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<title>
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Entry
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- #603830 - LONG QT SYNDROME 3; LQT3
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- OMIM
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<span class="h4">#603830</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/603830"><strong>Clinical Synopsis</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="#clinicalFeatures">Clinical Features</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="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(LONG QT SYNDROME) OR (SCN5A)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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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 id="mimEuroGentestFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=14727&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Romano-Ward syndrome </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=658&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Familial long QT syndrome </a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1129/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/4301" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603830[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
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<div id="mimOrphanetFold" class="collapse">
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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 style="display: table-cell;">Animal Models</div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0110646" 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/603830" 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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<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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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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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> 0110646<br />
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">ICD+</a>
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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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603830
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</span>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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LONG QT SYNDROME 3; LQT3
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<div>
|
|
<br />
|
|
</div>
|
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|
|
<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
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<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<span class="h3 mim-font">
|
|
LONG QT SYNDROME 3, ACQUIRED, SUSCEPTIBILITY TO, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
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|
|
LONG QT SYNDROME 2/3, DIGENIC, INCLUDED; LQT2/3, DIGENIC, INCLUDED<br />
|
|
LONG QT SYNDROME 3/6, DIGENIC, INCLUDED; LQT3/6, DIGENIC, INCLUDED
|
|
</span>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
|
</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
|
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<th>
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|
Phenotype <br /> MIM number
|
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</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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<th>
|
|
Gene/Locus
|
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</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
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|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/3/181?start=-3&limit=10&highlight=181">
|
|
3p22.2
|
|
</a>
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Long QT syndrome 3
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603830"> 603830 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
SCN5A
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600163"> 600163 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
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|
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|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/603830" 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>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<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/603830" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/603830" 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>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
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|
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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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<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 /> -
|
|
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 /> -
|
|
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 /> -
|
|
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 />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
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|
|
|
|
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|
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|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Association of cardiac events with exercise<br /> -
|
|
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 /> -
|
|
Patients with 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 />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the sodium channel, voltage-gated, type V, alpha polypeptide gene (SCN5A, <a href="/entry/600163#0001">600163.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Long QT syndrome
|
|
- <a href="/phenotypicSeries/PS192500">PS192500</a>
|
|
- 21 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/236?start=-3&limit=10&highlight=236"> 2p21 </a>
|
|
|
|
</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"> 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/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/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"> Long QT syndrome 10 </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>
|
|
<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/11/1085?start=-3&limit=10&highlight=1085"> 11q24.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613485"> Long QT syndrome 13 </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/613485"> 613485 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600734"> KCNJ5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600734"> 600734 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/12/18?start=-3&limit=10&highlight=18"> 12p13.33 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618447"> Long QT syndrome 8 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/618447"> 618447 </a>
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<a href="/entry/114205"> CACNA1C </a>
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<span class="mim-font">
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<a href="/entry/114205"> 114205 </a>
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<a href="/geneMap/12/285?start=-3&limit=10&highlight=285"> 12q12 </a>
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<span class="mim-font">
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<a href="/entry/613688"> {Long QT syndrome, acquired, reduced susceptibility to} </a>
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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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<a href="/entry/613688"> 613688 </a>
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<a href="/entry/603313"> ALG10B </a>
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<a href="/entry/603313"> 603313 </a>
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<a href="/geneMap/14/455?start=-3&limit=10&highlight=455"> 14q32.11 </a>
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<span class="mim-font">
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<a href="/entry/616247"> Long QT syndrome 14 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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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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<a href="/entry/616247"> 616247 </a>
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<span class="mim-font">
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<a href="/entry/114180"> CALM1 </a>
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<span class="mim-font">
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<a href="/entry/114180"> 114180 </a>
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<a href="/geneMap/17/893?start=-3&limit=10&highlight=893"> 17q24.3 </a>
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<span class="mim-font">
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<a href="/entry/170390"> Andersen syndrome </a>
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<a href="/entry/170390"> 170390 </a>
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<a href="/entry/600681"> KCNJ2 </a>
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<a href="/entry/600681"> 600681 </a>
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<a href="/geneMap/19/854?start=-3&limit=10&highlight=854"> 19q13.32 </a>
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<span class="mim-font">
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<a href="/entry/618782"> ?Ventricular tachycardia, catecholaminergic polymorphic 6 </a>
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<span class="mim-font">
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/618782"> 618782 </a>
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<span class="mim-font">
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<a href="/entry/114183"> CALM3 </a>
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<span class="mim-font">
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<a href="/entry/114183"> 114183 </a>
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<a href="/geneMap/19/854?start=-3&limit=10&highlight=854"> 19q13.32 </a>
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</span>
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<span class="mim-font">
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<a href="/entry/618782"> Long QT syndrome 16 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/618782"> 618782 </a>
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<span class="mim-font">
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<a href="/entry/114183"> CALM3 </a>
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<span class="mim-font">
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<a href="/entry/114183"> 114183 </a>
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<a href="/geneMap/20/213?start=-3&limit=10&highlight=213"> 20q11.21 </a>
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<span class="mim-font">
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<a href="/entry/612955"> Long QT syndrome 12 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<span class="mim-font">
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<a href="/entry/612955"> 612955 </a>
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<span class="mim-font">
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<a href="/entry/601017"> SNTA1 </a>
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<span class="mim-font">
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<a href="/entry/601017"> 601017 </a>
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<a href="/geneMap/21/79?start=-3&limit=10&highlight=79"> 21q22.11 </a>
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</span>
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<td>
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<span class="mim-font">
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<a href="/entry/613693"> Long QT syndrome 6 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<span class="mim-font">
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<a href="/entry/613693"> 613693 </a>
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<span class="mim-font">
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<a href="/entry/603796"> KCNE2 </a>
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<span class="mim-font">
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<a href="/entry/603796"> 603796 </a>
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<span class="mim-font">
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<a href="/geneMap/21/80?start=-3&limit=10&highlight=80"> 21q22.12 </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/613695"> Long QT syndrome 5 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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<a href="/entry/613695"> 613695 </a>
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<span class="mim-font">
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<a href="/entry/176261"> KCNE1 </a>
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<span class="mim-font">
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<a href="/entry/176261"> 176261 </a>
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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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<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 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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<p>A number sign (#) is used with this entry because long QT syndrome-3 (LQT3) is caused by heterozygous mutation in the gene encoding the alpha polypeptide of voltage-gated sodium channel type V (SCN5A; <a href="/entry/600163">600163</a>) on chromosome 3p22.</p><p>Digenic inheritance has also been reported; see MOLECULAR GENETICS.</p>
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<a id="description" class="mim-anchor"></a>
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Description</strong>
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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="#4" 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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<strong>Clinical Features</strong>
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<p><a href="#11" class="mim-tip-reference" title="Wang, Q., Shen, J., Li, Z., Timothy, K., Vincent, G. M., Priori, S. G., Schwartz, P. J., Keating, M. T. <strong>Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia.</strong> Hum. Molec. Genet. 4: 1603-1607, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541846</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1603" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541846">Wang et al. (1995)</a> cited preliminary data suggesting that in chromosome 3-linked LQT the onset of the T wave is later and duration of the QT interval longer than in other forms. These data suggested to the authors that chromosome 3-linked LQT is more severe than the other forms. See GENOTYPE/PHENOTYPE CORRELATIONS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541846" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Molecular Genetics</strong>
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<p>The voltage-gated cardiac sodium channel SCN5A is responsible for the initial upstroke of the action potential in the electrocardiogram. <a href="#3" class="mim-tip-reference" title="George, A. L., Jr., Varkony, T. A., Drabkin, H. A., Han, J., Knops, J. F., Finley, W. H., Brown, G. B., Ward, D. C., Haas, M. <strong>Assignment of the human heart tetrodotoxin-resistant voltage-gated Na(+) channel alpha-subunit gene (SCN5A) to band 3p21.</strong> Cytogenet. Cell Genet. 68: 67-70, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7956363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7956363</a>] [<a href="https://doi.org/10.1159/000133892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7956363">George et al. (1995)</a> mapped SCN5A to 3p21 by fluorescence in situ hybridization, thus making it an important candidate gene for LQT3. Missense mutations in the skeletal muscle sodium channel gene, SCN4A (<a href="/entry/603967">603967</a>), cause myotonia. Physiologic data show that these mutations affect sodium channel inactivation and lead to repetitive depolarizations, consistent with the myotonic phenotype. By analogy, similar mutations in the cardiac sodium channel gene might be expected to cause a phenotype like LQT. Indeed, <a href="#12" class="mim-tip-reference" title="Wang, Q., Shen, J., Splawski, I., Atkinson, D., Li, Z., Robinson, J. L., Moss, A. J., Towbin, J. A., Keating, M. T. <strong>SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome.</strong> Cell 80: 805-811, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7889574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7889574</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90359-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7889574">Wang et al. (1995)</a> found a mutation in the SCN5A gene in families with chromosome 3-linked LQT (see <a href="/entry/600163#0001">600163.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7956363+7889574" 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="#11" class="mim-tip-reference" title="Wang, Q., Shen, J., Li, Z., Timothy, K., Vincent, G. M., Priori, S. G., Schwartz, P. J., Keating, M. T. <strong>Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia.</strong> Hum. Molec. Genet. 4: 1603-1607, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541846</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1603" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541846">Wang et al. (1995)</a> identified SCN5A mutations in affected members of 4 additional families with chromosome 3-linked LQT. Two of the families had the same 9-bp deletion found earlier; the other families were found to have missense mutations affecting highly conserved amino acid residues (<a href="/entry/600163#0002">600163.0002</a> and <a href="/entry/600163#0003">600163.0003</a>). The location and character of the mutation suggested to the authors that this form of LQT results from a delay in cardiac sodium channel fast inactivation or altered voltage-dependence of inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541846" 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 an 8-generation Dutch family with a history of sudden death, some members of which demonstrated ECG features compatible with Brugada syndrome (<a href="/entry/601144">601144</a>) and QT prolongation characteristic of long QT syndrome-3, <a href="#1" class="mim-tip-reference" title="Bezzina, C., Veldkamp, M. W., van den Berg, M. P., Postma, A. V., Rook, M. B., Viersma, J.-W., van Langen, I. M., Tan-Sindhunata, G., Bink-Boelkens, M. T. E., van der Hout, A. H., Mannens, M. M. A. M., Wilde, A. A. M. <strong>A single Na+ channel mutation causing both long-QT and Brugada syndromes.</strong> Circ. Res. 85: 1206-1213, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10590249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10590249</a>] [<a href="https://doi.org/10.1161/01.res.85.12.1206" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10590249">Bezzina et al. (1999)</a> detected an aberrant conformer corresponding to a novel mutation in the C terminal of the SCN5A protein (1795insD; <a href="/entry/600163#0013">600163.0013</a>). This family demonstrated that long QT syndrome-3 and Brugada syndrome appear to lie on a spectrum of cardiac electrophysiologic pathology caused by SCN5A mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10590249" 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="Veldkamp, M. W., Wilders, R., Baartscheer, A., Zegers, J. G., Bezzina, C. R., Wilde, A. A. M. <strong>Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families.</strong> Circ. Res. 92: 976-983, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12676817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12676817</a>] [<a href="https://doi.org/10.1161/01.RES.0000069689.09869.A8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12676817">Veldkamp et al. (2003)</a> studied the effect of the 1795insD mutation on sinoatrial (SA) pacemaking. Activity of 1795insD channels during SA node pacemaking was confirmed by action potential (AP) clamp experiments, and the previously characterized persistent inward current (I-pst) and negative shift were implemented into SA node (AP) models. The -10 mV shift decreased the sinus rate by decreasing the diastolic depolarization rate, whereas the I-pst decreased the sinus rate by AP prolongation, despite a concomitant increase in the diastolic depolarization rate. In combination, a moderate I-pst (1 to 2%) and the shift reduced the sinus rate by about 10%. <a href="#10" class="mim-tip-reference" title="Veldkamp, M. W., Wilders, R., Baartscheer, A., Zegers, J. G., Bezzina, C. R., Wilde, A. A. M. <strong>Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families.</strong> Circ. Res. 92: 976-983, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12676817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12676817</a>] [<a href="https://doi.org/10.1161/01.RES.0000069689.09869.A8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12676817">Veldkamp et al. (2003)</a> concluded that sodium channel mutations displaying an I-pst or a negative shift in inactivation may account for the bradycardia seen in LQT3 patients, whereas SA node pauses or arrest may result from failure of SA node cells to repolarize under conditions of extra net inward current. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12676817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with long QT syndrome-3, <a href="#8" class="mim-tip-reference" title="Rivolta, I., Abriel, H., Tateyama, M., Liu, H., Memmi, M., Vardas, P., Napolitano, C., Priori, S. G., Kass, R. S. <strong>Inherited Brugada and long QT-3 syndrome mutations of a single channel residue of the cardiac sodium channel confer distinct channel and clinical phenotypes.</strong> J. Biol. Chem. 276: 30623-30630, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11410597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11410597</a>] [<a href="https://doi.org/10.1074/jbc.M104471200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11410597">Rivolta et al. (2001)</a> identified a tyr1795-to-cys mutation in the SCN5A gene (Y1795C; <a href="/entry/600163#0029">600163.0029</a>). In a patient with Brugada syndrome, they identified a different mutation at the same codon (Y1795H; <a href="/entry/600163#0030">600163.0030</a>). They concluded that these findings provided further evidence of the close interrelationship between Brugada syndrome and long QT syndrome-3 at the molecular level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11410597" 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="#2" class="mim-tip-reference" title="Clancy, C. E., Tateyama, M., Kass, R. S. <strong>Insights into the molecular mechanisms of bradycardia-triggered arrhythmias in long QT-3 syndrome.</strong> J. Clin. Invest. 110: 1251-1262, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12417563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12417563</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12417563[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/JCI15928" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12417563">Clancy et al. (2002)</a> performed detailed kinetic analyses of the Y1795C mutant described by <a href="#8" class="mim-tip-reference" title="Rivolta, I., Abriel, H., Tateyama, M., Liu, H., Memmi, M., Vardas, P., Napolitano, C., Priori, S. G., Kass, R. S. <strong>Inherited Brugada and long QT-3 syndrome mutations of a single channel residue of the cardiac sodium channel confer distinct channel and clinical phenotypes.</strong> J. Biol. Chem. 276: 30623-30630, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11410597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11410597</a>] [<a href="https://doi.org/10.1074/jbc.M104471200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11410597">Rivolta et al. (2001)</a>. Theoretical entry and exit rates from the bursting mode of gating were derived from single channels. Computational analysis suggested that the amount of time mutant channels spend bursting (burst mode dwell time) is primarily responsible for rate-dependent changes in single-channel bursting and macroscopic inward sodium channel (I-sus), hence delaying repolarization and prolonging the QT interval. This prediction was experimentally confirmed by analysis of delta-KPQ mutant channels (<a href="/entry/600163#0001">600163.0001</a>) for which the burst mode exit rate (determined by the burst mode dwell time) was found to be very similar to the derived rate for Y1795C channels. These results provided an explanation of the molecular mechanism for bradycardia-induced QT prolongation in patients carrying LQT3 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11410597+12417563" 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 male infant diagnosed with ventricular arrhythmias and cardiac decompensation in utero at 28 weeks' gestation and with LQT3 at birth, <a href="#7" class="mim-tip-reference" title="Miller, T. E., Estrella, E., Myerburg, R. J., Garcia de Viera, J., Moreno, N., Rusconi, P., Ahearn, M. E., Baumbach, L., Kurlansky, P., Wolff, G., Bishopric, N. H. <strong>Recurrent third-trimester fetal loss and maternal mosaicism for long-QT syndrome.</strong> Circulation 109: 3029-3034, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15184283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15184283</a>] [<a href="https://doi.org/10.1161/01.CIR.0000130666.81539.9E" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15184283">Miller et al. (2004)</a> identified heterozygosity for a mutation in the SCN5A gene (R1623Q; <a href="/entry/600163#0007">600163.0007</a>). The patient required cardiac transplantation at 5 months of age for control of ventricular tachycardia. The mother had no ECG abnormalities, but a previous and a subsequent pregnancy had both ended in stillbirth at 7 months. Initial studies detected no genetic abnormality, but a sensitive restriction enzyme-based assay revealed a small percentage (8 to 10%) of cells harboring the mutation in the mother's blood, skin, and buccal mucosa; the mutation was also identified in cord blood from the third fetus. <a href="#7" class="mim-tip-reference" title="Miller, T. E., Estrella, E., Myerburg, R. J., Garcia de Viera, J., Moreno, N., Rusconi, P., Ahearn, M. E., Baumbach, L., Kurlansky, P., Wolff, G., Bishopric, N. H. <strong>Recurrent third-trimester fetal loss and maternal mosaicism for long-QT syndrome.</strong> Circulation 109: 3029-3034, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15184283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15184283</a>] [<a href="https://doi.org/10.1161/01.CIR.0000130666.81539.9E" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15184283">Miller et al. (2004)</a> concluded that recurrent late-term fetal loss or sudden infant death can result from unsuspected parental mosaicism for LQT-associated mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15184283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="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 (<a href="/entry/607542">607542</a>), 89 in KCNH2 (<a href="/entry/152427">152427</a>), 32 in SCN5A, and 1 each in KCNE1 (<a href="/entry/176261">176261</a>) and KCNE2 (<a href="/entry/603796">603796</a>). 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="#9" 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="#6" 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/600163#0007">600163.0007</a> and <a href="/entry/600163#0035">600163.0035</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><a href="#5" class="mim-tip-reference" title="Makita, N., Behr, E., Shimizu, W., Horie, M., Sunami, A., Crotti, L., Schulze-Bahr, E., Fukuhara, S., Mochizuki, N., Makiyama, T., Itoh, H., Christiansen, M., McKeown, P., Miyamoto, K., Kamakura, S., Tsutsui, H., Schwartz, P. J., George, A. L., Jr., Roden, D. M. <strong>The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome.</strong> J. Clin. Invest. 118: 2219-2229, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18451998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18451998</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18451998[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/JCI34057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18451998">Makita et al. (2008)</a> genotyped 66 members of 44 LQT3 families of multiple ethnicities and identified the E1784K mutation in the SCN5A gene (<a href="/entry/600163#0008">600163.0008</a>) in 41 individuals from 15 (34%) of the kindreds; the diagnoses in these individuals included LQT3 syndrome, Brugada syndrome (<a href="/entry/601144">601144</a>), and/or sinus node dysfunction (see <a href="/entry/608567">608567</a>). In vitro functional characterization of E1784K compared to properties reported for other LQT3 variants suggested that a negative shift of steady-state Na channel inactivation and enhanced tonic block in response to Na channel blockers represent common biophysical mechanisms underlying the phenotypic overlap of LQT3 and Brugada syndromes, and further indicated that class IC drugs should be avoided in patients with Na channels displaying these behaviors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18451998" 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="#9" 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). 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="#9" 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="#6" 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/600163#0007">600163.0007</a> and <a href="/entry/600163#0035">600163.0035</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>
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<p>In a large collaborative study, <a href="#14" 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> demonstrated that the genotype of the long QT syndrome influences the clinical course. The risk of cardiac events (syncope, aborted cardiac arrest, or sudden death) was significantly higher among subjects with mutations at the LQT1 (<a href="/entry/192500">192500</a>) locus (KCNQ1; <a href="/entry/607542">607542</a>) or the LQT2 (<a href="/entry/613688">613688</a>) locus (KCNH2; <a href="/entry/152427">152427</a>) than among those with mutations at the LQT3 locus. Although the cumulative mortality was similar regardless of the genotype, the percentage of cardiac events that were lethal was significantly higher in families with mutations at the LQT3 locus. In this large study, 112 patients had mutations at the LQT1 locus, 72 at the LQT2 locus, and 62 at the LQT3 locus. Thus, paradoxically, cardiac events were less frequent in LQT3 but more likely to be lethal; the likelihood of dying during a cardiac event was 20% in families with an LQT3 mutation and 4% with either an LQT1 or an LQT2 mutation. <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="#13" class="mim-tip-reference" title="Westenskow, P., Splawski, I., Timothy, K. W., Keating, M. T., Sanguinetti, M. C. <strong>Compound mutations: a common cause of severe long-QT syndrome.</strong> Circulation 109: 1834-1841, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15051636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15051636</a>] [<a href="https://doi.org/10.1161/01.CIR.0000125524.34234.13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15051636">Westenskow et al. (2004)</a> analyzed the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes in 252 probands with long QT syndrome and identified 19 with biallelic mutations in LQTS genes, of whom 18 were either compound (monogenic) or double (digenic) heterozygotes and 1 was a homozygote. They also identified 1 patient who had triallelic digenic mutations (see <a href="/entry/152427#0021">152427.0021</a>). Compared with probands who had 1 or no identified mutation, probands with 2 mutations had longer QTc intervals (p less than 0.001) and were 3.5-fold more likely to undergo cardiac arrest (p less than 0.01). All 20 probands with 2 mutations had experienced cardiac events. <a href="#13" class="mim-tip-reference" title="Westenskow, P., Splawski, I., Timothy, K. W., Keating, M. T., Sanguinetti, M. C. <strong>Compound mutations: a common cause of severe long-QT syndrome.</strong> Circulation 109: 1834-1841, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15051636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15051636</a>] [<a href="https://doi.org/10.1161/01.CIR.0000125524.34234.13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15051636">Westenskow et al. (2004)</a> concluded that biallelic mono- or digenic mutations (which the authors termed 'compound mutations') cause a severe phenotype and are relatively common in long QT syndrome. The authors noted that these findings support the concept of arrhythmia risk as a multi-hit process and suggested that genotype can be used to predict risk. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15051636" 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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Bezzina, C., Veldkamp, M. W., van den Berg, M. P., Postma, A. V., Rook, M. B., Viersma, J.-W., van Langen, I. M., Tan-Sindhunata, G., Bink-Boelkens, M. T. E., van der Hout, A. H., Mannens, M. M. A. M., Wilde, A. A. M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10590249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10590249</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10590249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1161/01.res.85.12.1206" target="_blank">Full Text</a>]
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Clancy, C. E., Tateyama, M., Kass, R. S.
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J. Clin. Invest. 110: 1251-1262, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12417563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12417563</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12417563[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12417563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI15928" target="_blank">Full Text</a>]
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George, A. L., Jr., Varkony, T. A., Drabkin, H. A., Han, J., Knops, J. F., Finley, W. H., Brown, G. B., Ward, D. C., Haas, M.
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<strong>Assignment of the human heart tetrodotoxin-resistant voltage-gated Na(+) channel alpha-subunit gene (SCN5A) to band 3p21.</strong>
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Cytogenet. Cell Genet. 68: 67-70, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7956363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7956363</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7956363" 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/10.1159/000133892" target="_blank">Full Text</a>]
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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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<strong>Novel KCNQ1 and HERG missense mutations in Dutch long-QT families.</strong>
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Hum. Mutat. 13: 301-310, 1999.
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[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://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'})">related citations</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)13:4<301::AID-HUMU7>3.0.CO;2-V" target="_blank">Full Text</a>]
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Makita, N., Behr, E., Shimizu, W., Horie, M., Sunami, A., Crotti, L., Schulze-Bahr, E., Fukuhara, S., Mochizuki, N., Makiyama, T., Itoh, H., Christiansen, M., McKeown, P., Miyamoto, K., Kamakura, S., Tsutsui, H., Schwartz, P. J., George, A. L., Jr., Roden, D. M.
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<strong>The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome.</strong>
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J. Clin. Invest. 118: 2219-2229, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18451998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18451998</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18451998[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18451998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI34057" target="_blank">Full Text</a>]
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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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<strong>Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.</strong>
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Clin. Genet. 70: 214-227, 2006.
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[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://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'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2006.00671.x" target="_blank">Full Text</a>]
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Miller, T. E., Estrella, E., Myerburg, R. J., Garcia de Viera, J., Moreno, N., Rusconi, P., Ahearn, M. E., Baumbach, L., Kurlansky, P., Wolff, G., Bishopric, N. H.
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<strong>Recurrent third-trimester fetal loss and maternal mosaicism for long-QT syndrome.</strong>
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Circulation 109: 3029-3034, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15184283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15184283</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15184283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1161/01.CIR.0000130666.81539.9E" target="_blank">Full Text</a>]
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Rivolta, I., Abriel, H., Tateyama, M., Liu, H., Memmi, M., Vardas, P., Napolitano, C., Priori, S. G., Kass, R. S.
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<strong>Inherited Brugada and long QT-3 syndrome mutations of a single channel residue of the cardiac sodium channel confer distinct channel and clinical phenotypes.</strong>
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J. Biol. Chem. 276: 30623-30630, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11410597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11410597</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11410597" 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.M104471200" target="_blank">Full Text</a>]
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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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[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://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'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.hrthm.2005.01.020" target="_blank">Full Text</a>]
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<a id="Veldkamp2003" class="mim-anchor"></a>
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Veldkamp, M. W., Wilders, R., Baartscheer, A., Zegers, J. G., Bezzina, C. R., Wilde, A. A. M.
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<strong>Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families.</strong>
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Circ. Res. 92: 976-983, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12676817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12676817</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12676817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1161/01.RES.0000069689.09869.A8" target="_blank">Full Text</a>]
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<a id="Wang1995" class="mim-anchor"></a>
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Wang, Q., Shen, J., Li, Z., Timothy, K., Vincent, G. M., Priori, S. G., Schwartz, P. J., Keating, M. T.
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<strong>Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia.</strong>
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Hum. Molec. Genet. 4: 1603-1607, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541846</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541846" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/4.9.1603" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Wang1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, Q., Shen, J., Splawski, I., Atkinson, D., Li, Z., Robinson, J. L., Moss, A. J., Towbin, J. A., Keating, M. T.
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<strong>SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome.</strong>
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Cell 80: 805-811, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7889574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7889574</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7889574" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0092-8674(95)90359-3" target="_blank">Full Text</a>]
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<a id="Westenskow2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Westenskow, P., Splawski, I., Timothy, K. W., Keating, M. T., Sanguinetti, M. C.
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<strong>Compound mutations: a common cause of severe long-QT syndrome.</strong>
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Circulation 109: 1834-1841, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15051636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15051636</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15051636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1161/01.CIR.0000125524.34234.13" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Zareba1998" class="mim-anchor"></a>
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<div class="">
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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: <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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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 12/23/2008
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 2/26/2008<br>Marla J. F. O'Neill - updated : 11/9/2006<br>Marla J. F. O'Neill - updated : 1/31/2006<br>Marla J. F. O'Neill - updated : 3/16/2004<br>Marla J. F. O'Neill - updated : 2/18/2004<br>Denise L. M. Goh - updated : 1/6/2003<br>Paul Brennan - updated : 4/3/2000
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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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Victor A. McKusick : 5/24/1999
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carol : 04/24/2017
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<span class="mim-text-font">
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carol : 04/23/2017<br>carol : 09/18/2015<br>alopez : 6/12/2014<br>alopez : 2/2/2012<br>alopez : 2/2/2012<br>carol : 1/13/2011<br>carol : 1/13/2011<br>carol : 6/23/2009<br>carol : 12/24/2008<br>terry : 12/23/2008<br>wwang : 2/26/2008<br>carol : 11/16/2006<br>carol : 11/9/2006<br>carol : 11/9/2006<br>wwang : 2/3/2006<br>terry : 1/31/2006<br>tkritzer : 3/18/2004<br>tkritzer : 3/16/2004<br>carol : 2/18/2004<br>carol : 2/5/2003<br>carol : 1/6/2003<br>carol : 1/6/2003<br>alopez : 4/3/2000<br>carol : 7/7/1999<br>carol : 5/25/1999
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<span class="mim-font">
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<strong>#</strong> 603830
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LONG QT SYNDROME 3; LQT3
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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 3, ACQUIRED, SUSCEPTIBILITY TO, 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 3/6, DIGENIC, INCLUDED; LQT3/6, DIGENIC, INCLUDED
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<strong>ORPHA:</strong> 101016, 768;
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<strong>DO:</strong> 0110646;
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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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<thead>
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Location
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<th>
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Phenotype
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<th>
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Phenotype <br /> MIM number
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<th>
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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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3p22.2
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<span class="mim-font">
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Long QT syndrome 3
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<span class="mim-font">
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603830
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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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SCN5A
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<span class="mim-font">
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600163
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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-3 (LQT3) is caused by heterozygous mutation in the gene encoding the alpha polypeptide of voltage-gated sodium channel type V (SCN5A; 600163) on chromosome 3p22.</p><p>Digenic inheritance has also been reported; see MOLECULAR GENETICS.</p>
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<strong>Description</strong>
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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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<strong>Clinical Features</strong>
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<p>Wang et al. (1995) cited preliminary data suggesting that in chromosome 3-linked LQT the onset of the T wave is later and duration of the QT interval longer than in other forms. These data suggested to the authors that chromosome 3-linked LQT is more severe than the other forms. See GENOTYPE/PHENOTYPE CORRELATIONS. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>The voltage-gated cardiac sodium channel SCN5A is responsible for the initial upstroke of the action potential in the electrocardiogram. George et al. (1995) mapped SCN5A to 3p21 by fluorescence in situ hybridization, thus making it an important candidate gene for LQT3. Missense mutations in the skeletal muscle sodium channel gene, SCN4A (603967), cause myotonia. Physiologic data show that these mutations affect sodium channel inactivation and lead to repetitive depolarizations, consistent with the myotonic phenotype. By analogy, similar mutations in the cardiac sodium channel gene might be expected to cause a phenotype like LQT. Indeed, Wang et al. (1995) found a mutation in the SCN5A gene in families with chromosome 3-linked LQT (see 600163.0001). </p><p>Wang et al. (1995) identified SCN5A mutations in affected members of 4 additional families with chromosome 3-linked LQT. Two of the families had the same 9-bp deletion found earlier; the other families were found to have missense mutations affecting highly conserved amino acid residues (600163.0002 and 600163.0003). The location and character of the mutation suggested to the authors that this form of LQT results from a delay in cardiac sodium channel fast inactivation or altered voltage-dependence of inactivation. </p><p>In an 8-generation Dutch family with a history of sudden death, some members of which demonstrated ECG features compatible with Brugada syndrome (601144) and QT prolongation characteristic of long QT syndrome-3, Bezzina et al. (1999) detected an aberrant conformer corresponding to a novel mutation in the C terminal of the SCN5A protein (1795insD; 600163.0013). This family demonstrated that long QT syndrome-3 and Brugada syndrome appear to lie on a spectrum of cardiac electrophysiologic pathology caused by SCN5A mutation. </p><p>Veldkamp et al. (2003) studied the effect of the 1795insD mutation on sinoatrial (SA) pacemaking. Activity of 1795insD channels during SA node pacemaking was confirmed by action potential (AP) clamp experiments, and the previously characterized persistent inward current (I-pst) and negative shift were implemented into SA node (AP) models. The -10 mV shift decreased the sinus rate by decreasing the diastolic depolarization rate, whereas the I-pst decreased the sinus rate by AP prolongation, despite a concomitant increase in the diastolic depolarization rate. In combination, a moderate I-pst (1 to 2%) and the shift reduced the sinus rate by about 10%. Veldkamp et al. (2003) concluded that sodium channel mutations displaying an I-pst or a negative shift in inactivation may account for the bradycardia seen in LQT3 patients, whereas SA node pauses or arrest may result from failure of SA node cells to repolarize under conditions of extra net inward current. </p><p>In a patient with long QT syndrome-3, Rivolta et al. (2001) identified a tyr1795-to-cys mutation in the SCN5A gene (Y1795C; 600163.0029). In a patient with Brugada syndrome, they identified a different mutation at the same codon (Y1795H; 600163.0030). They concluded that these findings provided further evidence of the close interrelationship between Brugada syndrome and long QT syndrome-3 at the molecular level. </p><p>Clancy et al. (2002) performed detailed kinetic analyses of the Y1795C mutant described by Rivolta et al. (2001). Theoretical entry and exit rates from the bursting mode of gating were derived from single channels. Computational analysis suggested that the amount of time mutant channels spend bursting (burst mode dwell time) is primarily responsible for rate-dependent changes in single-channel bursting and macroscopic inward sodium channel (I-sus), hence delaying repolarization and prolonging the QT interval. This prediction was experimentally confirmed by analysis of delta-KPQ mutant channels (600163.0001) for which the burst mode exit rate (determined by the burst mode dwell time) was found to be very similar to the derived rate for Y1795C channels. These results provided an explanation of the molecular mechanism for bradycardia-induced QT prolongation in patients carrying LQT3 mutations. </p><p>In a male infant diagnosed with ventricular arrhythmias and cardiac decompensation in utero at 28 weeks' gestation and with LQT3 at birth, Miller et al. (2004) identified heterozygosity for a mutation in the SCN5A gene (R1623Q; 600163.0007). The patient required cardiac transplantation at 5 months of age for control of ventricular tachycardia. The mother had no ECG abnormalities, but a previous and a subsequent pregnancy had both ended in stillbirth at 7 months. Initial studies detected no genetic abnormality, but a sensitive restriction enzyme-based assay revealed a small percentage (8 to 10%) of cells harboring the mutation in the mother's blood, skin, and buccal mucosa; the mutation was also identified in cord blood from the third fetus. Miller et al. (2004) concluded that recurrent late-term fetal loss or sudden infant death can result from unsuspected parental mosaicism for LQT-associated mutations. </p><p>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 (607542), 89 in KCNH2 (152427), 32 in SCN5A, and 1 each in KCNE1 (176261) and KCNE2 (603796). 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., 600163.0007 and 600163.0035). </p><p>Makita et al. (2008) genotyped 66 members of 44 LQT3 families of multiple ethnicities and identified the E1784K mutation in the SCN5A gene (600163.0008) in 41 individuals from 15 (34%) of the kindreds; the diagnoses in these individuals included LQT3 syndrome, Brugada syndrome (601144), and/or sinus node dysfunction (see 608567). In vitro functional characterization of E1784K compared to properties reported for other LQT3 variants suggested that a negative shift of steady-state Na channel inactivation and enhanced tonic block in response to Na channel blockers represent common biophysical mechanisms underlying the phenotypic overlap of LQT3 and Brugada syndromes, and further indicated that class IC drugs should be avoided in patients with Na channels displaying these behaviors. </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). 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., 600163.0007 and 600163.0035). </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>In a large collaborative study, Zareba et al. (1998) demonstrated that the genotype of the long QT syndrome influences the clinical course. The risk of cardiac events (syncope, aborted cardiac arrest, or sudden death) was significantly higher among subjects with mutations at the LQT1 (192500) locus (KCNQ1; 607542) or the LQT2 (613688) locus (KCNH2; 152427) than among those with mutations at the LQT3 locus. Although the cumulative mortality was similar regardless of the genotype, the percentage of cardiac events that were lethal was significantly higher in families with mutations at the LQT3 locus. In this large study, 112 patients had mutations at the LQT1 locus, 72 at the LQT2 locus, and 62 at the LQT3 locus. Thus, paradoxically, cardiac events were less frequent in LQT3 but more likely to be lethal; the likelihood of dying during a cardiac event was 20% in families with an LQT3 mutation and 4% with either an LQT1 or an LQT2 mutation. </p><p>Westenskow et al. (2004) analyzed the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes in 252 probands with long QT syndrome and identified 19 with biallelic mutations in LQTS genes, of whom 18 were either compound (monogenic) or double (digenic) heterozygotes and 1 was a homozygote. They also identified 1 patient who had triallelic digenic mutations (see 152427.0021). Compared with probands who had 1 or no identified mutation, probands with 2 mutations had longer QTc intervals (p less than 0.001) and were 3.5-fold more likely to undergo cardiac arrest (p less than 0.01). All 20 probands with 2 mutations had experienced cardiac events. Westenskow et al. (2004) concluded that biallelic mono- or digenic mutations (which the authors termed 'compound mutations') cause a severe phenotype and are relatively common in long QT syndrome. The authors noted that these findings support the concept of arrhythmia risk as a multi-hit process and suggested that genotype can be used to predict risk. </p>
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Westenskow, P., Splawski, I., Timothy, K. W., Keating, M. T., Sanguinetti, M. C.
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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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Marla J. F. O'Neill - updated : 12/23/2008<br>Marla J. F. O'Neill - updated : 2/26/2008<br>Marla J. F. O'Neill - updated : 11/9/2006<br>Marla J. F. O'Neill - updated : 1/31/2006<br>Marla J. F. O'Neill - updated : 3/16/2004<br>Marla J. F. O'Neill - updated : 2/18/2004<br>Denise L. M. Goh - updated : 1/6/2003<br>Paul Brennan - updated : 4/3/2000
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NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
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OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
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