3033 lines
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Entry
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- #603776 - HYPERCHOLESTEROLEMIA, FAMILIAL, 3; FHCL3
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- OMIM
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<span class="h4">#603776</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/603776"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS143890"> <strong>Phenotypic Series</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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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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<div><a href="https://clinicaltrials.gov/search?cond=HYPERCHOLESTEROLEMIA, FAMILIAL" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=22639&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK174884/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/8582" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603776[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><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=391665" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div style="display: table-cell;">Animal Models</div>
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</a>
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<div class="panel-body small mim-panel-body">
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<div><a href="https://omia.org/OMIA002329/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<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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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 391665<br />
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">ICD+</a>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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603776
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</span>
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</span>
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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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HYPERCHOLESTEROLEMIA, FAMILIAL, 3; FHCL3
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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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<a id="alternativeTitles" class="mim-anchor"></a>
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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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HYPERCHOLESTEROLEMIA, AUTOSOMAL DOMINANT, 3; HCHOLA3<br />
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FH3
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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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<a id="includedTitles" class="mim-anchor"></a>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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LOW DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 1, INCLUDED; LDLCQ1, INCLUDED
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</span>
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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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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/1/646?start=-3&limit=10&highlight=646">
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1p32.3
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Hypercholesterolemia, familial, 3
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/603776"> 603776 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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PCSK9
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/607786"> 607786 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/1/646?start=-3&limit=10&highlight=646">
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1p32.3
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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{Low density lipoprotein cholesterol level QTL 1}
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/603776"> 603776 </a>
|
|
</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal 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">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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PCSK9
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/607786"> 607786 </a>
|
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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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<a href="/clinicalSynopsis/603776" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
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<span class="sr-only">Toggle Dropdown</span>
|
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</button>
|
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</div>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS143890" class="btn btn-info" role="button"> Phenotypic Series </a>
|
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|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
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<span class="sr-only">Toggle Dropdown</span>
|
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</button>
|
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</div>
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<div class="btn-group">
|
|
<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>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/603776" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/603776" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
|
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<p />
|
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</div>
|
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|
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<div class="small" style="margin: 5px">
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<strong> INHERITANCE </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
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|
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<div>
|
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<span class="mim-font">
|
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|
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- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
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|
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</span>
|
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</div>
|
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|
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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 class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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|
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Arcus corneae <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111522004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111522004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/231924000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">231924000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H18.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H18.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003742&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003742</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001084" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001084</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
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</div>
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|
|
</div>
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</div>
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Heart </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Coronary artery disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414024009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414024009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/443502000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">443502000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/53741008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">53741008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I25.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I25.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K76.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K76.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I25.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I25.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/414.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">414.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1956346&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1956346</a>, <a href="https://bioportal.bioontology.org/search?q=C0010054&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010054</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001677</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
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|
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|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Xanthelasmas <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75594004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75594004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/238951005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">238951005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63103006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63103006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0302314&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0302314</a>, <a href="https://bioportal.bioontology.org/search?q=C0155210&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0155210</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001114" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001114</a>]</span><br /> -
|
|
Tendinous xanthomata <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/69880002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">69880002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221253&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221253</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010874" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010874</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
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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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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- High total cholesterol High LD cholesterol <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5194365&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5194365</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Elevated cholesterol levels evident before age 20<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the proprotein convertase, subtilisin/kexin-type, 9 gene (PCSK9, <a href="/entry/607786#0001">607786.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Hypercholesterolemia, familial
|
|
- <a href="/phenotypicSeries/PS143890">PS143890</a>
|
|
- 10 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/301?start=-3&limit=10&highlight=301"> 1p36.11 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603813"> Hypercholesterolemia, familial, 4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/603813"> 603813 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/605747"> LDLRAP1 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/605747"> 605747 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/1/646?start=-3&limit=10&highlight=646"> 1p32.3 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/603776"> Hypercholesterolemia, familial, 3 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/603776"> 603776 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607786"> PCSK9 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/607786"> 607786 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/1/646?start=-3&limit=10&highlight=646"> 1p32.3 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/603776"> {Low density lipoprotein cholesterol level QTL 1} </a>
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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</span>
|
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</td>
|
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
|
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</td>
|
|
<td>
|
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<span class="mim-font">
|
|
<a href="/entry/603776"> 603776 </a>
|
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</span>
|
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</td>
|
|
<td>
|
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<span class="mim-font">
|
|
<a href="/entry/607786"> PCSK9 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/607786"> 607786 </a>
|
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</span>
|
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</td>
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</tr>
|
|
|
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<tr>
|
|
<td>
|
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<span class="mim-font">
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<a href="/geneMap/1/1346?start=-3&limit=10&highlight=1346"> 1q23.3 </a>
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> {Hypercholesterolemia, familial, modifier of} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> 143890 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107670"> APOA2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107670"> 107670 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/80?start=-3&limit=10&highlight=80"> 2p24.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/144010"> Hypercholesterolemia, familial, 2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/144010"> 144010 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107730"> APOB </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107730"> 107730 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/5/139?start=-3&limit=10&highlight=139"> 5p13.1-p12 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> {Hypercholesterolemia, familial, modifier of} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> 143890 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600946"> GHR </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600946"> 600946 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/173?start=-3&limit=10&highlight=173"> 7p14.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> {Hypercholesterolemia, susceptibility to} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> 143890 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604088"> GSBS </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604088"> 604088 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/152?start=-3&limit=10&highlight=152"> 8p21.2-p21.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> {Hypercholesterolemia, familial, due to LDLR defect, modifier of} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> 143890 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/132811"> EPHX2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/132811"> 132811 </a>
|
|
</span>
|
|
</td>
|
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</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/288?start=-3&limit=10&highlight=288"> 19p13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> Hypercholesterolemia, familial, 1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> 143890 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606945"> LDLR </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606945"> 606945 </a>
|
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</span>
|
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</td>
|
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</tr>
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|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/288?start=-3&limit=10&highlight=288"> 19p13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> LDL cholesterol level QTL2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/143890"> 143890 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606945"> LDLR </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606945"> 606945 </a>
|
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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 class="text-right small">
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
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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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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that autosomal dominant familial hypercholesterolemia-3 (FHCL3) is caused by heterozygous gain-of-function mutation in the PCSK9 gene (<a href="/entry/607786">607786</a>) on chromosome 1p32.</p><p>Low density lipoprotein cholesterol level quantitative trait locus-1 (LDLCQ1) is associated with heterozygous loss-of-function mutation in the PCSK9 gene.</p>
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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="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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<div id="mimDescriptionFold" class="collapse in ">
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<p>Familial hypercholesterolemia-3 (FHCL3) is an autosomal dominant disorder of lipid metabolism characterized by a selective increase of low density lipoprotein particles in plasma, giving rise to tendon and skin xanthomas, arcus corneae, and coronary artery disease (summary by <a href="#6" class="mim-tip-reference" title="Varret, M., Rabes, J.-P., Saint-Jore, B., Cenarro, A., Marinoni, J.-C., Civeira, F., Devillers, M., Krempf, M., Coulon, M., Thiart, R., Kotze, M. J., Schmidt, H., and 9 others. <strong>A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.</strong> Am. J. Hum. Genet. 64: 1378-1387, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10205269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10205269</a>] [<a href="https://doi.org/10.1086/302370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10205269">Varret et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10205269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For a general description and a discussion of genetic heterogeneity of hypercholesterolemia, see <a href="/entry/143890">143890</a>.</p><p><a href="#6" class="mim-tip-reference" title="Varret, M., Rabes, J.-P., Saint-Jore, B., Cenarro, A., Marinoni, J.-C., Civeira, F., Devillers, M., Krempf, M., Coulon, M., Thiart, R., Kotze, M. J., Schmidt, H., and 9 others. <strong>A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.</strong> Am. J. Hum. Genet. 64: 1378-1387, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10205269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10205269</a>] [<a href="https://doi.org/10.1086/302370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10205269">Varret et al. (1999)</a> reported a large 3-generation French family (HC2) in which 7 individuals had hypercholesterolemia. All affected members had levels of total cholesterol above the 97th percentile when compared with age- and sex-matched French individuals. The proband was a 36-year-old woman, ascertained at age 17 years with 3.32 g/l total cholesterol, 2.36 g/l LDL-C, 0.48 g/l HDL-C, 0.61 g/l triglycerides, and arcus corneae. Her sister, aged 40 years, was ascertained at age 20 years with similar lipid levels, arcus corneae, tendon xanthomas, and xanthelasmas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10205269" 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="Haddad, L., Day, I. N. M., Hunt, S., Williams, R. R., Humphries, S. E., Hopkins, P. N. <strong>Evidence for a third genetic locus causing familial hypercholesterolemia: a non-LDLR, non-APOB kindred.</strong> J. Lipid Res. 40: 1113-1122, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10357843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10357843</a>]" pmid="10357843">Haddad et al. (1999)</a> reported a large Utah kindred (K1173) segregating hypercholesterolemia. In this pedigree, the LDL levels (mean, 237 +/-70) were similar to those of familial hypercholesterolemia pedigrees with mutations in the LDL receptor gene (FHCL1; <a href="/entry/606945">606945</a>), and penetrance was complete even at young ages. Triglyceride levels were significantly lower than in FHCL1 pedigrees, but mean age and body mass index were also lower. There were no differences in the frequency of tendon xanthomas or coronary artery disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10357843" 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>The transmission pattern of hyercholesterolemia in the French family reported by <a href="#6" class="mim-tip-reference" title="Varret, M., Rabes, J.-P., Saint-Jore, B., Cenarro, A., Marinoni, J.-C., Civeira, F., Devillers, M., Krempf, M., Coulon, M., Thiart, R., Kotze, M. J., Schmidt, H., and 9 others. <strong>A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.</strong> Am. J. Hum. Genet. 64: 1378-1387, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10205269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10205269</a>] [<a href="https://doi.org/10.1086/302370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10205269">Varret et al. (1999)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10205269" 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="#6" class="mim-tip-reference" title="Varret, M., Rabes, J.-P., Saint-Jore, B., Cenarro, A., Marinoni, J.-C., Civeira, F., Devillers, M., Krempf, M., Coulon, M., Thiart, R., Kotze, M. J., Schmidt, H., and 9 others. <strong>A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.</strong> Am. J. Hum. Genet. 64: 1378-1387, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10205269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10205269</a>] [<a href="https://doi.org/10.1086/302370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10205269">Varret et al. (1999)</a> identified a large French pedigree and 12 additional Caucasian families with autosomal dominant hypercholesterolemia in which linkage to both the LDLR gene (<a href="/entry/606945">606945</a>) and the APOB gene (<a href="/entry/107730">107730</a>) was excluded, implicating a new locus, which they designated FH3. A lod score of 3.13 at a recombination fraction of 0.0 was obtained at markers D1S2892 and D1S2722. <a href="#6" class="mim-tip-reference" title="Varret, M., Rabes, J.-P., Saint-Jore, B., Cenarro, A., Marinoni, J.-C., Civeira, F., Devillers, M., Krempf, M., Coulon, M., Thiart, R., Kotze, M. J., Schmidt, H., and 9 others. <strong>A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.</strong> Am. J. Hum. Genet. 64: 1378-1387, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10205269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10205269</a>] [<a href="https://doi.org/10.1086/302370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10205269">Varret et al. (1999)</a> localized the FH3 locus to a 9-cM interval at 1p34.1-p32. Heterogeneity tests indicated linkage to FH3 in approximately 27% of these non-LDLR/non-APOB autosomal dominant hypercholesterolemia families, implying the existence of yet a fourth locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10205269" 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="#4" class="mim-tip-reference" title="Hunt, S. C., Hopkins, P. N., Bulka, K., McDermott, M. T., Thorne, T. L., Wardell, B. B., Bowen, B. R., Ballinger, D. G., Skolnick, M. H., Samuels, M. E. <strong>Genetic localization to chromosome 1p32 of the third locus for familial hypercholesterolemia in a Utah kindred.</strong> Arterioscler. Thromb. Vasc. Biol. 20: 1089-1093, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10764678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10764678</a>] [<a href="https://doi.org/10.1161/01.atv.20.4.1089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10764678">Hunt et al. (2000)</a> found that familial hypercholesterolemia in a Utah kindred (K1173), previously described by <a href="#3" class="mim-tip-reference" title="Haddad, L., Day, I. N. M., Hunt, S., Williams, R. R., Humphries, S. E., Hopkins, P. N. <strong>Evidence for a third genetic locus causing familial hypercholesterolemia: a non-LDLR, non-APOB kindred.</strong> J. Lipid Res. 40: 1113-1122, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10357843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10357843</a>]" pmid="10357843">Haddad et al. (1999)</a>, mapped to 1p32. <a href="#4" class="mim-tip-reference" title="Hunt, S. C., Hopkins, P. N., Bulka, K., McDermott, M. T., Thorne, T. L., Wardell, B. B., Bowen, B. R., Ballinger, D. G., Skolnick, M. H., Samuels, M. E. <strong>Genetic localization to chromosome 1p32 of the third locus for familial hypercholesterolemia in a Utah kindred.</strong> Arterioscler. Thromb. Vasc. Biol. 20: 1089-1093, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10764678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10764678</a>] [<a href="https://doi.org/10.1161/01.atv.20.4.1089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10764678">Hunt et al. (2000)</a> mapped the disorder to a region of approximately 17 cM between markers D1S2130 and D1S1596. This region appeared to overlap the region found to be linked to severe hypercholesterolemia in French and Spanish families by <a href="#6" class="mim-tip-reference" title="Varret, M., Rabes, J.-P., Saint-Jore, B., Cenarro, A., Marinoni, J.-C., Civeira, F., Devillers, M., Krempf, M., Coulon, M., Thiart, R., Kotze, M. J., Schmidt, H., and 9 others. <strong>A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.</strong> Am. J. Hum. Genet. 64: 1378-1387, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10205269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10205269</a>] [<a href="https://doi.org/10.1086/302370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10205269">Varret et al. (1999)</a>. By expansion of the K1173 pedigree and increased marker density within the region of interest, <a href="#5" class="mim-tip-reference" title="Timms, K. M., Wagner, S., Samuels, M. E., Forbey, K., Goldfine, H., Jammulapati, S., Skolnick, M. H., Hopkins, P. N., Hunt, S. C., Shattuck, D. M. <strong>A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree.</strong> Hum. Genet. 114: 349-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14727179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14727179</a>] [<a href="https://doi.org/10.1007/s00439-003-1071-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14727179">Timms et al. (2004)</a> narrowed the linked region. They also identified additional families sharing the same microsatellite haplotype. Whereas all haplotype carriers in the K1173 kindred were affected, the haplotype carriers within the newly identified families were unaffected, suggesting that the causal mutation had occurred after divergence of these pedigrees from a common ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10357843+10205269+10764678+14727179" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Abifadel, M., Varret, M., Rabes, J.-P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., Derre, A., Villeger, L., and 14 others. <strong>Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.</strong> Nature Genet. 34: 154-156, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12730697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12730697</a>] [<a href="https://doi.org/10.1038/ng1161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12730697">Abifadel et al. (2003)</a> carried out positional cloning using the French family (HC92) in which linkage was originally identified by <a href="#6" class="mim-tip-reference" title="Varret, M., Rabes, J.-P., Saint-Jore, B., Cenarro, A., Marinoni, J.-C., Civeira, F., Devillers, M., Krempf, M., Coulon, M., Thiart, R., Kotze, M. J., Schmidt, H., and 9 others. <strong>A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.</strong> Am. J. Hum. Genet. 64: 1378-1387, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10205269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10205269</a>] [<a href="https://doi.org/10.1086/302370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10205269">Varret et al. (1999)</a> and 23 French families in which involvement of LDLR (<a href="/entry/606945">606945</a>) and APOB (<a href="/entry/107730">107730</a>) had been excluded as the site of causative mutations. The critical region was found to contain 41 genes, including PCSK9 (<a href="/entry/607786">607786</a>). They identified PCSK9 mutations (<a href="/entry/607786#0001">607786.0001</a> and <a href="/entry/607786#0002">607786.0002</a>) in 3 French families with hypercholesterolemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12730697+10205269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By mutation screening of genes in the chromosome 1p32 region in patients with familial hypercholesterolemia from the Utah pedigree (K1173) studied by <a href="#3" class="mim-tip-reference" title="Haddad, L., Day, I. N. M., Hunt, S., Williams, R. R., Humphries, S. E., Hopkins, P. N. <strong>Evidence for a third genetic locus causing familial hypercholesterolemia: a non-LDLR, non-APOB kindred.</strong> J. Lipid Res. 40: 1113-1122, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10357843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10357843</a>]" pmid="10357843">Haddad et al. (1999)</a> and <a href="#4" class="mim-tip-reference" title="Hunt, S. C., Hopkins, P. N., Bulka, K., McDermott, M. T., Thorne, T. L., Wardell, B. B., Bowen, B. R., Ballinger, D. G., Skolnick, M. H., Samuels, M. E. <strong>Genetic localization to chromosome 1p32 of the third locus for familial hypercholesterolemia in a Utah kindred.</strong> Arterioscler. Thromb. Vasc. Biol. 20: 1089-1093, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10764678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10764678</a>] [<a href="https://doi.org/10.1161/01.atv.20.4.1089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10764678">Hunt et al. (2000)</a>, <a href="#5" class="mim-tip-reference" title="Timms, K. M., Wagner, S., Samuels, M. E., Forbey, K., Goldfine, H., Jammulapati, S., Skolnick, M. H., Hopkins, P. N., Hunt, S. C., Shattuck, D. M. <strong>A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree.</strong> Hum. Genet. 114: 349-353, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14727179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14727179</a>] [<a href="https://doi.org/10.1007/s00439-003-1071-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14727179">Timms et al. (2004)</a> identified a D374Y (<a href="/entry/607786#0003">607786.0003</a>) mutation in the PCSK9 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10357843+10764678+14727179" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 of 64 African American subjects with low plasma levels of low density lipoprotein cholesterol (LDLCQ1), <a href="#2" class="mim-tip-reference" title="Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., Hobbs, H. H. <strong>Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9.</strong> Nature Genet. 37: 161-165, 2005. Note: Erratum: Nature Genet. 37: 328 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15654334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15654334</a>] [<a href="https://doi.org/10.1038/ng1509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15654334">Cohen et al. (2005)</a> identified a nonsense mutation (Y142X; <a href="/entry/607786#0004">607786.0004</a>) in the PCSK9 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15654334" 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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Abifadel, M., Varret, M., Rabes, J.-P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., Derre, A., Villeger, L., and 14 others.
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<strong>Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.</strong>
|
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Nature Genet. 34: 154-156, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12730697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12730697</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12730697" 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/ng1161" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="2" class="mim-anchor"></a>
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<a id="Cohen2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., Hobbs, H. H.
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<strong>Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9.</strong>
|
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Nature Genet. 37: 161-165, 2005. Note: Erratum: Nature Genet. 37: 328 only, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15654334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15654334</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15654334" 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/ng1509" target="_blank">Full Text</a>]
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<li>
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<a id="3" class="mim-anchor"></a>
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<a id="Haddad1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Haddad, L., Day, I. N. M., Hunt, S., Williams, R. R., Humphries, S. E., Hopkins, P. N.
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<strong>Evidence for a third genetic locus causing familial hypercholesterolemia: a non-LDLR, non-APOB kindred.</strong>
|
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J. Lipid Res. 40: 1113-1122, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10357843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10357843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10357843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="4" class="mim-anchor"></a>
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<a id="Hunt2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hunt, S. C., Hopkins, P. N., Bulka, K., McDermott, M. T., Thorne, T. L., Wardell, B. B., Bowen, B. R., Ballinger, D. G., Skolnick, M. H., Samuels, M. E.
|
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<strong>Genetic localization to chromosome 1p32 of the third locus for familial hypercholesterolemia in a Utah kindred.</strong>
|
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Arterioscler. Thromb. Vasc. Biol. 20: 1089-1093, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10764678/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10764678</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10764678" 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/10.1161/01.atv.20.4.1089" target="_blank">Full Text</a>]
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Timms2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Timms, K. M., Wagner, S., Samuels, M. E., Forbey, K., Goldfine, H., Jammulapati, S., Skolnick, M. H., Hopkins, P. N., Hunt, S. C., Shattuck, D. M.
|
|
<strong>A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree.</strong>
|
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Hum. Genet. 114: 349-353, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14727179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14727179</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14727179" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-003-1071-9" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Varret1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Varret, M., Rabes, J.-P., Saint-Jore, B., Cenarro, A., Marinoni, J.-C., Civeira, F., Devillers, M., Krempf, M., Coulon, M., Thiart, R., Kotze, M. J., Schmidt, H., and 9 others.
|
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<strong>A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.</strong>
|
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Am. J. Hum. Genet. 64: 1378-1387, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10205269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10205269</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10205269" 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/10.1086/302370" target="_blank">Full Text</a>]
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</ol>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick - updated : 5/13/2003
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick - updated : 12/27/2002
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</span>
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</div>
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</div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 4/26/1999
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/20/2019
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</span>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/19/2019<br>carol : 06/19/2019<br>carol : 02/15/2012<br>wwang : 5/21/2008<br>alopez : 6/3/2003<br>alopez : 5/29/2003<br>alopez : 5/29/2003<br>alopez : 5/16/2003<br>alopez : 5/14/2003<br>terry : 5/13/2003<br>cwells : 12/30/2002<br>terry : 12/27/2002<br>alopez : 9/11/2002<br>mgross : 9/23/1999<br>terry : 5/20/1999<br>mgross : 5/3/1999
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</span>
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</div>
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</div>
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>#</strong> 603776
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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HYPERCHOLESTEROLEMIA, FAMILIAL, 3; FHCL3
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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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<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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<h4>
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<span class="mim-font">
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HYPERCHOLESTEROLEMIA, AUTOSOMAL DOMINANT, 3; HCHOLA3<br />
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FH3
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</span>
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</h4>
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</div>
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<div>
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<br />
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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LOW DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 1, INCLUDED; LDLCQ1, INCLUDED
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</span>
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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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<p>
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<span class="mim-text-font">
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<strong>ORPHA:</strong> 391665;
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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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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
|
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Gene/Locus <br /> MIM number
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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>
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<td>
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<span class="mim-font">
|
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1p32.3
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Hypercholesterolemia, familial, 3
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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603776
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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PCSK9
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</span>
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</td>
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<td>
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<span class="mim-font">
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607786
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<tr>
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<td>
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<span class="mim-font">
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1p32.3
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</td>
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<td>
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<span class="mim-font">
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{Low density lipoprotein cholesterol level QTL 1}
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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603776
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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PCSK9
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</span>
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</td>
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<td>
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<span class="mim-font">
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607786
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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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<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>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
|
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<p>A number sign (#) is used with this entry because of evidence that autosomal dominant familial hypercholesterolemia-3 (FHCL3) is caused by heterozygous gain-of-function mutation in the PCSK9 gene (607786) on chromosome 1p32.</p><p>Low density lipoprotein cholesterol level quantitative trait locus-1 (LDLCQ1) is associated with heterozygous loss-of-function mutation in the PCSK9 gene.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Familial hypercholesterolemia-3 (FHCL3) is an autosomal dominant disorder of lipid metabolism characterized by a selective increase of low density lipoprotein particles in plasma, giving rise to tendon and skin xanthomas, arcus corneae, and coronary artery disease (summary by Varret et al., 1999). </p><p>For a general description and a discussion of genetic heterogeneity of hypercholesterolemia, see 143890.</p><p>Varret et al. (1999) reported a large 3-generation French family (HC2) in which 7 individuals had hypercholesterolemia. All affected members had levels of total cholesterol above the 97th percentile when compared with age- and sex-matched French individuals. The proband was a 36-year-old woman, ascertained at age 17 years with 3.32 g/l total cholesterol, 2.36 g/l LDL-C, 0.48 g/l HDL-C, 0.61 g/l triglycerides, and arcus corneae. Her sister, aged 40 years, was ascertained at age 20 years with similar lipid levels, arcus corneae, tendon xanthomas, and xanthelasmas. </p><p>Haddad et al. (1999) reported a large Utah kindred (K1173) segregating hypercholesterolemia. In this pedigree, the LDL levels (mean, 237 +/-70) were similar to those of familial hypercholesterolemia pedigrees with mutations in the LDL receptor gene (FHCL1; 606945), and penetrance was complete even at young ages. Triglyceride levels were significantly lower than in FHCL1 pedigrees, but mean age and body mass index were also lower. There were no differences in the frequency of tendon xanthomas or coronary artery disease. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Inheritance</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>The transmission pattern of hyercholesterolemia in the French family reported by Varret et al. (1999) was consistent with autosomal dominant inheritance. </p>
|
|
</span>
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<div>
|
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<br />
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</div>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Varret et al. (1999) identified a large French pedigree and 12 additional Caucasian families with autosomal dominant hypercholesterolemia in which linkage to both the LDLR gene (606945) and the APOB gene (107730) was excluded, implicating a new locus, which they designated FH3. A lod score of 3.13 at a recombination fraction of 0.0 was obtained at markers D1S2892 and D1S2722. Varret et al. (1999) localized the FH3 locus to a 9-cM interval at 1p34.1-p32. Heterogeneity tests indicated linkage to FH3 in approximately 27% of these non-LDLR/non-APOB autosomal dominant hypercholesterolemia families, implying the existence of yet a fourth locus. </p><p>Hunt et al. (2000) found that familial hypercholesterolemia in a Utah kindred (K1173), previously described by Haddad et al. (1999), mapped to 1p32. Hunt et al. (2000) mapped the disorder to a region of approximately 17 cM between markers D1S2130 and D1S1596. This region appeared to overlap the region found to be linked to severe hypercholesterolemia in French and Spanish families by Varret et al. (1999). By expansion of the K1173 pedigree and increased marker density within the region of interest, Timms et al. (2004) narrowed the linked region. They also identified additional families sharing the same microsatellite haplotype. Whereas all haplotype carriers in the K1173 kindred were affected, the haplotype carriers within the newly identified families were unaffected, suggesting that the causal mutation had occurred after divergence of these pedigrees from a common ancestor. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>Abifadel et al. (2003) carried out positional cloning using the French family (HC92) in which linkage was originally identified by Varret et al. (1999) and 23 French families in which involvement of LDLR (606945) and APOB (107730) had been excluded as the site of causative mutations. The critical region was found to contain 41 genes, including PCSK9 (607786). They identified PCSK9 mutations (607786.0001 and 607786.0002) in 3 French families with hypercholesterolemia. </p><p>By mutation screening of genes in the chromosome 1p32 region in patients with familial hypercholesterolemia from the Utah pedigree (K1173) studied by Haddad et al. (1999) and Hunt et al. (2000), Timms et al. (2004) identified a D374Y (607786.0003) mutation in the PCSK9 gene. </p><p>In 3 of 64 African American subjects with low plasma levels of low density lipoprotein cholesterol (LDLCQ1), Cohen et al. (2005) identified a nonsense mutation (Y142X; 607786.0004) in the PCSK9 gene. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p />
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</div>
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<ol>
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<li>
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Abifadel, M., Varret, M., Rabes, J.-P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., Derre, A., Villeger, L., and 14 others.
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<strong>Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.</strong>
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Nature Genet. 34: 154-156, 2003.
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[PubMed: 12730697]
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[Full Text: https://doi.org/10.1038/ng1161]
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<p class="mim-text-font">
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Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., Hobbs, H. H.
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<strong>Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9.</strong>
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Nature Genet. 37: 161-165, 2005. Note: Erratum: Nature Genet. 37: 328 only, 2005.
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[PubMed: 15654334]
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[Full Text: https://doi.org/10.1038/ng1509]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Haddad, L., Day, I. N. M., Hunt, S., Williams, R. R., Humphries, S. E., Hopkins, P. N.
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<strong>Evidence for a third genetic locus causing familial hypercholesterolemia: a non-LDLR, non-APOB kindred.</strong>
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J. Lipid Res. 40: 1113-1122, 1999.
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[PubMed: 10357843]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hunt, S. C., Hopkins, P. N., Bulka, K., McDermott, M. T., Thorne, T. L., Wardell, B. B., Bowen, B. R., Ballinger, D. G., Skolnick, M. H., Samuels, M. E.
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<strong>Genetic localization to chromosome 1p32 of the third locus for familial hypercholesterolemia in a Utah kindred.</strong>
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Arterioscler. Thromb. Vasc. Biol. 20: 1089-1093, 2000.
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[PubMed: 10764678]
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[Full Text: https://doi.org/10.1161/01.atv.20.4.1089]
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<li>
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<p class="mim-text-font">
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Timms, K. M., Wagner, S., Samuels, M. E., Forbey, K., Goldfine, H., Jammulapati, S., Skolnick, M. H., Hopkins, P. N., Hunt, S. C., Shattuck, D. M.
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<strong>A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree.</strong>
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Hum. Genet. 114: 349-353, 2004.
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[PubMed: 14727179]
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[Full Text: https://doi.org/10.1007/s00439-003-1071-9]
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</p>
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<li>
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<p class="mim-text-font">
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Varret, M., Rabes, J.-P., Saint-Jore, B., Cenarro, A., Marinoni, J.-C., Civeira, F., Devillers, M., Krempf, M., Coulon, M., Thiart, R., Kotze, M. J., Schmidt, H., and 9 others.
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<strong>A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.</strong>
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Am. J. Hum. Genet. 64: 1378-1387, 1999.
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[PubMed: 10205269]
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[Full Text: https://doi.org/10.1086/302370]
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</p>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick - updated : 5/13/2003<br>Victor A. McKusick - updated : 12/27/2002
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<span class="mim-text-font">
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Victor A. McKusick : 4/26/1999
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carol : 06/20/2019<br>carol : 06/19/2019<br>carol : 06/19/2019<br>carol : 02/15/2012<br>wwang : 5/21/2008<br>alopez : 6/3/2003<br>alopez : 5/29/2003<br>alopez : 5/29/2003<br>alopez : 5/16/2003<br>alopez : 5/14/2003<br>terry : 5/13/2003<br>cwells : 12/30/2002<br>terry : 12/27/2002<br>alopez : 9/11/2002<br>mgross : 9/23/1999<br>terry : 5/20/1999<br>mgross : 5/3/1999
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