. C.
|
|
<strong>Endoglin promotes transforming growth factor beta-mediated Smad 1/5/8 signaling and inhibits endothelial cell migration through its association with GIPC.</strong>
|
|
J. Biol. Chem. 283: 32527-32533, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18775991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18775991</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18775991[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=18775991" 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.M803059200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Lesca2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lesca, G., Plauchu, H., Coulet, F., Lefebvre, S., Plessis, G., Odent, S., Riviere, S., Leheup, B., Goizet, C., Carette, M.-F., Cordier, J.-F., Pinson, S., Soubrier, F., Calender, A., Giraud, S.
|
|
<strong>Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France.</strong>
|
|
Hum. Mutat. 23: 289-299, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15024723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15024723</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15024723" 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.20017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Li1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, D. Y., Sorensen, L. K., Brooke, B. S., Urness, L. D., Davis, E. C., Taylor, D. G., Boak, B. B., Wendel, D. P.
|
|
<strong>Defective angiogenesis in mice lacking endoglin.</strong>
|
|
Science 284: 1534-1537, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10348742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10348742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10348742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.284.5419.1534" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Lux2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lux, A., Gallione, C. J., Marchuk, D. A.
|
|
<strong>Expression analysis of endoglin missense and truncation mutations: insights into protein structure and disease mechanisms.</strong>
|
|
Hum. Molec. Genet. 9: 745-755, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10749981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10749981</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10749981" 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/9.5.745" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Marchuk2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marchuk, D. A., Srinivasan, S., Squire, T. L., Zawistowski, J. S.
|
|
<strong>Vascular morphogenesis: tales of two syndromes.</strong>
|
|
Hum. Molec. Genet. 12(R1): R97-R112, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12668602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12668602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12668602" 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/ddg103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="McAllister1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McAllister, K. A., Grogg, K. M., Johnson, D. W., Gallione, C. J., Baldwin, M. A., Jackson, C. E., Helmbold, E. A., Markel, D. S., McKinnon, W. C., Murrell, J., McCormick, M. K., Pericak-Vance, M. A., Heutink, P., Oostra, B. A., Haitjema, T., Westerman, C. J. J., Porteous, M. E., Guttmacher, A. E., Letarte, M., Marchuk, D. A.
|
|
<strong>Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.</strong>
|
|
Nature Genet. 8: 345-351, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7894484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7894484</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7894484" 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/ng1294-345" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Muenzner2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muenzner, P., Bachmann, V., Zimmermann, W., Hentschel, J., Hauck, C. R.
|
|
<strong>Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation.</strong>
|
|
Science 329: 1197-1201, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20813953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20813953</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20813953" 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/10.1126/science.1190892" 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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|
|
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|
|
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|
|
Paquet, M.-E., Pece-Barbara, N., Vera, S., Cymerman, U., Karabegovic, A., Shovlin, C., Letarte, M.
|
|
<strong>Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function.</strong>
|
|
Hum. Molec. Genet. 10: 1347-1357, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11440987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11440987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11440987" 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/10.13.1347" 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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|
Pece, N., Vera, S., Cymerman, U., White, R. I., Jr., Wrana, J. L., Letarte, M.
|
|
<strong>Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative.</strong>
|
|
J. Clin. Invest. 100: 2568-2579, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9366572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9366572</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9366572" 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/JCI119800" target="_blank">Full Text</a>]
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|
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|
|
|
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|
|
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|
|
<a id="Pece-Barbara1999" class="mim-anchor"></a>
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|
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|
|
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|
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Pece-Barbara, N., Cymerman, U., Vera, S., Marchuk, D. A., Letarte, M.
|
|
<strong>Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1.</strong>
|
|
Hum. Molec. Genet. 8: 2171-2181, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10545596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10545596</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10545596" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/8.12.2171" target="_blank">Full Text</a>]
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|
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|
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<a id="29" class="mim-anchor"></a>
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|
|
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|
|
<p class="mim-text-font">
|
|
Pilz, A., Woodward, K., Peters, J., Povey, S., Abbott, C.
|
|
<strong>Comparative mapping of 38 human chromosome 9 loci in the laboratory mouse. (Abstract)</strong>
|
|
Ann. Hum. Genet. 58: 231-232, 1994.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
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|
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<a id="Qureshi1995" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Qureshi, S. T., Gros, P., Letarte, M., Malo, D.
|
|
<strong>The murine endoglin gene (Eng) maps to chromosome 2.</strong>
|
|
Genomics 26: 165-166, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7782079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7782079</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7782079" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0888-7543(95)80099-8" 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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|
|
Rius, C., Smith, J. D., Almendro, N., Langa, C., Botella, L. M., Marchuk, D. A., Vary, C. P. H., Bernabeu, C.
|
|
<strong>Cloning of the promoter region of human endoglin, the target gene for hereditary hemorrhagic telangiectasia type 1.</strong>
|
|
Blood 92: 4677-4690, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9845534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9845534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9845534" 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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|
|
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|
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|
|
Ruiz-Llorente, L., McDonald, J., Wooderchak-Donahue, W., Briggs, E., Chesnutt, M., Bayrak-Toydemir, P., Bernabeu, C.
|
|
<strong>Characterization of a family mutation in the 5-prime untranslated region of the endoglin gene causative of hereditary hemorrhagic telangiectasia.</strong>
|
|
J. Hum. Genet. 64: 333-339, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30728427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30728427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30728427[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=30728427" 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/10.1038/s10038-019-0564-x" 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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Shoukier, M., Teske, U., Weise, A., Engel, W., Argyriou, L.
|
|
<strong>Characterization of five novel large deletions causing hereditary haemorrhagic telangiectasia.</strong>
|
|
Clin. Genet. 73: 320-330, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18312453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18312453</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18312453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2008.00968.x" 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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|
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|
|
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|
|
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|
|
Shovlin, C. L., Hughes, J. M. B., Scott, J., Seidman, C. E., Seidman, J. G.
|
|
<strong>Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia.</strong>
|
|
Am. J. Hum. Genet. 61: 68-79, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9245986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9245986</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9245986" 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/10.1086/513906" 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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|
|
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|
|
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Soukarieh, O., Tillet, E., Proust, C., Dupont, C., Jaspard-Vinassa, B., Soubrier, F., Goyenvalle, A., Eyries, M., Tregouet, D. A.
|
|
<strong>uAUG creating variants in the 5-prime-UTR of ENG causing hereditary hemorrhagic telangiectasia.</strong>
|
|
NPJ Genomic Med. 8: 32, 2023.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37848456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37848456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=37848456[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=37848456" 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/s41525-023-00378-5" 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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|
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|
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<a id="Sweet2005" class="mim-anchor"></a>
|
|
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|
|
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|
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Sweet, K., Willis, J., Zhou, X.-P., Gallione, C., Sawada, T., Alhopuro, P., Khoo, S. K., Patocs, A., Martin, C., Bridgeman, S., Heinz, J., Pilarski, R., Lehtonen, R., Prior, T. W., Frebourg, T., Teh, B. T., Marchuk, D. A., Aaltonen, L. A., Eng, C.
|
|
<strong>Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.</strong>
|
|
JAMA 294: 2465-2473, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16287957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16287957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16287957" 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/10.1001/jama.294.19.2465" target="_blank">Full Text</a>]
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Wang, X., Abraham, S., McKenzie, J. A. G., Jeffs, N., Swire, M., Tripathi, V. B., Luhmann, U. F. O., Lange, C. A. K., Zhai, Z., Arthur, H. M., Bainbridge, J. W. B., Moss, S. E., Greenwood, J.
|
|
<strong>LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling.</strong>
|
|
Nature 499: 306-311, 2013. Note: Erratum: Nature 501: 578 only, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23868260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23868260</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23868260[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=23868260" 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/nature12345" target="_blank">Full Text</a>]
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Wehner, L.-E., Folz, B. J., Argyriou, L., Twelkemeyer, S., Teske, U., Geisthoff, U. W., Werner, J. A., Engel, W., Nayernia, K.
|
|
<strong>Mutation analysis in hereditary haemorrhagic telangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1 mutations.</strong>
|
|
Clin. Genet. 69: 239-245, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16542389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16542389</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16542389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2006.00574.x" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 11/18/2024
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<span class="mim-text-font">
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Ada Hamosh - updated : 9/20/2013<br>Cassandra L. Kniffin - updated : 1/25/2011<br>Ada Hamosh - updated : 10/27/2010<br>Cassandra L. Kniffin - updated : 5/27/2010<br>Patricia A. Hartz - updated : 4/21/2009<br>Cassandra L. Kniffin - updated : 9/16/2008<br>Marla J. F. O'Neill - updated : 3/9/2007<br>Cassandra L. Kniffin - updated : 4/27/2006<br>Cassandra L. Kniffin - updated : 3/21/2006<br>Victor A. McKusick - updated : 3/9/2006<br>Patricia A. Hartz - updated : 7/6/2005<br>Victor A. McKusick - updated : 3/31/2005<br>George E. Tiller - updated : 3/3/2005<br>Jane Kelly - updated : 7/30/2004<br>Victor A. McKusick - updated : 5/5/2004<br>Victor A. McKusick - updated : 7/10/2003<br>Victor A. McKusick - updated : 6/11/2003<br>George E. Tiller - updated : 11/13/2001<br>Paul J. Converse - updated : 8/17/2001<br>Victor A. McKusick - updated : 9/12/2000<br>George E. Tiller - updated : 7/7/2000<br>George E. Tiller - updated : 4/25/2000<br>Victor A. McKusick - updated : 12/7/1999<br>Victor A. McKusick - updated : 11/19/1999<br>Ada Hamosh - updated : 5/27/1999<br>Victor A. McKusick - updated : 2/1/1999<br>Victor A. McKusick - updated : 4/29/1998<br>Victor A. McKusick - updated : 12/3/1997<br>Victor A. McKusick - updated : 8/20/1997<br>Alan F. Scott - updated : 9/26/1995
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Victor A. McKusick : 11/3/1993
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alopez : 11/18/2024
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carol : 08/22/2019<br>carol : 11/22/2017<br>carol : 06/26/2015<br>alopez : 10/28/2013<br>alopez : 9/20/2013<br>carol : 9/16/2013<br>wwang : 2/17/2011<br>ckniffin : 1/25/2011<br>alopez : 10/27/2010<br>wwang : 6/15/2010<br>ckniffin : 5/27/2010<br>mgross : 4/24/2009<br>terry : 4/21/2009<br>wwang : 9/24/2008<br>ckniffin : 9/16/2008<br>wwang : 3/13/2007<br>terry : 3/9/2007<br>wwang : 5/3/2006<br>ckniffin : 4/27/2006<br>wwang : 3/23/2006<br>ckniffin : 3/21/2006<br>terry : 3/9/2006<br>mgross : 7/7/2005<br>terry : 7/6/2005<br>wwang : 4/6/2005<br>wwang : 4/1/2005<br>terry : 3/31/2005<br>alopez : 3/3/2005<br>tkritzer : 8/4/2004<br>terry : 7/30/2004<br>tkritzer : 6/1/2004<br>terry : 5/5/2004<br>carol : 4/29/2004<br>ckniffin : 4/12/2004<br>terry : 3/30/2004<br>carol : 7/11/2003<br>terry : 7/10/2003<br>tkritzer : 6/27/2003<br>tkritzer : 6/24/2003<br>terry : 6/11/2003<br>cwells : 11/20/2001<br>cwells : 11/13/2001<br>mgross : 8/17/2001<br>carol : 9/14/2000<br>terry : 9/12/2000<br>alopez : 7/10/2000<br>alopez : 7/7/2000<br>alopez : 4/25/2000<br>mcapotos : 12/9/1999<br>terry : 12/7/1999<br>alopez : 12/2/1999<br>terry : 11/19/1999<br>alopez : 5/27/1999<br>carol : 2/3/1999<br>terry : 2/1/1999<br>dkim : 9/11/1998<br>terry : 5/29/1998<br>dholmes : 5/12/1998<br>carol : 5/8/1998<br>terry : 4/29/1998<br>mark : 12/5/1997<br>terry : 12/3/1997<br>jenny : 8/22/1997<br>terry : 8/20/1997<br>mark : 5/29/1996<br>terry : 3/2/1995<br>carol : 12/22/1994<br>pfoster : 5/9/1994<br>carol : 11/17/1993<br>carol : 11/3/1993
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<span class="mim-font">
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<strong>*</strong> 131195
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ENDOGLIN; ENG
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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CD105
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ENG</em></strong>
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Cytogenetic location: 9q34.11
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Genomic coordinates <span class="small">(GRCh38)</span> : 9:127,815,016-127,854,658 </span>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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9q34.11
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Telangiectasia, hereditary hemorrhagic, type 1
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187300
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Autosomal dominant
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>Endoglin (ENG), also called CD105, is a homodimeric membrane glycoprotein primarily associated with human vascular endothelium. It is also found on bone marrow proerythroblasts, activated monocytes, and lymphoblasts in childhood leukemia. Endoglin is a component of the transforming growth factor-beta (TGFB) receptor complex and binds TGFB1 (190180) with high affinity (Rius et al., 1998). </p>
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<strong>Cloning and Expression</strong>
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<p>Gougos and Letarte (1990) isolated a cDNA encoding ENG lacking a leader sequence from an endothelial cell cDNA library. By screening a leukemia cell cDNA library, Bellon et al. (1993) obtained full-length cDNAs encoding 2 variants of ENG. Both contain a 25-amino acid leader peptide, followed by 561 residues in the extracellular portion and a 25-amino acid transmembrane sequence. However, the long variant has a 47-amino acid cytoplasmic tail, while the tail of the short variant contains only 14 residues. Flow cytometric and immunoprecipitation analyses indicated high expression of both the 160- and 170-kD disulfide-linked homodimer ENG variants at the cell surface. RT-PCR analysis detected expression of both variants on activated monocytes, endothelial cells, and placenta, with the long form being predominant. </p>
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<strong>Gene Structure</strong>
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<p>McAllister et al. (1994) concluded that the coding region of the ENG gene contains 14 exons. They thought it likely that there are additional exons. </p>
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<strong>Mapping</strong>
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<p>By Southern blot analysis of DNA from human-hamster somatic cell hybrids, Fernandez-Ruiz et al. (1993) mapped the ENG gene to human chromosome 9. By fluorescence in situ hybridization, they regionalized the assignment to 9q34-qter, distal to the breakpoint of the Philadelphia chromosome. The mouse endoglin locus is genetically inseparable from the adenylate kinase-1 locus (Pilz et al., 1994). Thus, the ENG gene is probably located in the 9q34.1 region in the human. Qureshi et al. (1995) mapped the mouse ENG homolog to chromosome 2, near the nebulin locus (161650). </p>
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<strong>Gene Function</strong>
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<p>Bellon et al. (1993) found that both isoforms of ENG could bind TGFB1. </p><p>Rius et al. (1998) cloned and characterized the promoter region of the ENG gene. They showed that the endoglin promoter exhibits inducibility in the presence of TGFB1, suggesting possible therapeutic treatments in HHT1 (187300) patients, in which the expression level of the normal endoglin allele might not reach the threshold required for its function. </p><p>Grisanti et al. (2004) analyzed endoglin expression in choroidal neovascular membranes (CNVMs) surgically excised from eyes with age-related macular degeneration (ARMD; see 153800). Endoglin expression was increased in the endothelial cells of CNVMs but was rarely associated with a concomitant expression of the proliferation marker Ki-67 (176741). The authors concluded that the elevated expression of endoglin in the surgically excised CNVMs suggested a persisting postmitotic activation in an advanced stage of neovascular tissue. </p><p>Hereditary hemorrhagic telangiectasia (see 187300) and cerebral cavernous malformations (see 116860) are disorders involving disruption of normal vascular morphogenesis. The autosomal dominant mode of inheritance in both of these disorders suggested to Marchuk et al. (2003) that their underlying genes might regulate critical aspects of vascular morphogenesis. The authors summarized the roles of these genes, endoglin, KRIT1 (604214), and ALK1 (ACVRL1; 601284), in the genetic control of angiogenesis. </p><p>Lebrin et al. (2004) found that mouse endothelial cells lacking endoglin did not grow because Tgfb/Alk1 signaling was reduced and Tgfb/Alk5 (190181) signaling was increased. Surviving cells adapted to the imbalance and proliferated by downregulating Alk5 expression. Lebrin et al. (2004) concluded that endoglin has a role in the balance of ALK1 and ALK5 signaling to regulate endothelial cell proliferation. </p><p>GIPC1 (605072) is a scaffolding protein that regulates cell surface receptor expression and trafficking. Using predominantly embryonic mouse endothelial cell lines, Lee et al. (2008) showed that endoglin and Gipc interacted directly. The interaction enhanced TGF-beta-1-induced phosphorylation of Smad1 (601595)/Smad5 (603110)/Smad8 (SMAD9; 603295), increased a Smad1/Smad5/Smad8-responsive promoter, and inhibited endothelial cell migration. </p><p>Chen et al. (2009) found increased levels of soluble endoglin in vascular surgical specimens from 33 patients with arteriovenous malformations of the brain (BAVM; 108010) compared to similar specimens from 8 epileptic patients. However, there was no difference in expression of membrane-bound endoglin and no difference in plasma soluble endoglin between BAVM patients and controls. Transduction of soluble endoglin in mouse brain resulted in the formation of abnormal and dysplastic capillary structures, and was associated with increased levels of matrix metalloproteinase activity and oxidative radicals. Chen et al. (2009) suggested that soluble endoglin may play a role in the formation of sporadic BAVM by acting as a decoy receptor, resulting in inhibition of TGF-beta signaling and functional haploinsufficiency of ENG, as observed in patients with HHT1. </p><p>Muenzner et al. (2010) found that CEA (114890)-binding bacteria colonized the urogenital tract of CEA transgenic mice, but not of wildtype mice, by suppressing exfoliation of mucosal cells. CEA binding triggered de novo expression of the transforming growth factor receptor CD105, changing focal adhesion composition and activating beta-1 integrins (135630). Muenzner et al. (2010) concluded that this manipulation of integrin inside-out signaling promotes efficient mucosal colonization and represents a potential target to prevent or cure bacterial infections. </p><p>Wang et al. (2013) identified upregulation of Lrg1 (611289) in the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology. The authors showed that in the presence of transforming growth factor-beta-1 (TGFB1; 190180), Lrg1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 developed a mild retinal vascular phenotype but exhibited a significant reduction in pathologic ocular angiogenesis. Lrg1 bound directly to the Tgf-beta accessory receptor endoglin, which, in the presence of TGF-beta-1, resulted in promotion of the proangiogenic Smad1/5/8 signaling pathway. Lrg1 antibody blockade inhibited this switch and attenuated angiogenesis. Wang et al. (2013) concluded that these studies revealed that LRG1 is a regulator of angiogenesis that mediates its effect by modulating TGF-beta signaling. </p>
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<strong>Molecular Genetics</strong>
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<p>In a panel of 68 DNA samples from probands of unrelated hereditary hemorrhagic telangiectasia (see HHT1; 187300) families, most of whom were members of kindreds with pulmonary arteriovenous malformations (PAVMs), McAllister et al. (1994) identified mutations in the ENG gene in 3 affected individuals. </p><p>Shovlin et al. (1997) identified 7 novel mutations in the ENG gene in 8 families. Two of the mutations (a termination codon in exon 4 and a large genomic deletion extending 3-prime of intron 8) did not produce a stable ENG transcript in lymphocytes. Five other mutations (2 donor splice site mutations (e.g., 131195.0004) and 3 deletions) produced altered mRNAs that were predicted to encode markedly truncated ENG proteins. These data suggested that the molecular mechanism by which ENG mutations cause HHT is haploinsufficiency. Furthermore, because the clinical manifestation of disease in these 8 families was similar, Shovlin et al. (1997) hypothesized that phenotypic variation of HHT is not related to a particular ENG mutation. They found that 41% (23 of 56) of HHT patients with ENG mutations had pulmonary arteriovenous malformations, whereas a significantly smaller fraction, 14% (5 of 35), of HHT patients in whom linkage analyses indicated non-ENG mutations had PAVMs (P less than 0.01). </p><p>In a newborn from a family with HHT, Pece et al. (1997) identified a novel endoglin splice site mutation (131195.0005) that resulted in skipping of exon 3 and the expression of a mutant protein missing 47 amino acids but with an intact transmembrane region. This mutant protein was considered particularly suited for testing the dominant-negative model as it is more likely to be expressed at the cell surface than truncated ones. However, it was detectable only by metabolic labeling, did not form heterodimers with normal endoglin, and did not reach the cell surface. In activated monocytes from 3 patients with known truncations, no mutant protein could be detected. However, when cDNA corresponding to 2 other HHT1 endoglin truncations were overexpressed in COS-1 cells, mutant proteins could be detected intracellularly, were not secreted, and did not form heterodimers with wildtype endoglin. Thus, Pece et al. (1997) concluded that mutant endoglin in HHT patients appears to be only transiently expressed and not to represent a dominant negative. The data strongly suggested that a reduced level of functional endoglin leads to the abnormalities seen in HHT1 patients. In these studies, expression of normal and mutant endoglin proteins was analyzed in umbilical vein endothelial cells from the baby and in activated monocytes from the affected father. In both samples, only normal dimeric endoglin (160 kD) was observed at the cell surface, at 50% of control levels. Despite an intact transmembrane region, mutant protein was detectable only by metabolic labeling, as an intracellular homodimer of 130 kD. </p><p>Gallione et al. (1998) described 11 novel ENG mutations in HHT kindreds, which included missense and splice site mutations. In 2 unrelated families, they identified a T-to-C transition in the ATG initiation codon, which converted the initiator methionine to threonine. Non-ATG codons can initiate at 3 to 5% of normal translation levels when flanked by specific consensus sequences (Kozak, 1989). However, the sequence context of the specific mutation in the 2 HHT families did not fit the consensus for even such reduced initiation. The first potential in-frame initiation codon was within exon 5. If protein synthesis was initiated at this position, the product would lack the signal peptide for proper membrane trafficking, as well as 30% of the N-terminal residues. This initiation codon mutation appeared to be a classic null allele that eliminated the translation of the endoglin protein. </p><p>Pece-Barbara et al. (1999) stated that to that date 29 different mutations had been reported in HHT1 in the endoglin gene and 18 distinct mutations had been described for the ALK1 gene (601284), which underlies type 2 hereditary hemorrhagic telangiectasia (HHT2; 600376). </p><p>Although a dominant-negative model of endoglin dysfunction was initially proposed for HHT1, Pece et al. (1997) observed a mutant protein (131195.0005) that was transiently expressed intracellularly both in monocytes from an HHT1 patient and in human umbilical vein endothelial cells (HUVECs) from the child of the patient. As the cell surface-expressed protein was still able to associate with the TGF-beta receptor complex, this indicated that it is the reduction in the level of surface endoglin, rather than interference by mutant protein, that is involved in the generation of HHT1. The description of 3 null mutations where mRNA transcripts were undetectable again suggested that endoglin haploinsufficiency is the molecular basis for HHT1. The observation that every HHT1 family so far studied was found to have a distinct mutation and that mutations of all types are distributed throughout the gene was again consistent with a haploinsufficiency model. Pece-Barbara et al. (1999) studied 4 missense mutations and found that none was significantly expressed at the surface of COS-1 transfectants. Thus, although these 4 HHT1 missense mutations led to transient intracellular species, they cannot interfere with normal endoglin function. </p><p>To determine whether mechanisms other than haploinsufficiency might be involved in HHT1, Lux et al. (2000) investigated 8 different mutations in the ENG gene. Missense mutants were expressed but apparently misfolded, and most showed no cell surface expression. When coexpressed with wildtype endoglin, missense mutants were able to dimerize with normal endoglin protein and were transported to the cell surface. The protein product of one truncation mutation was unable to dimerize with normal endoglin, and likely acts through haploinsufficiency. On the contrary, the delta-GC frameshift mutation (131195.0003) was able to dimerize with normal endoglin, and likely acts in a dominant-negative fashion by interfering with protein processing or cell surface expression. Thus, the authors concluded that either dominant-negative protein interactions or haploinsufficiency can cause HHT1. </p><p>To maximize the detection of potential mutant proteins, Paquet et al. (2001) utilized pulse-chase experiments to analyze the expression of large truncation mutations and missense mutations in cells from HHT1 patients with 13 unique mutations. All HHT1 mutants analyzed, although expressed to various degrees in COS-1 cells, were either undetectable, present at low levels as transient intracellular forms, or expressed as partially glycosylated precursors in endogenous cells. The mutants did not form heterodimers with normal endoglin and did not interfere with its normal trafficking to the cell surface, further supporting the haploinsufficiency model. </p><p>In COS-1 transfected cells, Abdalla et al. (2000) determined that ALK1 was found in the TGFB1 and -B3 (190230) receptor complexes in association with endoglin and TGFBR2 (190182), but not in activin (see 147290) receptor complexes containing endoglin. In HUVEC, ALK1 was not detectable in TGFB1 or -B3 receptor complexes. However, in the absence of ligand, ALK1 and endoglin interactions were observed by immunoprecipitation/Western blot in HUVEC from normal as well as HHT1 and HHT2 patients. The authors hypothesized that a transient association between ALK1 and endoglin is required at a critical level to ensure vessel wall integrity. </p><p>Cymerman et al. (2003) optimized a quantitative multiplex PCR (QMPCR) analysis to efficiently detect deletions and insertions in the ENG gene in HHT1 patients from 18 families. They reported 17 novel mutations, of which 6 were detected by QMPCR. Review of 80 HHT1 families (62 previously reported and the 18 described) indicated that 10% would not have been resolved by sequencing and that an additional 25% could be revealed by QMPCR performed before sequencing. Thus the use of QMPCR can accelerate genetic screening for HHT1 and resolve mutations affecting whole exons. </p><p>Lastella et al. (2003) detected 4 novel and 1 previously reported mutation in the ENG gene in Italian patients with HHT. </p><p>In 160 unrelated cases of HHT, Lesca et al. (2004) screened the coding sequences of the ENG and ALK1 genes. Germline mutations were identified in 100 patients (62.5%): 36 of the mutations were in ENG and 64 were in ALK1. </p><p>In 7 Danish HHT families, Brusgaard et al. (2004) identified a novel nonsense mutation (131195.0009) in the ENG gene, which they characterized as a founder mutation. </p><p>Abdalla and Letarte (2006) tabulated the known ENG mutations identified in hereditary hemorrhagic telangiectasia. </p><p>Bayrak-Toydemir et al. (2006) identified mutations in 26 (76%) of 34 kindreds with HHT. Fourteen (54%) mutations were in the ENG gene, consistent with HHT1, and 12 (46%) were in the ACVRL1 gene, consistent with HHT2. </p><p>Wehner et al. (2006) identified mutations in 32 (62.7%) of 51 unrelated German patients with HHT. Among these mutations, 11 of 13 ENG mutations and 12 of 17 ACVRL1 mutations were not previously reported in the literature. Analysis of genotype/phenotype correlations was consistent with a more common frequency of PAVMs in patients with ENG mutations (HHT1). </p><p>Sweet et al. (2005) sequenced the ENG gene in 14 patients with juvenile polyposis syndrome (JPS; 174900) who were negative for mutation in the 2 known JPS genes, SMAD4 (600993) and BMPR1A (601299), and identified germline missense mutations in the ENG gene in 2 patients, respectively. The mutations were not found in 105 North American controls. In 3 of 31 patients with JPS who were negative for mutations in the SMAD4 and BMPR1A genes, Howe et al. (2007) identified 2 different nonsynonymous substitutions that had been previously identified as polymorphisms in patients with HTT. Howe et al. (2007) stated that their findings did not confirm the suggestion that the ENG gene predisposes for JPS. </p><p>In a German woman with clinical features of HHT and negative direct sequencing results, Shoukier et al. (2008) identified a deletion of exon 4 of the ENG gene using quantitative real-time polymerase chain reaction (qRT-PCR) and confirmed by multiplex ligation-dependent probe amplification (MLPA). </p><p>In a 3-generation Spanish family with HHT that was negative for mutation after screening with an HHT gene panel, Ruiz-Llorente et al. (2019) sequenced the 5-prime UTR of the ENG gene and identified a variant (c.-142A-T; 131195.0010) that creates a putative AUG initiation codon at -141 bases from the constitutive translation initiation codon. Functional analysis demonstrated markedly reduced expression with the mutant compared to control ENG. </p><p>From a cohort of 274 sequenced patients with genetically unresolved HHT, Soukarieh et al. (2023) identified 2 patients with mutations in the 5-prime UTR of the ENG gene, c.-79C-T and c.-68G-A, which were confirmed by Sanger sequencing. Functional analysis of these 2 variants as well as 3 additional previously published 5-prime UTR ENG variants identified in HHT patients, including the c.142A-T mutation, revealed that all 5 variants created upstream AUGs at the origin of upstream overlapping open reading frames (uoORFs) ending at the same stop codon (c.125), and all showed altered protein levels and function. Experiments using constructs in which the canonical start site had been deleted revealed that the identified upstream AUGs could initiate translation, suggesting that the associated effects were translation-dependent. The authors noted that all of the uoORF-creating variants studied showed ENG protein levels and BMP response element (BRE) activity that were less than 40% and 50%, respectively, compared to wildtype ENG, and were associated with severe HHT symptoms. </p>
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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>Li et al. (1999) generated mice deficient for endoglin using homologous recombination. Eng +/- mice had normal life expectancy, fertility, and gross appearance. Eng -/- mice died by embryonic day 11.5. At embryonic day 10.5, Eng -/- mice were 3 times smaller than Eng +/+ mice and had fewer somites. The Eng -/- embryos exhibited an absence of vascular organization and the presence of multiple pockets of red blood cells on the surface of the yolk sac. Epithelial marker expression was not disrupted in Eng -/- mice. There was persistence of an immature perineural vascular plexus, indicating a failure of endothelial remodeling in Eng -/- embryos. At embryonic day 10.5, the cardiac tube did not complete rotation and was associated with a serosanguinous pericardial effusion. By embryonic day 10.5, the major vessels including the dorsal aortae, intersomitic vessels, branchial arches, and carotid arteries were atretic and disorganized in Eng -/- embryos. There was also poor vascular smooth muscle cell formation at both embryonic days 9.5 and 10.5. These vascular smooth muscle cell abnormalities preceded the differences in endothelial organization. In contrast to mice lacking TGF-beta, vasculogenesis was unaffected. Li et al. (1999) concluded that their results demonstrated that endoglin is essential for angiogenesis and suggest a pathogenic mechanism for HHT1. </p><p>Bourdeau et al. (1999) likewise generated mice lacking 1 or both copies of the endoglin gene. Endoglin null embryos died at gestational day 10.0-10.5 due to defects in vessel and heart development. Vessel formation appeared normal until hemorrhage occurred in yolk sacs and embryos. The primitive vascular plexus of the yolk sac failed to mature into defined vessels, and vascular channels dilated and ruptured. Internal bleeding was seen in the peritoneal cavity, implying fragile vessels. Heart development was arrested at day 9.0, and the atrioventricular canal endocardium failed to undergo mesenchymal transformation and cushion-tissue formation. The data suggested that endoglin is critical for both angiogenesis and heart valve formation. Some heterozygotes showed signs of HHT, such as telangiectases or recurrent nosebleeds. In this murine model of HHT, it appeared that epigenetic factors and modifier genes, some of which are present in the 129/Ola strain, which shows expressing heterozygotes, contribute to disease heterogeneity. </p><p>Lebrin et al. (2010) showed that treatment of Eng +/- with thalidomide normalized inappropriate vessel formation and promoted pericyte and mural cell activation and vessel maturation via increased expression of Pdgfb (190040). In vitro studies of mouse tissue showed that thalidomide stimulated the recruitment of mural cells to the vessel branches, resulting in a stabilization of blood vessels and a rescue of vessel wall defects. Treatment reduced nosebleed frequency in 6 of 7 humans with HHT, and reduced the duration of nosebleeds in 3 of 4 for whom data were available. </p>
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</span>
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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>10 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 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ENG, TYR277TER
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<br />
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SNP: rs121918400,
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gnomAD: rs121918400,
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ClinVar: RCV000018148, RCV003593860
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with hereditary hemorrhagic telangiectasia (HHT1; 187300), McAllister et al. (1994) found a C-to-G transition at nucleotide position 831 in the ENG gene, resulting in conversion of tyrosine-277 to a termination codon. The truncated protein resulting from this mutation would comprise only half of the extracellular domain and lack the membrane-spanning and cytoplasmic domains. </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 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ENG, 39-BP DEL, NT882
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<br />
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SNP: rs2131886961,
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ClinVar: RCV000018149
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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 affected members of a family with hereditary hemorrhagic telangiectasia (HHT1; 187300), McAllister et al. (1994) found deletion of 39 nucleotides (882 to 920) in exon 7 of the ENG gene, removing 13 amino acids from the protein and altering the first amino acid (position 307) in a potential N-linked glycosylation site. The mutation segregated only with affected members of the 3-generation family. </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 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ENG, 2-BP DEL, NT1153
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<br />
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SNP: rs2131875838,
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ClinVar: RCV000018150, RCV003593861, RCV004791227
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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 affected members of a family with hereditary hemorrhagic telangiectasia (HHT1; 187300), McAllister et al. (1994) found a 2-bp deletion (nucleotides 1553 and 1554) in exon 11 of the ENG gene that created a MaeIII restriction site and caused a frameshift with a premature termination after an additional 7 amino acids. The predicted truncated protein would lack the membrane-spanning and cytoplasmic domains of endoglin. </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 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ENG, IVS3DS, A-G, +4
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<br />
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SNP: rs1564457752,
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ClinVar: RCV000018151, RCV001851903, RCV004018638, RCV004700247
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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>One of 7 novel mutations in the ENG gene found by Shovlin et al. (1997) in patients with hereditary hemorrhagic telangiectasia-1 (HHT1; 187300) was a deletion of exon 3 due to an A-to-G transition at position 4 of the donor splice site of intron 3. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ENG, IVS3DS, G-A, +1
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<br />
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SNP: rs886039505,
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ClinVar: RCV000255227, RCV000274164, RCV001034674, RCV002450790
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a patient with hereditary hemorrhagic telangiectasia-1 (HHT1; 187300), Pece et al. (1997) detected a splice site mutation of the ENG gene, resulting in in-frame deletion of exon 3 from the transcript and a truncated polypeptide. </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>.0006 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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|
ENG, MET1THR
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<br />
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SNP: rs267606783,
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ClinVar: RCV000018153, RCV002433460
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In 2 unrelated families with hereditary hemorrhagic telangiectasia-1 (HHT1; 187300), Gallione et al. (1998) identified a missense mutation of the initiation codon of the ENG gene. A T-to-C transition converted ATG (met) to ACG (thr). Since flanking sequences did not satisfy the consensus sequences found by Kozak (1989) to permit initiation from non-ATG codons and the first potential in-frame initiation codon was within exon 5, Gallione et al. (1998) predicted that this would function as a classic null mutation. </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>.0007 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
ENG, GLY413VAL
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<br />
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|
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SNP: rs121918401,
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|
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gnomAD: rs121918401,
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|
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ClinVar: RCV000018154
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In the Leeward Islands of the Netherlands Antilles where the prevalence of hereditary hemorrhagic telangiectasia (HHT1; 187300) is perhaps the highest of any geographic region, Gallione et al. (2000) found that 1 of 2 common mutations was a missense mutation in exon 9a of the ENG gene: a G-to-T transversion at nucleotide 1238, resulting in a gly413-to-val 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>
|
|
<span class="mim-font">
|
|
<strong>.0008 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
|
|
</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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ENG, IVS1DS, G-A, +1
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<br />
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SNP: rs1554813783,
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ClinVar: RCV000018155, RCV000521385, RCV001851484, RCV002367727
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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 7 of 10 families in the Netherlands Antilles with hereditary hemorrhagic telangiectasia (HHT1; 187300), Gallione et al. (2000) found a splice site mutation in the ENG gene: a G-to-A transition at position +1 of intron 1. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0009 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
|
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ENG, TYR120TER
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<br />
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SNP: rs121918402,
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gnomAD: rs121918402,
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ClinVar: RCV000018156, RCV001212827
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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 7 of 25 Danish families with hereditary hemorrhagic telangiectasia (HHT1; 187300), Brusgaard et al. (2004) identified a 360C-A transversion in exon 3 of the ENG gene, resulting in a tyr120-to-ter (Y120X) substitution. Brusgaard et al. (2004) thought the Y120X founder mutation may have been introduced around 350 years earlier. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0010 HEREDITARY HEMORRHAGIC TELANGIECTASIA 1</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ENG, -142A-T, 5-PRIME UTR
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<br />
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ClinVar: RCV004794701
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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 3-generation Spanish family with hereditary hemorrhagic telangiectasia (HHT1; 187300), negative for mutation after screening with an HHT gene panel, Ruiz-Llorente et al. (2019) sequenced the 5-prime UTR of the ENG gene and identified a heterozygous c.-142A-T transversion (c.-142A-T, NM_000118.3) in the 5-prime UTR, creating a putative AUG initiation codon at -141 bases from the constitutive translation initiation codon. The mutation segregated with disease in the family, and was not found in the dbSNP or gnomAD databases. Functional analysis in transiently transfected COS7 cells demonstrated a 60% reduction in expression with the mutant compared to control ENG. </p><p><strong><em>Variant Function</em></strong></p><p>
|
|
Soukarieh et al. (2023) performed functional analysis of the c.-142A-T ENG variant. They observed a dramatic reduction in steady-state protein levels with the variant in transfected HeLa cells, to less than 10% of wildtype levels, and RT-qPCR on RNA extracted from transfected cells confirmed the results. Western blot analysis of transduced human umbilical vein endothelial cells showed similar results, with mutant protein levels comparable to those obtained with the empty vector. Luciferase assay in HeLa cells showed a decrease in activity with the mutant compared to wildtype ENG, and in a BMP response-element assay, the mutant had 20% or less of wildtype activity. After suppression of the primary ATG of the ENG gene, the authors observed high mutant protein levels, almost twice those of the wildtype construct; the authors suggested that there might be competition beween the variant and wildtype AUGs at the translational level. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
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<div>
|
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<p />
|
|
</div>
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<div>
|
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<ol>
|
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|
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<li>
|
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<p class="mim-text-font">
|
|
Abdalla, S. A., Letarte, M.
|
|
<strong>Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease.</strong>
|
|
J. Med. Genet. 43: 97-110, 2006.
|
|
|
|
|
|
[PubMed: 15879500]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2005.030833]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Abdalla, S. A., Pece-Barbara, N., Vera, S., Tapia, E., Paez, E., Bernabeu, C., Letarte, M.
|
|
<strong>Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2.</strong>
|
|
Hum. Molec. Genet. 9: 1227-1237, 2000.
|
|
|
|
|
|
[PubMed: 10767348]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.8.1227]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bayrak-Toydemir, P., McDonald, J., Markewitz, B., Lewin, S., Miller, F., Chou, L.-S., Gedge, F., Tang, W., Coon, H., Mao, R.
|
|
<strong>Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations.</strong>
|
|
Am. J. Med. Genet. 140A: 463-470, 2006.
|
|
|
|
|
|
[PubMed: 16470787]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31101]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bellon, T., Corbi, A., Lastres, P., Cales, C., Cebrian, M., Vera, S., Cheifetz, S., Massague, J., Letarte, M., Bernabeu, C.
|
|
<strong>Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions.</strong>
|
|
Europ. J. Immun. 23: 2340-2345, 1993.
|
|
|
|
|
|
[PubMed: 8370410]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/eji.1830230943]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bourdeau, A., Dumont, D. J., Letarte, M.
|
|
<strong>A murine model of hereditary hemorrhagic telangiectasia.</strong>
|
|
J. Clin. Invest. 104: 1343-1351, 1999.
|
|
|
|
|
|
[PubMed: 10562296]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI8088]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brusgaard, K., Kjeldsen, A. D., Poulsen, L., Moss, H., Vase, P., Rasmussen, K., Kruse, T. A., Horder, M.
|
|
<strong>Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia.</strong>
|
|
Clin. Genet. 66: 556-561, 2004.
|
|
|
|
|
|
[PubMed: 15521985]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2004.00341.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, Y., Hao, Q., Kim, H., Su, H., Letarte, M., Karumanchi, S. A., Lawton, M. T., Barbaro, N. M., Yang, G.-Y., Young, W. L.
|
|
<strong>Soluble endoglin modulates aberrant cerebral vascular remodeling.</strong>
|
|
Ann. Neurol. 66: 19-27, 2009.
|
|
|
|
|
|
[PubMed: 19670444]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.21710]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cymerman, U., Vera, S., Karabegovic, A., Abdalla, S., Letarte, M.
|
|
<strong>Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasia.</strong>
|
|
Hum. Mutat. 21: 482-492, 2003.
|
|
|
|
|
|
[PubMed: 12673790]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10203]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fernandez-Ruiz, E., St. Jacques, S., Bellon, T., Letarte, M., Bernabeu, C.
|
|
<strong>Assignment of the human endoglin gene (END) to 9q34-qter.</strong>
|
|
Cytogenet. Cell Genet. 64: 204-207, 1993.
|
|
|
|
|
|
[PubMed: 8404038]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000133576]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gallione, C. J., Klaus, D. J., Yeh, E. Y., Stenzel, T. T., Xue, Y., Anthony, K. B., McAllister, K. A., Baldwin, M. A., Berg, J. N., Lux, A., Smith, J. D., Vary, C. P. H., Craigen, W. J., Westermann, C. J. J., Warner, M. L., Miller, Y. E., Jackson, C. E., Guttmacher, A. E., Marchuk, D. A.
|
|
<strong>Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.</strong>
|
|
Hum. Mutat. 11: 286-294, 1998.
|
|
|
|
|
|
[PubMed: 9554745]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:4<286::AID-HUMU6>3.0.CO;2-B]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gallione, C. J., Scheessele, E. A., Reinhardt, D., Duits, A. J., Berg, J. N., Westermann, C. J. J., Marchuk, D. A.
|
|
<strong>Two common endoglin mutations in families with hereditary hemorrhagic telangiectasia in the Netherlands Antilles: evidence for a founder effect.</strong>
|
|
Hum. Genet. 107: 40-44, 2000.
|
|
|
|
|
|
[PubMed: 10982033]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390000326]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gougos, A., Letarte, M.
|
|
<strong>Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells.</strong>
|
|
J. Biol. Chem. 265: 8361-8364, 1990.
|
|
|
|
|
|
[PubMed: 1692830]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grisanti, S., Canbek, S., Kaiserling, E., Adam, A., Lafaut, B., Gelisken, F., Szurman, P., Henke-Fahle, S., Oficjalska-Mlynczak, J., Bartz-Schmidt, K. U.
|
|
<strong>Expression of endoglin in choroidal neovascularization.</strong>
|
|
Exp. Eye Res. 78: 207-213, 2004.
|
|
|
|
|
|
[PubMed: 14729353]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.exer.2003.11.008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Howe, J. R., Haidle, J. L., Lal, G., Bair, J., Song, C., Pechman, B., Chinnathambi, S., Lynch, H. T.
|
|
<strong>ENG mutations in MADH4/BMPR1A mutation negative patients with juvenile polyposis. (Letter)</strong>
|
|
Clin. Genet. 71: 91-92, 2007.
|
|
|
|
|
|
[PubMed: 17204053]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00734.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kozak, M.
|
|
<strong>Context effects and inefficient initiation at non-AUG codons in eucaryotic cell-free translation systems.</strong>
|
|
Molec. Cell. Biol. 9: 5073-5080, 1989.
|
|
|
|
|
|
[PubMed: 2601709]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.9.11.5073-5080.1989]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lastella, P., Sabba, C., Lenato, G. M., Resta, N., Lattanzi, W., Gallitelli, M., Cirulli, A., Guanti, G.
|
|
<strong>Endoglin gene mutations and polymorphisms in Italian patients with hereditary haemorrhagic telangiectasia.</strong>
|
|
Clin. Genet. 63: 536-540, 2003.
|
|
|
|
|
|
[PubMed: 12786761]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00081.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lebrin, F., Goumans, M.-J., Jonker, L., Carvalho, R. L. C., Valdimarsdottir, G., Thorikay, M., Mummery, C., Arthur, H. M., ten Dijke, P.
|
|
<strong>Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction.</strong>
|
|
EMBO J. 23: 4018-4028, 2004.
|
|
|
|
|
|
[PubMed: 15385967]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.emboj.7600386]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lebrin, F., Srun, S., Raymond, K., Martin, S., van den Brink, S., Freitas, C., Breant, C., Mathivet, T., Larrivee, B., Thomas, J.-L., Arthur, H. M., Westermann, C. J. J., Disch, F., Mager, J. J., Snijder, R. J., Eichmann, A., Mummery, C. L.
|
|
<strong>Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia.</strong>
|
|
Nature Med. 16: 420-428, 2010.
|
|
|
|
|
|
[PubMed: 20364125]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm.2131]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, N. Y., Ray, B., How, T., Blobe, G. C.
|
|
<strong>Endoglin promotes transforming growth factor beta-mediated Smad 1/5/8 signaling and inhibits endothelial cell migration through its association with GIPC.</strong>
|
|
J. Biol. Chem. 283: 32527-32533, 2008.
|
|
|
|
|
|
[PubMed: 18775991]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M803059200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lesca, G., Plauchu, H., Coulet, F., Lefebvre, S., Plessis, G., Odent, S., Riviere, S., Leheup, B., Goizet, C., Carette, M.-F., Cordier, J.-F., Pinson, S., Soubrier, F., Calender, A., Giraud, S.
|
|
<strong>Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France.</strong>
|
|
Hum. Mutat. 23: 289-299, 2004.
|
|
|
|
|
|
[PubMed: 15024723]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, D. Y., Sorensen, L. K., Brooke, B. S., Urness, L. D., Davis, E. C., Taylor, D. G., Boak, B. B., Wendel, D. P.
|
|
<strong>Defective angiogenesis in mice lacking endoglin.</strong>
|
|
Science 284: 1534-1537, 1999.
|
|
|
|
|
|
[PubMed: 10348742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.284.5419.1534]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lux, A., Gallione, C. J., Marchuk, D. A.
|
|
<strong>Expression analysis of endoglin missense and truncation mutations: insights into protein structure and disease mechanisms.</strong>
|
|
Hum. Molec. Genet. 9: 745-755, 2000.
|
|
|
|
|
|
[PubMed: 10749981]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.5.745]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marchuk, D. A., Srinivasan, S., Squire, T. L., Zawistowski, J. S.
|
|
<strong>Vascular morphogenesis: tales of two syndromes.</strong>
|
|
Hum. Molec. Genet. 12(R1): R97-R112, 2003.
|
|
|
|
|
|
[PubMed: 12668602]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McAllister, K. A., Grogg, K. M., Johnson, D. W., Gallione, C. J., Baldwin, M. A., Jackson, C. E., Helmbold, E. A., Markel, D. S., McKinnon, W. C., Murrell, J., McCormick, M. K., Pericak-Vance, M. A., Heutink, P., Oostra, B. A., Haitjema, T., Westerman, C. J. J., Porteous, M. E., Guttmacher, A. E., Letarte, M., Marchuk, D. A.
|
|
<strong>Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.</strong>
|
|
Nature Genet. 8: 345-351, 1994.
|
|
|
|
|
|
[PubMed: 7894484]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1294-345]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muenzner, P., Bachmann, V., Zimmermann, W., Hentschel, J., Hauck, C. R.
|
|
<strong>Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation.</strong>
|
|
Science 329: 1197-1201, 2010.
|
|
|
|
|
|
[PubMed: 20813953]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1190892]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Paquet, M.-E., Pece-Barbara, N., Vera, S., Cymerman, U., Karabegovic, A., Shovlin, C., Letarte, M.
|
|
<strong>Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function.</strong>
|
|
Hum. Molec. Genet. 10: 1347-1357, 2001.
|
|
|
|
|
|
[PubMed: 11440987]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.13.1347]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pece, N., Vera, S., Cymerman, U., White, R. I., Jr., Wrana, J. L., Letarte, M.
|
|
<strong>Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative.</strong>
|
|
J. Clin. Invest. 100: 2568-2579, 1997.
|
|
|
|
|
|
[PubMed: 9366572]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI119800]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pece-Barbara, N., Cymerman, U., Vera, S., Marchuk, D. A., Letarte, M.
|
|
<strong>Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1.</strong>
|
|
Hum. Molec. Genet. 8: 2171-2181, 1999.
|
|
|
|
|
|
[PubMed: 10545596]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/8.12.2171]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pilz, A., Woodward, K., Peters, J., Povey, S., Abbott, C.
|
|
<strong>Comparative mapping of 38 human chromosome 9 loci in the laboratory mouse. (Abstract)</strong>
|
|
Ann. Hum. Genet. 58: 231-232, 1994.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Qureshi, S. T., Gros, P., Letarte, M., Malo, D.
|
|
<strong>The murine endoglin gene (Eng) maps to chromosome 2.</strong>
|
|
Genomics 26: 165-166, 1995.
|
|
|
|
|
|
[PubMed: 7782079]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(95)80099-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rius, C., Smith, J. D., Almendro, N., Langa, C., Botella, L. M., Marchuk, D. A., Vary, C. P. H., Bernabeu, C.
|
|
<strong>Cloning of the promoter region of human endoglin, the target gene for hereditary hemorrhagic telangiectasia type 1.</strong>
|
|
Blood 92: 4677-4690, 1998.
|
|
|
|
|
|
[PubMed: 9845534]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruiz-Llorente, L., McDonald, J., Wooderchak-Donahue, W., Briggs, E., Chesnutt, M., Bayrak-Toydemir, P., Bernabeu, C.
|
|
<strong>Characterization of a family mutation in the 5-prime untranslated region of the endoglin gene causative of hereditary hemorrhagic telangiectasia.</strong>
|
|
J. Hum. Genet. 64: 333-339, 2019.
|
|
|
|
|
|
[PubMed: 30728427]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s10038-019-0564-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shoukier, M., Teske, U., Weise, A., Engel, W., Argyriou, L.
|
|
<strong>Characterization of five novel large deletions causing hereditary haemorrhagic telangiectasia.</strong>
|
|
Clin. Genet. 73: 320-330, 2008.
|
|
|
|
|
|
[PubMed: 18312453]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2008.00968.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shovlin, C. L., Hughes, J. M. B., Scott, J., Seidman, C. E., Seidman, J. G.
|
|
<strong>Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia.</strong>
|
|
Am. J. Hum. Genet. 61: 68-79, 1997.
|
|
|
|
|
|
[PubMed: 9245986]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/513906]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
Soukarieh, O., Tillet, E., Proust, C., Dupont, C., Jaspard-Vinassa, B., Soubrier, F., Goyenvalle, A., Eyries, M., Tregouet, D. A.
|
|
<strong>uAUG creating variants in the 5-prime-UTR of ENG causing hereditary hemorrhagic telangiectasia.</strong>
|
|
NPJ Genomic Med. 8: 32, 2023.
|
|
|
|
|
|
[PubMed: 37848456]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41525-023-00378-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sweet, K., Willis, J., Zhou, X.-P., Gallione, C., Sawada, T., Alhopuro, P., Khoo, S. K., Patocs, A., Martin, C., Bridgeman, S., Heinz, J., Pilarski, R., Lehtonen, R., Prior, T. W., Frebourg, T., Teh, B. T., Marchuk, D. A., Aaltonen, L. A., Eng, C.
|
|
<strong>Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.</strong>
|
|
JAMA 294: 2465-2473, 2005.
|
|
|
|
|
|
[PubMed: 16287957]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/jama.294.19.2465]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Wang, X., Abraham, S., McKenzie, J. A. G., Jeffs, N., Swire, M., Tripathi, V. B., Luhmann, U. F. O., Lange, C. A. K., Zhai, Z., Arthur, H. M., Bainbridge, J. W. B., Moss, S. E., Greenwood, J.
|
|
<strong>LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling.</strong>
|
|
Nature 499: 306-311, 2013. Note: Erratum: Nature 501: 578 only, 2013.
|
|
|
|
|
|
[PubMed: 23868260]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature12345]
|
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|
|
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</p>
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</li>
|
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|
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<li>
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Wehner, L.-E., Folz, B. J., Argyriou, L., Twelkemeyer, S., Teske, U., Geisthoff, U. W., Werner, J. A., Engel, W., Nayernia, K.
|
|
<strong>Mutation analysis in hereditary haemorrhagic telangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1 mutations.</strong>
|
|
Clin. Genet. 69: 239-245, 2006.
|
|
|
|
|
|
[PubMed: 16542389]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00574.x]
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