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<title>
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Entry
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- #613688 - LONG QT SYNDROME 2; LQT2
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- OMIM
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<span class="h4">#613688</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/phenotypicSeries/PS192500"> <strong>Phenotypic Series</strong> </a>
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<a href="#description">Description</a>
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<a href="#mapping">Mapping</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</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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<a href="#editHistory"><strong>Edit History</strong></a>
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<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
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<div><a href="https://www.diseaseinfosearch.org/x/4300" 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://medlineplus.gov/genetics/condition/romano-ward-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=613688[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 style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Romano-Ward syndrome</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=768" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Familial long QT syndrome</a></div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0110645" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/613688" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://omia.org/OMIA002333/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0110645" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 101016, 768<br />
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<strong>DO:</strong> 0110645<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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613688
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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LONG QT SYNDROME 2; LQT2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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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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LONG QT SYNDROME 1/2, DIGENIC, INCLUDED; LQT1/2, DIGENIC, INCLUDED
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</span>
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</div>
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<div>
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<span class="h4 mim-font">
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LONG QT SYNDROME 2/3, DIGENIC, INCLUDED; LQT2/3, DIGENIC, INCLUDED<br />
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LONG QT SYNDROME 2/5, DIGENIC, INCLUDED; LQT2/5, DIGENIC, INCLUDED<br />
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LONG QT SYNDROME 2/9, DIGENIC, INCLUDED; LQT2/9, DIGENIC, 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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<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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</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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<a href="/geneMap/7/821?start=-3&limit=10&highlight=821">
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7q36.1
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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">
|
|
Long QT syndrome 2
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
<a href="/entry/613688"> 613688 </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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</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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KCNH2
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/152427"> 152427 </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>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/12/285?start=-3&limit=10&highlight=285">
|
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12q12
|
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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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{Long QT syndrome, acquired, reduced susceptibility to}
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613688"> 613688 </a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
ALG10B
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603313"> 603313 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
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|
|
</tbody>
|
|
</table>
|
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</div>
|
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</div>
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<div>
|
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|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/613688" 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>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
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</div>
|
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|
|
<div class="btn-group">
|
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|
|
<a href="/phenotypicSeries/PS192500" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<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>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</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>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/613688" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/613688" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</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>
|
|
<p />
|
|
</div>
|
|
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|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- 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 />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</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">
|
|
|
|
- Prolonged QT interval on EKG <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111975006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111975006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151878&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151878</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001657" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001657</a>]</span><br /> -
|
|
Syncope <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/272030005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">272030005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271594007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271594007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/309585006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">309585006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R55" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R55</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3541349&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3541349</a>, <a href="https://bioportal.bioontology.org/search?q=C0039070&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039070</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001279" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001279</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0007185" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007185</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001279" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001279</a>]</span><br /> -
|
|
Sudden cardiac death <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95281009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95281009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085298&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085298</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001645" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001645</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001645" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001645</a>]</span><br /> -
|
|
Ventricular fibrillation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/164896001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">164896001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71908006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71908006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I49.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I49.01</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/427.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042510&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042510</a>, <a href="https://bioportal.bioontology.org/search?q=C0344435&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344435</a>, <a href="https://bioportal.bioontology.org/search?q=C2108112&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2108112</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001663</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001663</a>]</span><br /> -
|
|
Torsade de pointes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/31722008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">31722008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I47.21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I47.21</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040479&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040479</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001664" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001664</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001664" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001664</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
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- Association of cardiac events with exercise<br /> -
|
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Genetic heterogeneity (see LQT1 <a href="/entry/192500">192500</a>) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0242960&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0242960</a>]</span><br /> -
|
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Patients with a more severe phenotype have been reported with mutations in more than 1 LQTS-related gene<br /> -
|
|
GEI (gene-environment interaction) - association of cardiac events with drug administration<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the potassium voltage-gated channel, subfamily H, member 2 gene or human ether-a-go-go related gene (KCNH2, <a href="/entry/152427#0001">152427.0001</a>)<br />
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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 class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
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</div>
|
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</div>
|
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</div>
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|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<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>
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Long QT syndrome
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- <a href="/phenotypicSeries/PS192500">PS192500</a>
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|
- 21 Entries
|
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</h5>
|
|
</div>
|
|
</div>
|
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|
|
<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/2/236?start=-3&limit=10&highlight=236"> 2p21 </a>
|
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|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616249"> Long QT syndrome 15 </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/616249"> 616249 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/114182"> CALM2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/114182"> 114182 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/27?start=-3&limit=10&highlight=27"> 3p25.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611818"> Long QT syndrome 9 </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/611818"> 611818 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601253"> CAV3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601253"> 601253 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/181?start=-3&limit=10&highlight=181"> 3p22.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603830"> Long QT syndrome 3 </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/603830"> 603830 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600163"> SCN5A </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600163"> 600163 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/502?start=-3&limit=10&highlight=502"> 4q25-q26 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600919"> Long QT syndrome 4 </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/600919"> 600919 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/106410"> ANK2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/106410"> 106410 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/502?start=-3&limit=10&highlight=502"> 4q25-q26 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600919"> Cardiac arrhythmia, ankyrin-B-related </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/600919"> 600919 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/106410"> ANK2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/106410"> 106410 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/404?start=-3&limit=10&highlight=404"> 7q21.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611820"> ?Long QT syndrome 11 </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/611820"> 611820 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604001"> AKAP9 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604001"> 604001 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/821?start=-3&limit=10&highlight=821"> 7q36.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613688"> Long QT syndrome 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/613688"> 613688 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/152427"> KCNH2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/152427"> 152427 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/82?start=-3&limit=10&highlight=82"> 11p15.5-p15.4 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/192500"> {Long QT syndrome 1, acquired, susceptibility to} </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/192500"> 192500 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607542"> KCNQ1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607542"> 607542 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/82?start=-3&limit=10&highlight=82"> 11p15.5-p15.4 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/192500"> Long QT syndrome 1 </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/192500"> 192500 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607542"> KCNQ1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607542"> 607542 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/976?start=-3&limit=10&highlight=976"> 11q23.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611819"> Atrial fibrillation, familial, 17 </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/611819"> 611819 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608256"> SCN4B </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608256"> 608256 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/976?start=-3&limit=10&highlight=976"> 11q23.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
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<span class="mim-font">
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<a href="/entry/611819"> Long QT syndrome 10 </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/611819"> 611819 </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/608256"> SCN4B </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/608256"> 608256 </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/11/1085?start=-3&limit=10&highlight=1085"> 11q24.3 </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/613485"> Long QT syndrome 13 </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/613485"> 613485 </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/600734"> KCNJ5 </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/600734"> 600734 </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/12/18?start=-3&limit=10&highlight=18"> 12p13.33 </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/618447"> Long QT syndrome 8 </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/618447"> 618447 </a>
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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<a href="/entry/114205"> CACNA1C </a>
|
|
</span>
|
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</td>
|
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<td>
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|
<span class="mim-font">
|
|
<a href="/entry/114205"> 114205 </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/12/285?start=-3&limit=10&highlight=285"> 12q12 </a>
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|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613688"> {Long QT syndrome, acquired, reduced susceptibility to} </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/613688"> 613688 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603313"> ALG10B </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603313"> 603313 </a>
|
|
</span>
|
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</td>
|
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</tr>
|
|
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|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/455?start=-3&limit=10&highlight=455"> 14q32.11 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616247"> Long QT syndrome 14 </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/616247"> 616247 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/114180"> CALM1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/114180"> 114180 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/893?start=-3&limit=10&highlight=893"> 17q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/170390"> Andersen syndrome </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/170390"> 170390 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600681"> KCNJ2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600681"> 600681 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/854?start=-3&limit=10&highlight=854"> 19q13.32 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618782"> ?Ventricular tachycardia, catecholaminergic polymorphic 6 </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/618782"> 618782 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/114183"> CALM3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/114183"> 114183 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/854?start=-3&limit=10&highlight=854"> 19q13.32 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618782"> Long QT syndrome 16 </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/618782"> 618782 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/114183"> CALM3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/114183"> 114183 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/20/213?start=-3&limit=10&highlight=213"> 20q11.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612955"> Long QT syndrome 12 </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/612955"> 612955 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601017"> SNTA1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601017"> 601017 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/21/79?start=-3&limit=10&highlight=79"> 21q22.11 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613693"> Long QT syndrome 6 </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/613693"> 613693 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603796"> KCNE2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603796"> 603796 </a>
|
|
</span>
|
|
</td>
|
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</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/21/80?start=-3&limit=10&highlight=80"> 21q22.12 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613695"> Long QT syndrome 5 </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/613695"> 613695 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/176261"> KCNE1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/176261"> 176261 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</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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</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="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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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because long QT syndrome-2 (LQT2) is caused by heterozygous mutation in the HERG gene (KCNH2; <a href="/entry/152427">152427</a>) on chromosome 7q36.</p><p>Digenic inheritance has also been reported; see MOLECULAR GENETICS.</p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<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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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (<a href="#7" class="mim-tip-reference" title="Jongbloed, R. J. E., Wilde, A. A. M., Geelen, J. L. M. C., Doevendans, P., Schaap, C., Van Langen, I., van Tintelen, J. P., Cobben, J. M., Beaufort-Krol, G. C. M., Geraedts, J. P. M., Smeets, H. J. M. <strong>Novel KCNQ1 and HERG missense mutations in Dutch long-QT families.</strong> Hum. Mutat. 13: 301-310, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10220144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10220144</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)13:4<301::AID-HUMU7>3.0.CO;2-V" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10220144">Jongbloed et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10220144" 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 discussion of genetic heterogeneity of long QT syndrome, see LQT1 (<a href="/entry/192500">192500</a>).</p>
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<p><a href="#6" class="mim-tip-reference" title="Jiang, C., Atkinson, D., Towbin, J. A., Splawski, I., Lehmann, M. H., Li, H., Timothy, K., Taggart, R. T., Schwartz, P. J., Vincent, G. M., Moss, A. J., Keating, M. T. <strong>Two long QT syndrome loci map to chromosomes 3 and 7 with evidence for further heterogeneity.</strong> Nature Genet. 8: 141-147, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7842012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7842012</a>] [<a href="https://doi.org/10.1038/ng1094-141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7842012">Jiang et al. (1994)</a> found linkage to D7S483 at chromosome 7q35-q36 in 9 families with the long QT syndrome; the combined lod score was 19.41 at theta = 0.001. <a href="#3" class="mim-tip-reference" title="Curran, M. E., Splawski, I., Timothy, K. W., Vincent, G. M., Green, E. D., Keating, M. T. <strong>A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.</strong> Cell 80: 795-803, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7889573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7889573</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90358-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7889573">Curran et al. (1995)</a> showed that the KCNH2 gene mapped to the same YAC as D7S505, a polymorphic marker tightly linked to LQT2. They found no recombination events using linkage analysis with polymorphisms within KCNH2 for linkage studies of chromosome 7-linked LQT. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7842012+7889573" 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="#3" class="mim-tip-reference" title="Curran, M. E., Splawski, I., Timothy, K. W., Vincent, G. M., Green, E. D., Keating, M. T. <strong>A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.</strong> Cell 80: 795-803, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7889573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7889573</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90358-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7889573">Curran et al. (1995)</a> noted that 2 hypotheses for LQT had previously been proposed. One suggested that a predominance of left autonomic innervation caused abnormal cardiac repolarization and arrhythmias. This hypothesis was supported by the finding that arrhythmias can be induced in dogs by removal of the right stellate ganglion. In addition, anecdotal evidence suggested that some LQT patients are effectively treated by beta-adrenergic blocking agents and by left stellate ganglionectomy. The second hypothesis for LQT-related arrhythmias suggested that mutations in cardiac-specific ion channel genes (or genes that modulate cardiac ion channels) cause delayed myocellular repolarization. Delayed myocellular repolarization could promote reactivation of L-type Ca(2+) channels, resulting in secondary depolarizations. These secondary depolarizations are the likely cellular mechanism of torsade de pointes arrhythmias. This hypothesis is supported by the observation that pharmacologic block of potassium channels can induce QT prolongation and repolarization-related arrhythmias in human and animal models. The discovery that one form of LQT results from mutations in a cardiac potassium channel gene supported the myocellular hypothesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7889573" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a surrogate model of LQT2, <a href="#1" class="mim-tip-reference" title="Akar, F. G., Yan, G.-X., Antzelevitch, C., Rosenbaum, D. S. <strong>Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome.</strong> Circulation 105: 1247-1253, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11889021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11889021</a>] [<a href="https://doi.org/10.1161/hc1002.105231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11889021">Akar et al. (2002)</a> investigated a mechanism by which dysfunction at the molecular level may provide the electrical substrate for the life-threatening arrhythmia torsade de pointes. The authors used the novel approach of transmural optical imaging in a canine wedge preparation to determine the spatial organization of repolarization and arrhythmogenesis. They demonstrated islands of midmyocardial cells (M cells) with increased refractoriness, producing steep spatial gradients of repolarization that were directly responsible for conduction block and self-sustained intramural reentrant circuits. These data highlighted a central role for M cells in the development of reentrant torsade de pointes in LQT2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11889021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Roden, D. M., Viswanathan, P. C. <strong>Genetics of acquired long QT syndrome.</strong> J. Clin. Invest. 115: 2025-2032, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16075043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16075043</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16075043[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI25539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16075043">Roden and Viswanathan (2005)</a> reviewed the genetics of acquired long QT syndrome and discussed the structural features of the HERG channel that render it more vulnerable to blockade by drugs: the presence of multiple aromatic residues oriented to face the permeation pore, which provide high-affinity binding sites for a wide range of compounds; and the absence of a pair of proline residues in the S6 helix that forms part of the pore, resulting in an unkinked S6 helix in the HERG channel that is hypothesized to increase access to the binding site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16075043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Itzhaki, I., Maizels, L., Huber, I., Zwi-Dantsis, L., Caspi, O., Winterstern, A., Feldman, O., Gepstein, A., Arbel, G., Hammerman, H., Boulos, M., Gepstein, L. <strong>Modelling the long QT syndrome with induced pluripotent stem cells.</strong> Nature 471: 225-229, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21240260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21240260</a>] [<a href="https://doi.org/10.1038/nature09747" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21240260">Itzhaki et al. (2011)</a> reported the development of a patient/disease-specific human induced pluripotent stem cell (iPSC) line from a patient with long QT syndrome-2 that was due to an A614V missense mutation in the KCNH2 gene (<a href="/entry/152427#0026">152427.0026</a>). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes when compared to healthy control cells. Voltage-clamp studies confirmed that this action potential duration prolongation stems from a significant reduction of the cardiac potassium current I(Kr). Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. <a href="#5" class="mim-tip-reference" title="Itzhaki, I., Maizels, L., Huber, I., Zwi-Dantsis, L., Caspi, O., Winterstern, A., Feldman, O., Gepstein, A., Arbel, G., Hammerman, H., Boulos, M., Gepstein, L. <strong>Modelling the long QT syndrome with induced pluripotent stem cells.</strong> Nature 471: 225-229, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21240260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21240260</a>] [<a href="https://doi.org/10.1038/nature09747" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21240260">Itzhaki et al. (2011)</a> then used the LQTS human iPSC-derived cardiac tissue model to evaluate the potency of existing and novel pharmacologic agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K(ATP)-channel openers, and late sodium-channel blockers) the disease phenotype. <a href="#5" class="mim-tip-reference" title="Itzhaki, I., Maizels, L., Huber, I., Zwi-Dantsis, L., Caspi, O., Winterstern, A., Feldman, O., Gepstein, A., Arbel, G., Hammerman, H., Boulos, M., Gepstein, L. <strong>Modelling the long QT syndrome with induced pluripotent stem cells.</strong> Nature 471: 225-229, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21240260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21240260</a>] [<a href="https://doi.org/10.1038/nature09747" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21240260">Itzhaki et al. (2011)</a> concluded that their study illustrated the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21240260" 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>Although inheritance of the long QT syndrome is autosomal dominant, female predominance has often been observed and has sometimes been attributed to an increased susceptibility to cardiac arrhythmias in women. <a href="#4" class="mim-tip-reference" title="Imboden, M., Swan, H., Denjoy, I., Van Langen, I. M., Latinen-Forsblom, P. J., Napolitano, C., Fressart, V., Breithardt, G., Berthet, M., Priori, S., Hainque, B., Wilde, A. A. M., Schulze-Bahr, E., Feingold, J., Guicheney, P. <strong>Female predominance and transmission distortion in the long-QT syndrome.</strong> New Eng. J. Med. 355: 2744-2751, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17192539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17192539</a>] [<a href="https://doi.org/10.1056/NEJMoa042786" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17192539">Imboden et al. (2006)</a> demonstrated distortion in the transmission of the mutant alleles in both LQT1 and LQT2. They investigated the distribution of mutant alleles in 484 nuclear families with LQT1 (<a href="/entry/192500">192500</a>) and 169 nuclear families with LQT2, all with fully genotyped offspring. Classic mendelian inheritance ratios were not observed in the offspring of either female carriers of LQT1 or male and female carriers of LQT2. Among the 1,534 descendants, the proportion of genetically affected offspring was significantly greater than that expected according to mendelian inheritance: 870 were carriers of a mutation (57%), and 664 were noncarriers (43%) (p less than 0.001). Among the 870 carriers, the allele for the long QT syndrome was transmitted more often to female offspring (55%) than to male offspring (45%) (p = 0.005). Increased maternal transmission of the long QT syndrome mutation to daughters was also observed, possibly contributing to the excess of female patients with autosomal dominant long QT syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17192539" 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>Defective protein trafficking is a possible consequence of gene mutation. Trafficking-defective mutant HERG proteins are characterized by a reduced delayed rectifier potassium current and give rise to LQT2. High-affinity HERG channel-blocking drugs can result in pharmacologic rescue of this current. <a href="#14" class="mim-tip-reference" title="Rajamani, S., Anderson, C. L., Anson, B. D., January, C. T. <strong>Pharmacological rescue of human K+ channel long-QT2 mutations.</strong> Circulation 105: 2830-2835, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12070109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12070109</a>] [<a href="https://doi.org/10.1161/01.cir.0000019513.50928.74" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12070109">Rajamani et al. (2002)</a> studied the electrophysiologic consequences of pharmacologic mutant HERG blockade using 2 blocking agents. One compound, fexofenadine, rescued the electrophysiologic defect without complete channel blockade, suggesting that this might be a useful treatment for some LQT2 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12070109" 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="#3" class="mim-tip-reference" title="Curran, M. E., Splawski, I., Timothy, K. W., Vincent, G. M., Green, E. D., Keating, M. T. <strong>A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.</strong> Cell 80: 795-803, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7889573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7889573</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90358-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7889573">Curran et al. (1995)</a> performed single-strand conformation polymorphism and DNA sequence analyses and detected HERG mutations in 6 LQT families, including 2 intragenic deletions, 1 splice-donor mutation, and 3 missense mutations. In 1 kindred, the mutation arose de novo. Northern blot analyses showed that HERG is highly expressed in the heart. The data were interpreted as indicating that mutation in the HERG gene is responsible for LQT2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7889573" 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="#19" class="mim-tip-reference" title="Zhou, Z., Gong, Q., Epstein, M. L., January, C. T. <strong>HERG channel dysfunction in human long QT syndrome: intracellular transport and functional defects.</strong> J. Biol. Chem. 273: 21061-21066, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9694858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9694858</a>] [<a href="https://doi.org/10.1074/jbc.273.33.21061" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9694858">Zhou et al. (1998)</a> used electrophysiologic, biochemical, and immunohistochemical methods to study the molecular mechanisms of HERG channel dysfunction caused by LQT2 mutations. They found that some mutations, e.g., tyr611 to his and val822 to met (<a href="/entry/152427#0005">152427.0005</a>), caused defects in biosynthetic processing of HERG channels with the protein retained in the endoplasmic reticulum (ER). Other mutations, e.g., ile593 to arg (<a href="/entry/152427#0004">152427.0004</a>) and gly628 to ser (<a href="/entry/152427#0008">152427.0008</a>), were processed similarly to wildtype HERG protein, but these mutations did not produce functional channels. In contrast, the thr474-to-ile mutation expressed HERG current but with altered gating properties. These findings suggested that the loss of HERG channel function in LQT2 mutations is caused by multiple mechanisms including abnormal channel processing, the generation of nonfunctional channels, and altered channel gating. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9694858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Priori, S. G., Napolitano, C., Schwartz, P. J. <strong>Low penetrance in the long QT syndrome: clinical impact.</strong> Circulation 99: 529-533, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9927399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9927399</a>] [<a href="https://doi.org/10.1161/01.cir.99.4.529" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9927399">Priori et al. (1999)</a> identified 9 families, each with a 'sporadic' case of LQTS, i.e., only the proband was diagnosed clinically as being affected by LQTS. Six probands were symptomatic for syncope, 2 were asymptomatic with QT prolongation found on routine examination, and 1 was asymptomatic but showed QT prolongation when examined following her brother's sudden death while swimming. Five had mutations in HERG (4 missense, 1 nonsense) and 4 had missense mutations in KCNQ1 (<a href="/entry/607542">607542</a>). Four of the mutations were de novo; in the remaining families at least 1 silent gene carrier was found, allowing estimation of penetrance at 25%. This contrasted greatly with the prevailing view that LQTS gene mutations may have penetrances of 90% or more. This study highlighted the importance of detecting such silent gene carriers since they are at risk of developing torsade de pointes if exposed to drugs that block potassium channels. Further, the authors stated, carrier status cannot be reliably excluded on clinical grounds alone. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9927399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Dutch family with long QT syndrome in which affected members carried an A558P mutation in the KCNH2 gene in heterozygosity (<a href="/entry/152427#0025">152427.0025</a>), <a href="#2" class="mim-tip-reference" title="Amin, A. S., Herfst, L. J., Delisle, B. P., Klemens, C. A., Rook, M. B., Bezzina, C. R., Underkofler, H. A. S., Holzem, K. M., Ruijter, J. M., Tan, H. L., January, C. T., Wilde, A. A. M. <strong>Fever-induced QTc prolongation and ventricular arrhythmias in individuals with type 2 congenital long QT syndrome.</strong> J. Clin. Invest. 118: 2552-2561, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18551196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18551196</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18551196[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI35337" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18551196">Amin et al. (2008)</a> described fever-induced QT prolongation and demonstrated that the A558P mutation is trafficking-deficient, that it has a dominant-negative effect in coassembly with wildtype subunits, and that its current density fails to increase with increasing temperature to the same extent as wildtype channels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18551196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Digenic Inheritance</em></strong></p><p>
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<a href="#17" class="mim-tip-reference" title="Tester, D. J., Will, M. L., Haglund, C. M., Ackerman, M. J. <strong>Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.</strong> Heart Rhythm 2: 507-517, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15840476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15840476</a>] [<a href="https://doi.org/10.1016/j.hrthm.2005.01.020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15840476">Tester et al. (2005)</a> analyzed 5 LQTS-associated cardiac channel genes in 541 consecutive unrelated patients with LQT syndrome (average QTc, 482 ms). In 272 (50%) patients, they identified 211 different pathogenic mutations, including 88 in KCNQ1, 89 in KCNH2, 32 in SCN5A, and 1 each in KCNE1 and KCNE2. Mutations considered pathogenic were absent in more than 1,400 reference alleles. Among the mutation-positive patients, 29 (11%) had 2 LQTS-causing mutations, of which 16 (8%) were in 2 different LQTS genes (biallelic digenic). <a href="#17" class="mim-tip-reference" title="Tester, D. J., Will, M. L., Haglund, C. M., Ackerman, M. J. <strong>Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.</strong> Heart Rhythm 2: 507-517, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15840476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15840476</a>] [<a href="https://doi.org/10.1016/j.hrthm.2005.01.020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15840476">Tester et al. (2005)</a> noted that patients with multiple mutations were younger at diagnosis, but they did not discern any genotype/phenotype correlations associated with location or type of mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15840476" 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 44 unrelated patients with LQT syndrome, <a href="#9" class="mim-tip-reference" title="Millat, G., Chevalier, P., Restier-Miron, L., Da Costa, A., Bouvagnet, P., Kugener, B., Fayol, L., Gonzalez Armengod, C., Oddou, B., Chanavat, V., Froidefond, E., Perraudin, R., Rousson, R., Rodriguez-Lafrasse, C. <strong>Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.</strong> Clin. Genet. 70: 214-227, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16922724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16922724</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00671.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16922724">Millat et al. (2006)</a> used DHLP chromatography to analyze the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes for mutations and SNPs. Most of the patients (84%) showed a complex molecular pattern, with an identified mutation associated with 1 or more SNPs located in several LQTS genes; 4 of the patients also had a second mutation in a different LQTS gene (biallelic digenic inheritance; see, e.g., <a href="/entry/152427#0020">152427.0020</a> and <a href="/entry/152427#0022">152427.0022</a>-<a href="/entry/152427#0023">152427.0023</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16922724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Reviews</em></strong></p><p>
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A comprehensive review of the genetic and molecular bases of long QT syndromes was provided by Priori et al. (<a href="#11" class="mim-tip-reference" title="Priori, S. G., Barhanin, J., Hauer, R. N. W., Haverkamp, W., Jongsma, H. J., Kleber, A. G., McKenna, W. J., Roden, D. M., Rudy, Y., Schwartz, K., Schwartz, P. J., Towbin, J. A., Wilde, A. M. <strong>Genetic and molecular basis of cardiac arrhythmias: impact on clinical management. Part III.</strong> Circulation 99: 674-681, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9950666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9950666</a>] [<a href="https://doi.org/10.1161/01.cir.99.5.674" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9950666">1999</a>, <a href="#12" class="mim-tip-reference" title="Priori, S. G., Barhanin, J., Hauer, R. N. W., Haverkamp, W., Jongsma, H. J., Kleber, A. G., McKenna, W. J., Roden, D. M., Rudy, Y., Schwartz, K., Schwartz, P. J., Towbin, J. A., Wilde, A. M. <strong>Genetic and molecular basis of cardiac arrhythmias: impact on clinical management. Parts I and II.</strong> Circulation 99: 518-528, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9927398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9927398</a>] [<a href="https://doi.org/10.1161/01.cir.99.4.518" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9927398">1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9927398+9950666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a large collaborative study, <a href="#18" class="mim-tip-reference" title="Zareba, W., Moss, A. J., Schwartz, P. J., Vincent, G. M., Robinson, J. L., Priori, S. G., Benhorin, J., Locati, E. H., Towbin, J. A., Keating, M. T., Lehmann, M. H., Hall, W. J., International Long-QT Syndrome Registry Research Group. <strong>Influence of the genotype on the clinical course of the long-QT syndrome.</strong> New Eng. J. Med. 339: 960-965, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9753711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9753711</a>] [<a href="https://doi.org/10.1056/NEJM199810013391404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9753711">Zareba et al. (1998)</a> determined the influence of genotype on phenotype of the long QT syndrome; 112 persons had mutations at the LQT1 locus, 72 had mutations at the LQT2 locus, and 62 had mutations at the LQT3 (<a href="/entry/603830">603830</a>) locus. The frequency of cardiac events (syncope, aborted cardiac arrest, or sudden death) was highest with mutations at the LQT1 locus (63%) or the LQT2 locus (46%) than among subjects with mutations at the LQT3 locus (18%). The cumulative mortality through the age of 40 among members of 3 groups of families studied was similar; however, the likelihood of dying during a cardiac event was significantly higher among families with mutations at the LQT3 locus (20%) than among those with mutations at the LQT1 locus (4%) or the LQT2 locus (4%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9753711" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Moss, A. J., Zareba, W., Kaufman, E. S., Gartman, E., Peterson, D. R., Benhorin, J., Towbin, J. A., Keating, M. T., Priori, S. G., Schwartz, P. J., Vincent, G. M., Robinson, J. L., Andrews, M. L., Feng, C., Hall, W. J., Medina, A., Zhang, L., Wang, Z. <strong>Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel.</strong> Circulation 105: 794-799, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11854117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11854117</a>] [<a href="https://doi.org/10.1161/hc0702.105124" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11854117">Moss et al. (2002)</a> investigated the clinical features and prognostic implications of mutations involving the pore and nonpore regions of the HERG channel in LQT2. Forty-four different mutations in this gene were identified in 201 subjects, with 14 localized to the pore region (amino acid residues 550 through 650). A total of 35 individuals had mutations in the pore region and 166 in nonpore regions. Those with pore mutations had a markedly increased risk for arrhythmia-associated cardiac events (syncope, cardiac arrest, or sudden death) compared with those with nonpore mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11854117" 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>Through homologous recombination in mouse embryonic stem cells, <a href="#8" class="mim-tip-reference" title="Lees-Miller, J. P., Guo, J., Somers, J. R., Roach, D. E., Sheldon, R. S., Rancourt, D. E., Duff, H. J. <strong>Selective knockout of mouse ERG1 B potassium channel eliminates I(Kr) in adult ventricular myocytes and elicits episodes of abrupt sinus bradycardia.</strong> Molec. Cell. Biol. 23: 1856-1862, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12612061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12612061</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12612061[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.23.6.1856-1862.2003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12612061">Lees-Miller et al. (2003)</a> eliminated the ERG1 B potassium channel transcript while the ERG1 A transcript remained. Heterologous expression of ERG1 isoforms had previously indicated that the deactivation time course of ERG1 B is 10-fold more rapid than that of ERG1 A. In day 18 fetal +/+ myocytes, I(Kr) exhibited 2 time constants of deactivation, whereas in age-matched ERG1 B -/- mice the rapid component was absent. In adult ERG1 B -/- myocytes no I(Kr) was detected. Electrocardiogram intervals were similar in 6 of 21 +/+ and -/- mice; however, adult -/- mice manifested abrupt spontaneous episodes of sinus bradycardia. This phenomenon was never observed in +/+ mice. Thus, ERG1 B appears to be necessary for I(Kr) expression in the surface membrane of adult myocytes. <a href="#8" class="mim-tip-reference" title="Lees-Miller, J. P., Guo, J., Somers, J. R., Roach, D. E., Sheldon, R. S., Rancourt, D. E., Duff, H. J. <strong>Selective knockout of mouse ERG1 B potassium channel eliminates I(Kr) in adult ventricular myocytes and elicits episodes of abrupt sinus bradycardia.</strong> Molec. Cell. Biol. 23: 1856-1862, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12612061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12612061</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12612061[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.23.6.1856-1862.2003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12612061">Lees-Miller et al. (2003)</a> concluded that knockout of ERG1 B predisposes mice to episodic sinus bradycardia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12612061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a porcine model of postmyocardial infarction ventricular tachycardia, <a href="#16" class="mim-tip-reference" title="Sasano, T., McDonald, A. D., Kikuchi, K., Donahue, J. K. <strong>Molecular ablation of ventricular tachycardia after myocardial infarction.</strong> Nature Med. 12: 1256-1268, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17072309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17072309</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17072309[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm1503" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17072309">Sasano et al. (2006)</a> demonstrated that focal gene transfer of the dominant-negative mutant G628S (<a href="/entry/152427#0008">152427.0008</a>) to the infarct scar border zone resulted in complete elimination of ventricular arrhythmia inducibility, showing that gene transfer can eliminate cardiac tachyarrhythmias in a clinically relevant disease model. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17072309" 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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Circulation 105: 1247-1253, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11889021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11889021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11889021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Amin, A. S., Herfst, L. J., Delisle, B. P., Klemens, C. A., Rook, M. B., Bezzina, C. R., Underkofler, H. A. S., Holzem, K. M., Ruijter, J. M., Tan, H. L., January, C. T., Wilde, A. A. M.
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<strong>Fever-induced QTc prolongation and ventricular arrhythmias in individuals with type 2 congenital long QT syndrome.</strong>
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J. Clin. Invest. 118: 2552-2561, 2008.
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[<a href="https://doi.org/10.1161/01.cir.99.5.674" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/01.cir.99.4.518" target="_blank">Full Text</a>]
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Zareba, W., Moss, A. J., Schwartz, P. J., Vincent, G. M., Robinson, J. L., Priori, S. G., Benhorin, J., Locati, E. H., Towbin, J. A., Keating, M. T., Lehmann, M. H., Hall, W. J., International Long-QT Syndrome Registry Research Group.
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<strong>Influence of the genotype on the clinical course of the long-QT syndrome.</strong>
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New Eng. J. Med. 339: 960-965, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9753711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9753711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9753711" 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/10.1056/NEJM199810013391404" target="_blank">Full Text</a>]
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<a id="19" class="mim-anchor"></a>
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<a id="Zhou1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhou, Z., Gong, Q., Epstein, M. L., January, C. T.
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<strong>HERG channel dysfunction in human long QT syndrome: intracellular transport and functional defects.</strong>
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J. Biol. Chem. 273: 21061-21066, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9694858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9694858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9694858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.273.33.21061" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 6/14/2011
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Creation Date:
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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 A. Bocchini : 1/13/2011
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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alopez : 09/30/2024
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carol : 10/19/2022<br>carol : 10/19/2022<br>alopez : 06/22/2022<br>mgross : 03/11/2019<br>carol : 04/23/2017<br>joanna : 06/29/2016<br>carol : 9/18/2015<br>alopez : 6/12/2014<br>alopez : 2/2/2012<br>alopez : 2/2/2012<br>carol : 11/28/2011<br>alopez : 6/17/2011<br>terry : 6/14/2011<br>terry : 1/14/2011<br>carol : 1/13/2011<br>carol : 1/13/2011
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<span class="mim-font">
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<strong>#</strong> 613688
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LONG QT SYNDROME 2; LQT2
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Other entities represented in this entry:
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<span class="h3 mim-font">
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LONG QT SYNDROME 1/2, DIGENIC, INCLUDED; LQT1/2, DIGENIC, INCLUDED
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<span class="h4 mim-font">
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LONG QT SYNDROME 2/3, DIGENIC, INCLUDED; LQT2/3, DIGENIC, INCLUDED<br />
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LONG QT SYNDROME 2/5, DIGENIC, INCLUDED; LQT2/5, DIGENIC, INCLUDED<br />
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LONG QT SYNDROME 2/9, DIGENIC, INCLUDED; LQT2/9, DIGENIC, INCLUDED
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<strong>ORPHA:</strong> 101016, 768;
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<strong>DO:</strong> 0110645;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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7q36.1
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<span class="mim-font">
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Long QT syndrome 2
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<span class="mim-font">
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613688
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<span class="mim-font">
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KCNH2
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<span class="mim-font">
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152427
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12q12
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<span class="mim-font">
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{Long QT syndrome, acquired, reduced susceptibility to}
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<span class="mim-font">
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613688
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<span class="mim-font">
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ALG10B
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<span class="mim-font">
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603313
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<strong>TEXT</strong>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because long QT syndrome-2 (LQT2) is caused by heterozygous mutation in the HERG gene (KCNH2; 152427) on chromosome 7q36.</p><p>Digenic inheritance has also been reported; see MOLECULAR GENETICS.</p>
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<span class="mim-font">
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (Jongbloed et al., 1999). </p><p>For a discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500).</p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Jiang et al. (1994) found linkage to D7S483 at chromosome 7q35-q36 in 9 families with the long QT syndrome; the combined lod score was 19.41 at theta = 0.001. Curran et al. (1995) showed that the KCNH2 gene mapped to the same YAC as D7S505, a polymorphic marker tightly linked to LQT2. They found no recombination events using linkage analysis with polymorphisms within KCNH2 for linkage studies of chromosome 7-linked LQT. </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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<strong>Pathogenesis</strong>
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<span class="mim-text-font">
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<p>Curran et al. (1995) noted that 2 hypotheses for LQT had previously been proposed. One suggested that a predominance of left autonomic innervation caused abnormal cardiac repolarization and arrhythmias. This hypothesis was supported by the finding that arrhythmias can be induced in dogs by removal of the right stellate ganglion. In addition, anecdotal evidence suggested that some LQT patients are effectively treated by beta-adrenergic blocking agents and by left stellate ganglionectomy. The second hypothesis for LQT-related arrhythmias suggested that mutations in cardiac-specific ion channel genes (or genes that modulate cardiac ion channels) cause delayed myocellular repolarization. Delayed myocellular repolarization could promote reactivation of L-type Ca(2+) channels, resulting in secondary depolarizations. These secondary depolarizations are the likely cellular mechanism of torsade de pointes arrhythmias. This hypothesis is supported by the observation that pharmacologic block of potassium channels can induce QT prolongation and repolarization-related arrhythmias in human and animal models. The discovery that one form of LQT results from mutations in a cardiac potassium channel gene supported the myocellular hypothesis. </p><p>In a surrogate model of LQT2, Akar et al. (2002) investigated a mechanism by which dysfunction at the molecular level may provide the electrical substrate for the life-threatening arrhythmia torsade de pointes. The authors used the novel approach of transmural optical imaging in a canine wedge preparation to determine the spatial organization of repolarization and arrhythmogenesis. They demonstrated islands of midmyocardial cells (M cells) with increased refractoriness, producing steep spatial gradients of repolarization that were directly responsible for conduction block and self-sustained intramural reentrant circuits. These data highlighted a central role for M cells in the development of reentrant torsade de pointes in LQT2. </p><p>Roden and Viswanathan (2005) reviewed the genetics of acquired long QT syndrome and discussed the structural features of the HERG channel that render it more vulnerable to blockade by drugs: the presence of multiple aromatic residues oriented to face the permeation pore, which provide high-affinity binding sites for a wide range of compounds; and the absence of a pair of proline residues in the S6 helix that forms part of the pore, resulting in an unkinked S6 helix in the HERG channel that is hypothesized to increase access to the binding site. </p><p>Itzhaki et al. (2011) reported the development of a patient/disease-specific human induced pluripotent stem cell (iPSC) line from a patient with long QT syndrome-2 that was due to an A614V missense mutation in the KCNH2 gene (152427.0026). The generated iPSCs were coaxed to differentiate into the cardiac lineage. Detailed whole-cell patch-clamp and extracellular multielectrode recordings revealed significant prolongation of the action-potential duration in LQTS human iPSC-derived cardiomyocytes when compared to healthy control cells. Voltage-clamp studies confirmed that this action potential duration prolongation stems from a significant reduction of the cardiac potassium current I(Kr). Importantly, LQTS-derived cells also showed marked arrhythmogenicity, characterized by early-after depolarizations and triggered arrhythmias. Itzhaki et al. (2011) then used the LQTS human iPSC-derived cardiac tissue model to evaluate the potency of existing and novel pharmacologic agents that may either aggravate (potassium-channel blockers) or ameliorate (calcium-channel blockers, K(ATP)-channel openers, and late sodium-channel blockers) the disease phenotype. Itzhaki et al. (2011) concluded that their study illustrated the ability of human iPSC technology to model the abnormal functional phenotype of an inherited cardiac disorder and to identify potential new therapeutic agents. </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>Although inheritance of the long QT syndrome is autosomal dominant, female predominance has often been observed and has sometimes been attributed to an increased susceptibility to cardiac arrhythmias in women. Imboden et al. (2006) demonstrated distortion in the transmission of the mutant alleles in both LQT1 and LQT2. They investigated the distribution of mutant alleles in 484 nuclear families with LQT1 (192500) and 169 nuclear families with LQT2, all with fully genotyped offspring. Classic mendelian inheritance ratios were not observed in the offspring of either female carriers of LQT1 or male and female carriers of LQT2. Among the 1,534 descendants, the proportion of genetically affected offspring was significantly greater than that expected according to mendelian inheritance: 870 were carriers of a mutation (57%), and 664 were noncarriers (43%) (p less than 0.001). Among the 870 carriers, the allele for the long QT syndrome was transmitted more often to female offspring (55%) than to male offspring (45%) (p = 0.005). Increased maternal transmission of the long QT syndrome mutation to daughters was also observed, possibly contributing to the excess of female patients with autosomal dominant long QT syndrome. </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>Clinical Management</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>Defective protein trafficking is a possible consequence of gene mutation. Trafficking-defective mutant HERG proteins are characterized by a reduced delayed rectifier potassium current and give rise to LQT2. High-affinity HERG channel-blocking drugs can result in pharmacologic rescue of this current. Rajamani et al. (2002) studied the electrophysiologic consequences of pharmacologic mutant HERG blockade using 2 blocking agents. One compound, fexofenadine, rescued the electrophysiologic defect without complete channel blockade, suggesting that this might be a useful treatment for some LQT2 patients. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Curran et al. (1995) performed single-strand conformation polymorphism and DNA sequence analyses and detected HERG mutations in 6 LQT families, including 2 intragenic deletions, 1 splice-donor mutation, and 3 missense mutations. In 1 kindred, the mutation arose de novo. Northern blot analyses showed that HERG is highly expressed in the heart. The data were interpreted as indicating that mutation in the HERG gene is responsible for LQT2. </p><p>Zhou et al. (1998) used electrophysiologic, biochemical, and immunohistochemical methods to study the molecular mechanisms of HERG channel dysfunction caused by LQT2 mutations. They found that some mutations, e.g., tyr611 to his and val822 to met (152427.0005), caused defects in biosynthetic processing of HERG channels with the protein retained in the endoplasmic reticulum (ER). Other mutations, e.g., ile593 to arg (152427.0004) and gly628 to ser (152427.0008), were processed similarly to wildtype HERG protein, but these mutations did not produce functional channels. In contrast, the thr474-to-ile mutation expressed HERG current but with altered gating properties. These findings suggested that the loss of HERG channel function in LQT2 mutations is caused by multiple mechanisms including abnormal channel processing, the generation of nonfunctional channels, and altered channel gating. </p><p>Priori et al. (1999) identified 9 families, each with a 'sporadic' case of LQTS, i.e., only the proband was diagnosed clinically as being affected by LQTS. Six probands were symptomatic for syncope, 2 were asymptomatic with QT prolongation found on routine examination, and 1 was asymptomatic but showed QT prolongation when examined following her brother's sudden death while swimming. Five had mutations in HERG (4 missense, 1 nonsense) and 4 had missense mutations in KCNQ1 (607542). Four of the mutations were de novo; in the remaining families at least 1 silent gene carrier was found, allowing estimation of penetrance at 25%. This contrasted greatly with the prevailing view that LQTS gene mutations may have penetrances of 90% or more. This study highlighted the importance of detecting such silent gene carriers since they are at risk of developing torsade de pointes if exposed to drugs that block potassium channels. Further, the authors stated, carrier status cannot be reliably excluded on clinical grounds alone. </p><p>In a Dutch family with long QT syndrome in which affected members carried an A558P mutation in the KCNH2 gene in heterozygosity (152427.0025), Amin et al. (2008) described fever-induced QT prolongation and demonstrated that the A558P mutation is trafficking-deficient, that it has a dominant-negative effect in coassembly with wildtype subunits, and that its current density fails to increase with increasing temperature to the same extent as wildtype channels. </p><p><strong><em>Digenic Inheritance</em></strong></p><p>
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Tester et al. (2005) analyzed 5 LQTS-associated cardiac channel genes in 541 consecutive unrelated patients with LQT syndrome (average QTc, 482 ms). In 272 (50%) patients, they identified 211 different pathogenic mutations, including 88 in KCNQ1, 89 in KCNH2, 32 in SCN5A, and 1 each in KCNE1 and KCNE2. Mutations considered pathogenic were absent in more than 1,400 reference alleles. Among the mutation-positive patients, 29 (11%) had 2 LQTS-causing mutations, of which 16 (8%) were in 2 different LQTS genes (biallelic digenic). Tester et al. (2005) noted that patients with multiple mutations were younger at diagnosis, but they did not discern any genotype/phenotype correlations associated with location or type of mutation. </p><p>In 44 unrelated patients with LQT syndrome, Millat et al. (2006) used DHLP chromatography to analyze the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes for mutations and SNPs. Most of the patients (84%) showed a complex molecular pattern, with an identified mutation associated with 1 or more SNPs located in several LQTS genes; 4 of the patients also had a second mutation in a different LQTS gene (biallelic digenic inheritance; see, e.g., 152427.0020 and 152427.0022-152427.0023). </p><p><strong><em>Reviews</em></strong></p><p>
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A comprehensive review of the genetic and molecular bases of long QT syndromes was provided by Priori et al. (1999, 1999). </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</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>In a large collaborative study, Zareba et al. (1998) determined the influence of genotype on phenotype of the long QT syndrome; 112 persons had mutations at the LQT1 locus, 72 had mutations at the LQT2 locus, and 62 had mutations at the LQT3 (603830) locus. The frequency of cardiac events (syncope, aborted cardiac arrest, or sudden death) was highest with mutations at the LQT1 locus (63%) or the LQT2 locus (46%) than among subjects with mutations at the LQT3 locus (18%). The cumulative mortality through the age of 40 among members of 3 groups of families studied was similar; however, the likelihood of dying during a cardiac event was significantly higher among families with mutations at the LQT3 locus (20%) than among those with mutations at the LQT1 locus (4%) or the LQT2 locus (4%). </p><p>Moss et al. (2002) investigated the clinical features and prognostic implications of mutations involving the pore and nonpore regions of the HERG channel in LQT2. Forty-four different mutations in this gene were identified in 201 subjects, with 14 localized to the pore region (amino acid residues 550 through 650). A total of 35 individuals had mutations in the pore region and 166 in nonpore regions. Those with pore mutations had a markedly increased risk for arrhythmia-associated cardiac events (syncope, cardiac arrest, or sudden death) compared with those with nonpore mutations. </p>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Through homologous recombination in mouse embryonic stem cells, Lees-Miller et al. (2003) eliminated the ERG1 B potassium channel transcript while the ERG1 A transcript remained. Heterologous expression of ERG1 isoforms had previously indicated that the deactivation time course of ERG1 B is 10-fold more rapid than that of ERG1 A. In day 18 fetal +/+ myocytes, I(Kr) exhibited 2 time constants of deactivation, whereas in age-matched ERG1 B -/- mice the rapid component was absent. In adult ERG1 B -/- myocytes no I(Kr) was detected. Electrocardiogram intervals were similar in 6 of 21 +/+ and -/- mice; however, adult -/- mice manifested abrupt spontaneous episodes of sinus bradycardia. This phenomenon was never observed in +/+ mice. Thus, ERG1 B appears to be necessary for I(Kr) expression in the surface membrane of adult myocytes. Lees-Miller et al. (2003) concluded that knockout of ERG1 B predisposes mice to episodic sinus bradycardia. </p><p>In a porcine model of postmyocardial infarction ventricular tachycardia, Sasano et al. (2006) demonstrated that focal gene transfer of the dominant-negative mutant G628S (152427.0008) to the infarct scar border zone resulted in complete elimination of ventricular arrhythmia inducibility, showing that gene transfer can eliminate cardiac tachyarrhythmias in a clinically relevant disease model. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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Jongbloed, R. J. E., Wilde, A. A. M., Geelen, J. L. M. C., Doevendans, P., Schaap, C., Van Langen, I., van Tintelen, J. P., Cobben, J. M., Beaufort-Krol, G. C. M., Geraedts, J. P. M., Smeets, H. J. M.
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Lees-Miller, J. P., Guo, J., Somers, J. R., Roach, D. E., Sheldon, R. S., Rancourt, D. E., Duff, H. J.
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<strong>Selective knockout of mouse ERG1 B potassium channel eliminates I(Kr) in adult ventricular myocytes and elicits episodes of abrupt sinus bradycardia.</strong>
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Millat, G., Chevalier, P., Restier-Miron, L., Da Costa, A., Bouvagnet, P., Kugener, B., Fayol, L., Gonzalez Armengod, C., Oddou, B., Chanavat, V., Froidefond, E., Perraudin, R., Rousson, R., Rodriguez-Lafrasse, C.
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Moss, A. J., Zareba, W., Kaufman, E. S., Gartman, E., Peterson, D. R., Benhorin, J., Towbin, J. A., Keating, M. T., Priori, S. G., Schwartz, P. J., Vincent, G. M., Robinson, J. L., Andrews, M. L., Feng, C., Hall, W. J., Medina, A., Zhang, L., Wang, Z.
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<strong>Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel.</strong>
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Priori, S. G., Barhanin, J., Hauer, R. N. W., Haverkamp, W., Jongsma, H. J., Kleber, A. G., McKenna, W. J., Roden, D. M., Rudy, Y., Schwartz, K., Schwartz, P. J., Towbin, J. A., Wilde, A. M.
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Priori, S. G., Barhanin, J., Hauer, R. N. W., Haverkamp, W., Jongsma, H. J., Kleber, A. G., McKenna, W. J., Roden, D. M., Rudy, Y., Schwartz, K., Schwartz, P. J., Towbin, J. A., Wilde, A. M.
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Priori, S. G., Napolitano, C., Schwartz, P. J.
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<strong>Pharmacological rescue of human K+ channel long-QT2 mutations.</strong>
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Roden, D. M., Viswanathan, P. C.
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Sasano, T., McDonald, A. D., Kikuchi, K., Donahue, J. K.
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<strong>Molecular ablation of ventricular tachycardia after myocardial infarction.</strong>
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<p class="mim-text-font">
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Tester, D. J., Will, M. L., Haglund, C. M., Ackerman, M. J.
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<strong>Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.</strong>
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Heart Rhythm 2: 507-517, 2005.
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<li>
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<p class="mim-text-font">
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Zareba, W., Moss, A. J., Schwartz, P. J., Vincent, G. M., Robinson, J. L., Priori, S. G., Benhorin, J., Locati, E. H., Towbin, J. A., Keating, M. T., Lehmann, M. H., Hall, W. J., International Long-QT Syndrome Registry Research Group.
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<strong>Influence of the genotype on the clinical course of the long-QT syndrome.</strong>
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New Eng. J. Med. 339: 960-965, 1998.
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[PubMed: 9753711]
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[Full Text: https://doi.org/10.1056/NEJM199810013391404]
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<li>
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<p class="mim-text-font">
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Zhou, Z., Gong, Q., Epstein, M. L., January, C. T.
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<strong>HERG channel dysfunction in human long QT syndrome: intracellular transport and functional defects.</strong>
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J. Biol. Chem. 273: 21061-21066, 1998.
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[PubMed: 9694858]
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[Full Text: https://doi.org/10.1074/jbc.273.33.21061]
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<span class="mim-text-font">
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Ada Hamosh - updated : 6/14/2011
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Carol A. Bocchini : 1/13/2011
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