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Entry
- #176670 - HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS
- OMIM
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<span class="h4">#176670</span>
<br />
<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/176670"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS176670"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#cytogenetics">Cytogenetics</a>
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<a href="#populationGenetics">Population Genetics</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="#pathogenesis">Pathogenesis</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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<div><a href="https://clinicaltrials.gov/search?cond=HUTCHINSON-GILFORD PROGERIA SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1121/" 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.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=740" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/c1fc8e60-b051-4f08-951f-96100c952901/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:3911" 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>
<div><a href="http://www.informatics.jax.org/disease/176670" 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>
<div><a href="https://omia.org/OMIA001213/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:3911" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:176670" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<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.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 238870004<br />
<strong>ICD10CM:</strong> E34.8<br />
<strong>ORPHA:</strong> 740<br />
<strong>DO:</strong> 3911<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
176670
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
PROGERIA
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="includedTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
PROGERIA SYNDROME, CHILDHOOD-ONSET, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1240?start=-3&limit=10&highlight=1240">
1q22
</a>
</span>
</td>
<td>
<span class="mim-font">
Hutchinson-Gilford progeria
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176670"> 176670 </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">
LMNA
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/150330"> 150330 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/176670" 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>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS176670" 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>
&nbsp;
<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/176670" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/176670" 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>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<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> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Weight </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Normal birth weight <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276712009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276712009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0456136&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456136</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Prominent scalp veins <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856542&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856542</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001043" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001043</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001043" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001043</a>]</span><br /> -
Delayed closure of fontanel <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/82779003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">82779003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0277828&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0277828</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000270</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000270</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Craniofacial disproportion <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867114&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867114</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005461" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005461</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005461" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005461</a>]</span><br /> -
Micrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32958008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32958008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.04</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Micrognathia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Retrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109515000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109515000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035353&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035353</a>, <a href="https://bioportal.bioontology.org/search?q=C3494422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3494422</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000278</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000278</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=ede3aa3495baae8accf26d8f779302ba" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Retrognathia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=ede3aa3495baae8accf26d8f779302ba&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Conductive hearing loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44057004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44057004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018777&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018777</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000405" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000405</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000405" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000405</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sparse eyebrows <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422441003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422441003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0578682&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0578682</a>, <a href="https://bioportal.bioontology.org/search?q=C1832446&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1832446</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002223" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002223</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0045075" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045075</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0045075" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045075</a>]</span><br /> -
Sparse eyelashes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843300&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843300</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000653" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000653</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000653" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000653</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=09052e490ffb13e8a17a589d4a9208f0" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eyelashes,Sparse-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=09052e490ffb13e8a17a589d4a9208f0&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Prominent eyes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837760&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837760</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000520" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000520</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000520" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000520</a>]</span><br /> -
Farsightedness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38101003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38101003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H52.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H52.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/367.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">367.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020490&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020490</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span><br /> -
Nocturnal lagophthalmos <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/417740005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">417740005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1563118&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1563118</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030002</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030002</a>]</span><br /> -
Corneal dryness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542245&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542245</a>]</span><br /> -
Exposure keratitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14366000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14366000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H16.21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H16.21</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/370.34" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">370.34</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0339295&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0339295</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Narrow nasal bridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551564&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551564</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000446" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000446</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000446" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000446</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=4851b8e2f8e95412788215794870d541" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Narrow-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=4851b8e2f8e95412788215794870d541&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Broad nasal tip <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249327002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249327002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426429&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426429</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000455" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000455</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000455" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000455</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6ddac380d031baefd82dea5c5d13ca2a" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Tip,Broad-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=6ddac380d031baefd82dea5c5d13ca2a&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Circumoral cyanosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1262254&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1262254</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032556" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032556</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032556" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032556</a>]</span><br /> -
Ankyloglossia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/67787004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">67787004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/750.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">750.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152415&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152415</a>, <a href="https://bioportal.bioontology.org/search?q=C4759698&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4759698</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010296" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010296</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010296" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010296</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9ef931b279ada8cf9e68129bb3f83b52" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Ankyloglossia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9ef931b279ada8cf9e68129bb3f83b52&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Ogival palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27272007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27272007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240635&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240635</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Delayed tooth eruption <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5639000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5639000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239174&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239174</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000684" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000684</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000684" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000684</a>]</span><br /> -
Hypodontia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64969001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64969001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K00.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K00.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020608&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020608</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000668" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000668</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000668" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000668</a>]</span><br /> -
Dental crowding <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12351004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12351004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.31</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040433&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040433</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000678" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000678</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000678" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000678</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=bc1fcb988aa10dd9d5f3774c342364a9" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Dental_Crowding-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=bc1fcb988aa10dd9d5f3774c342364a9&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</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">
- Angina <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/194828000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">194828000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/225566008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">225566008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I20.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I20.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/413" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">413</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2024883&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2024883</a>, <a href="https://bioportal.bioontology.org/search?q=C0002962&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002962</a>, <a href="https://bioportal.bioontology.org/search?q=C2926611&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2926611</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001681" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001681</a>]</span><br /> -
Myocardial infarction <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22298006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22298006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I22</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I21</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2926063&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2926063</a>, <a href="https://bioportal.bioontology.org/search?q=C0027051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001658" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001658</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001658" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001658</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Vascular </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Premature atherosclerosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4021654&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4021654</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004416" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004416</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004416" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004416</a>]</span><br /> -
Elevated systolic blood pressure <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840374&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840374</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004421" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004421</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004421" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004421</a>]</span><br /> -
Elevated diastolic blood pressure <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840375&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840375</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005117" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005117</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005117" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005117</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CHEST </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Ribs Sternum Clavicles & Scapulae </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Lateral clavicle resorption <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542244&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542244</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Osteopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/312894000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">312894000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029453&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029453</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000938" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000938</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000938" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000938</a>]</span><br /> -
Osteoporosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64859006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64859006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Z82.62" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Z82.62</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M81.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M81.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/733.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">733.0</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/V17.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">V17.81</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/733.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">733.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2911643&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2911643</a>, <a href="https://bioportal.bioontology.org/search?q=C0029456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029456</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000939" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000939</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000939" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000939</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Skull </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thin calvarium <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010539" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010539</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010539" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010539</a>]</span><br /> -
Delayed closure of anterior and posterior fontanel <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542246&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542246</a>]</span><br /> -
Widened sutures <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845802&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845802</a>]</span><br /> -
Bitemporal bossing <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542247&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542247</a>]</span><br /> -
Hypoplastic mandible <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32958008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32958008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.04</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Ovoid vertebrae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855665&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855665</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003300</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003300</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Pelvis </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Coxa valga <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33754009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33754009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16979000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16979000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299236004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299236004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q65.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q65.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/755.61" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">755.61</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/736.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.31</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158480&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158480</a>, <a href="https://bioportal.bioontology.org/search?q=C0152430&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152430</a>, <a href="https://bioportal.bioontology.org/search?q=C0239137&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239137</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002673" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002673</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002673" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002673</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Genu valgum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299330008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299330008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52012001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52012001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.06" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.06</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/736.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158484&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158484</a>, <a href="https://bioportal.bioontology.org/search?q=C0576093&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576093</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002857" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002857</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002857" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002857</a>]</span><br /> -
Flexion contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88565003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88565003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/203598005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">203598005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/785817002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">785817002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/385522000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">385522000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0333068&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0333068</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001371</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001371</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Distal phalangeal tufting <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542248&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542248</a>]</span><br /> -
Phalangeal contractures <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542249&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542249</a>]</span><br /> -
Acroosteolysis of distal phalanges <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849547&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849547</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009839" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009839</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009839" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009839</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Calcaneovalgus <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860450&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860450</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001848" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001848</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001848" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001848</a>]</span><br /> -
Acroosteolysis of distal phalanges <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849547&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849547</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009839" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009839</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009839" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009839</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sclerodermatous skin changes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859639&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859639</a>]</span><br /> -
Skin dimpling <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/301854006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">301854006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0578531&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0578531</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010781" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010781</a>]</span><br /> -
Skin mottling <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/112623001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">112623001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/406128001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">406128001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0302133&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0302133</a>]</span><br /> -
Prominent cutaneous vasculature <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542250&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542250</a>]</span><br /> -
Skin hyperpigmentation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4830009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4830009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/49765009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">49765009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0162834&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162834</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000953" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000953</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000953" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000953</a>]</span><br /> -
Skin hypopigmentation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/18655006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">18655006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/23006000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">23006000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/89031001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">89031001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0162835&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162835</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001010" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001010</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001010" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001010</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nails </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short nails <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247488004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247488004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423808&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423808</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001799" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001799</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001799" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001799</a>]</span><br /> -
Dystrophic nails <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87065009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87065009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L60.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L60.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221260</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008404</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008404</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hair </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Alopecia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278040002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278040002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56317004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56317004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L65.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L65.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/704.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">704.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/704.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">704.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002170&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002170</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001596" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001596</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002293</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001596" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001596</a>]</span><br /> -
Sparse eyebrows <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422441003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422441003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0578682&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0578682</a>, <a href="https://bioportal.bioontology.org/search?q=C1832446&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1832446</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002223" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002223</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0045075" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045075</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0045075" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045075</a>]</span><br /> -
Sparse eyelashes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843300&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843300</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000653" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000653</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000653" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000653</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=09052e490ffb13e8a17a589d4a9208f0" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eyelashes,Sparse-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=09052e490ffb13e8a17a589d4a9208f0&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Lipodystrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71325002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71325002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E88.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E88.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/272.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">272.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023787&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023787</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009125" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009125</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009125" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009125</a>]</span><br /> -
Muscular atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88092000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88092000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541794&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541794</a>, <a href="https://bioportal.bioontology.org/search?q=C0026846&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026846</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Transient ischemic attacks (TIAs) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/266257000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">266257000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G45.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G45.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007787&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007787</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002326" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002326</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002326" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002326</a>]</span><br /> -
Stroke <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230690007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230690007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I63.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I63.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038454&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038454</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001297</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001297</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Insulin resistance <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48606007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48606007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/763325000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">763325000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0021655&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0021655</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000855" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000855</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000855" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000855</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Elevated platelet count <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/6631009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">6631009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415115007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415115007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D75.839" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D75.839</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D75.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D75.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0857460&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0857460</a>, <a href="https://bioportal.bioontology.org/search?q=C0836924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0836924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001894" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001894</a>]</span><br /> -
Prolonged prothrombin time <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409674002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409674002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/313341008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">313341008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151872&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151872</a>, <a href="https://bioportal.bioontology.org/search?q=C0853225&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853225</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008151</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008151</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Aminoaciduria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35912001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35912001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238621&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238621</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003355</a>]</span><br /> -
Elevated serum phosphorus <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850137&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850137</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Premature aging <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88587007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88587007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399959003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399959003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231341&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231341</a>]</span><br /> -
Paternal age effect<br /> -
Median age of clinical diagnosis 19 months (in most patients)<br /> -
Median life expectancy 13 years (in most patients)<br /> -
Majority of classic cases have a single de novo mutation (GLY608GLY, <a href="/entry/150330#0022">150330.0022</a>)<br /> -
Some patients have an atypical phenotype with a later age at diagnosis and more protracted disease course<br /> -
Somatic mosaicism and apparent germline mosaicism have been reported<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
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- Caused by mutation in the lamin A/C gene (LMNA, <a href="/entry/150330#0022">150330.0022</a>)<br />
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<h5>
Progeria
- <a href="/phenotypicSeries/PS176670">PS176670</a>
- 4 Entries
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<a href="/geneMap/1/1240?start=-3&limit=10&highlight=1240"> 1q22 </a>
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<a href="/entry/176670"> Hutchinson-Gilford progeria </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/176670"> 176670 </a>
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<a href="/entry/150330"> LMNA </a>
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<a href="/entry/150330"> 150330 </a>
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<a href="/geneMap/7/109?start=-3&limit=10&highlight=109"> 7p15.3 </a>
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<a href="/entry/620601"> Garg-Mishra progeroid syndrome </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/620601"> 620601 </a>
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<a href="/entry/607980"> TOMM7 </a>
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<a href="/entry/607980"> 607980 </a>
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<a href="/geneMap/10/327?start=-3&limit=10&highlight=327"> 10q22.3 </a>
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<a href="/entry/264090"> Wiedemann-Rautenstrauch syndrome </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/264090"> 264090 </a>
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<a href="/entry/614258"> POLR3A </a>
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<a href="/entry/614258"> 614258 </a>
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<a href="/geneMap/11/619?start=-3&limit=10&highlight=619"> 11q13.1 </a>
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<a href="/entry/614008"> Nestor-Guillermo progeria syndrome </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/614008"> 614008 </a>
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<a href="/entry/603811"> BANF1 </a>
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<span class="mim-font">
<a href="/entry/603811"> 603811 </a>
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<p>A number sign (#) is used with this entry because both classic infantile-onset and later childhood-onset Hutchinson-Gilford progeria syndrome (HGPS) are caused by de novo heterozygous mutation in the lamin A gene (LMNA; <a href="/entry/150330">150330</a>) on chromosome 1q22.</p>
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<strong>Description</strong>
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<p>Hutchinson-Gilford progeria syndrome is a rare disorder characterized by short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early death. Cognitive development is normal. Onset is usually within the first year of life (review by <a href="#31" class="mim-tip-reference" title="Hennekam, R. C. M. &lt;strong&gt;Hutchinson-Gilford progeria syndrome: review of the phenotype.&lt;/strong&gt; Am. J. Med. Genet. 140A: 2603-2624, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16838330/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16838330&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31346&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16838330">Hennekam, 2006</a>). The designation Hutchinson-Gilford progeria syndrome appears to have been first used by <a href="#16" class="mim-tip-reference" title="DeBusk, F. L. &lt;strong&gt;The Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Pediat. 80: 697-724, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4552697/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4552697&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(72)80229-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4552697">DeBusk (1972)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4552697+16838330" 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 subset of patients with heterozygous mutations in the LMNA gene and a phenotype similar to HGPS have shown onset of the disorder in late childhood or in the early teenage years, and have longer survival than observed in classic HGPS (<a href="#11" class="mim-tip-reference" title="Chen, L., Lee, L., Kudlow, B. A., Dos Santos, H. G., Sletvold, O., Shafeghati, Y., Botha, E. G., Garg, E., Hanson, N. B., Martin, G. M., Mian, I. S., Kennedy, B. K., Oshima, J. &lt;strong&gt;LMNA mutations in atypical Werner&#x27;s syndrome.&lt;/strong&gt; Lancet 362: 440-445, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12927431/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12927431&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14069-X&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12927431">Chen et al., 2003</a>; <a href="#30" class="mim-tip-reference" title="Hegele, R. A. &lt;strong&gt;Drawing the line in progeria syndromes.&lt;/strong&gt; Lancet 362: 416-417, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12927424/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12927424&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14097-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12927424">Hegele, 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12927431+12927424" 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>Other disorders with a less severe, but overlapping phenotype include mandibuloacral dysplasia (MADA; <a href="/entry/248370">248370</a>), an autosomal disorder caused by homozygous or compound heterozygous mutations in the LMNA gene, dilated cardiomyopathy with hypergonadotropic hypogonadism (<a href="/entry/212112">212112</a>), caused by heterozygous mutation in the LMNA gene, and Werner syndrome (<a href="/entry/277700">277700</a>), an autosomal recessive progeroid syndrome caused by homozygous or compound heterozygous mutations in the RECQL2 gene (<a href="/entry/604611">604611</a>).</p>
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<p>Hastings <a href="#24" class="mim-tip-reference" title="Gilford, H. &lt;strong&gt;Ateleiosis and progeria: continuous youth and premature old age.&lt;/strong&gt; Brit. Med. J. 2: 914-918, 1904."None>Gilford (1904)</a> gave the name progeria to this disorder in an article in which he also assigned the term ateleiosis to a pituitary growth hormone deficiency (<a href="/entry/262400">262400</a>). He provided no photographs of progeria and indicated that 'only two well-marked instances have so far been recorded.' Death from angina pectoris at age 18 years was noted. Jonathan <a href="#33" class="mim-tip-reference" title="Hutchinson, J. &lt;strong&gt;Case of congenital absence of hair, with atrophic condition of the skin and its appendages, in a boy whose mother had been almost wholly bald from alopecia areata from the age of six.&lt;/strong&gt; Lancet I: 923 only, 1886."None>Hutchinson (1886)</a> had previously written about the disorder (<a href="#44" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;The clinical observations of Jonathan Hutchinson.&lt;/strong&gt; Am. J. Syph. 36: 101-126, 1952.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14903422/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14903422&lt;/a&gt;]" pmid="14903422">McKusick, 1952</a>). Hutchinson's report was accompanied by a photograph of his patient at the age of 15.5 years showing the stereotypic phenotype of this disorder. Hutchinson emphasized the lack of hair but the other features were evident: disproportionately large head, 'pinched' facial features, lipodystrophy, incomplete extension at the knees and elbows indicating stiffness of joints, and generally a senile appearance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14903422" 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="#51" class="mim-tip-reference" title="Paterson, D. &lt;strong&gt;Case of progeria.&lt;/strong&gt; Proc. Roy. Soc. Med. 16: 42 only, 1922."None>Paterson (1922)</a> recorded the cases of 2 possibly affected brothers whose parents were first cousins. Photographs were not published and the diagnosis is not completely certain. The full report was simply the following: 'A boy, aged 8 years. Condition has been present since birth... There are 4 children in the family; the girls are unaffected, both boys are affected. The senile condition of the skin and facies should be noted. The vessels show arteriosclerosis. (There is almost complete absence of subcutaneous fat.)'</p><p><a href="#49" class="mim-tip-reference" title="Ogihara, T., Hata, T., Tanaka, K., Fukuchi, K., Tabuchi, Y., Kumahara, Y. &lt;strong&gt;Hutchinson-Gilford progeria syndrome in a 45-year-old man.&lt;/strong&gt; Am. J. Med. 81: 135-138, 1986. Note: Erratum: Am. J. Med. 82: 869 only, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3728539/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3728539&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9343(86)90196-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3728539">Ogihara et al. (1986)</a> described a Japanese patient with progeria who survived to age 45, dying of myocardial infarction. Clinically, he seemed typical except for the unusually long survival. According to reviews of the literature, the age at death ranges from 7 to 27.5 years, with a median age of 13.4 years. <a href="#18" class="mim-tip-reference" title="Dyck, J. D., David, T. E., Burke, B., Webb, G. D., Henderson, M. A., Fowler, R. S. &lt;strong&gt;Management of coronary artery disease in Hutchinson-Gilford syndrome.&lt;/strong&gt; J. Pediat. 111: 407-410, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2957478/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2957478&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(87)80466-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2957478">Dyck et al. (1987)</a> reported coronary artery bypass surgery and percutaneous transluminal angioplasty in a 14-year-old girl with this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3728539+2957478" 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>The 2 brothers reported as having progeria by <a href="#50" class="mim-tip-reference" title="Parkash, H., Sidhu, S. S., Raghavan, R., Deshmukh, R. N. &lt;strong&gt;Hutchinson-Gilford progeria: familial occurrence.&lt;/strong&gt; Am. J. Med. Genet. 36: 431-433, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2389799/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2389799&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320360411&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2389799">Parkash et al. (1990)</a> probably had mandibuloacral dysplasia (MADA; <a href="/entry/248370">248370</a>). <a href="#21" class="mim-tip-reference" title="Fatunde, O. J., Benka-Coker, L. B. O., Scott-Emuakpor, A. B. &lt;strong&gt;Familial occurrence of progeria (Hutchinson-Gilford progeria syndrome). (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 47 (suppl.): A55 only, 1990."None>Fatunde et al. (1990)</a> described a family in which 3 of 6 sibs had progeria. A seventh sib, who had died before the time of study, may have been affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2389799" 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>Three cases of neonatal HGPS were reported in France (<a href="#13" class="mim-tip-reference" title="De Martinville, B., Sorin, M., Briard, M. L., Frezal, J. &lt;strong&gt;Progeria de Gilford-Hutchinson a debut neonatal chez des jumeaux monozygotes.&lt;/strong&gt; Arch. Franc. Pediat. 37: 679-681, 1980."None>De Martinville et al., 1980</a>; <a href="#37" class="mim-tip-reference" title="Labeille, B., Dupuy, P., Frey-Follezou, I., Larregue, M., Maquart, F. X., Borel, J. P., Gallet, M., Risbourg, B., Denceux, J. P. &lt;strong&gt;Progeria de Hutchinson-Gilford neonatale avec atteinte cutanee sclerodermiforme.&lt;/strong&gt; Ann. Derm. Venereol. 114: 233-242, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3579140/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3579140&lt;/a&gt;]" pmid="3579140">Labeille et al., 1987</a>). All 3 patients died early, 2 on the first day of life and the other patient at 20 months of age. Unlike classic HGPS, however, none of the 3 presented clinical signs of coronary occlusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3579140" 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="#14" class="mim-tip-reference" title="de Paula Rodrigues, G. H., das Eiras Tamega, I., Duque, G., Spinola Dias Neto, V. &lt;strong&gt;Severe bone changes in a case of Hutchinson-Gilford syndrome.&lt;/strong&gt; Ann. Genet. 45: 151-155, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12381448/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12381448&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0003-3995(02)01119-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12381448">De Paula Rodrigues et al. (2002)</a> reported details of the involvement of bones and joints in a seemingly typical example of progeria in an 8-year-old girl. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12381448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Hennekam, R. C. M. &lt;strong&gt;Hutchinson-Gilford progeria syndrome: review of the phenotype.&lt;/strong&gt; Am. J. Med. Genet. 140A: 2603-2624, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16838330/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16838330&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31346&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16838330">Hennekam (2006)</a> provided an exhaustive review of the phenotype of HGPS, based on data from 10 of his own cases and 132 cases from the literature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16838330" 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="#46" class="mim-tip-reference" title="Merideth, M. A., Gordon, L. B., Clauss, S., Sachdev, V., Smith, A. C. M., Perry, M. B., Brewer, C. C., Zalewski, C., Kim, H. J., and 13 others. &lt;strong&gt;Phenotype and course of Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; New Eng. J. Med. 358: 592-604, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18256394/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18256394&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=18256394[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa0706898&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18256394">Merideth et al. (2008)</a> comprehensively studied 15 children between 1 and 17 years of age, representing nearly half of the world's known patients with Hutchinson-Gilford progeria syndrome. The previously described features were documented. Previously unrecognized findings included prolonged prothrombin times, elevated platelet counts and serum phosphorus levels, low-frequency conductive hearing loss, and functional oral deficits. Growth impairment was not related to inadequate nutrition, insulin unresponsiveness, or growth hormone deficiency. Growth hormone treatment in a few patients increased height growth by 10% and weight growth by 50%. Cardiovascular studies revealed diminishing vascular function with age, including elevated blood pressure, reduced vascular compliance, decreased ankle-brachial indices, and adventitial thickening. The ankle-brachial index was used to measure the difference in blood pressure between the legs and arms in 11 children. The index was abnormal in 2 patients, indicating arterial disease in the legs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18256394" 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>Childhood-Onset HGPS</em></strong></p><p>
<a href="#11" class="mim-tip-reference" title="Chen, L., Lee, L., Kudlow, B. A., Dos Santos, H. G., Sletvold, O., Shafeghati, Y., Botha, E. G., Garg, E., Hanson, N. B., Martin, G. M., Mian, I. S., Kennedy, B. K., Oshima, J. &lt;strong&gt;LMNA mutations in atypical Werner&#x27;s syndrome.&lt;/strong&gt; Lancet 362: 440-445, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12927431/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12927431&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14069-X&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12927431">Chen et al. (2003)</a> found that 26 (20%) of 129 probands referred to their international registry for molecular diagnosis of the autosomal recessive progeroid disorder Werner syndrome (<a href="/entry/277700">277700</a>) did not have mutations in the RECQL2 gene (<a href="/entry/604611">604611</a>). Sequencing of the LMNA gene in these individuals found that 4 (15%) had heterozygous mutations: A57P (<a href="/entry/150330#0030">150330.0030</a>), R133L (in 2 persons) (<a href="/entry/150330#0027">150330.0027</a>), and L140R (<a href="/entry/150330#0031">150330.0031</a>), all of which altered relatively conserved residues within lamin A/C. Fibroblasts from the patient with the L140R mutation had a substantially enhanced proportion of nuclei with altered morphology and mislocalized lamins. These individuals had a more severe phenotype than those with RECQL2-associated Werner syndrome. Although <a href="#11" class="mim-tip-reference" title="Chen, L., Lee, L., Kudlow, B. A., Dos Santos, H. G., Sletvold, O., Shafeghati, Y., Botha, E. G., Garg, E., Hanson, N. B., Martin, G. M., Mian, I. S., Kennedy, B. K., Oshima, J. &lt;strong&gt;LMNA mutations in atypical Werner&#x27;s syndrome.&lt;/strong&gt; Lancet 362: 440-445, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12927431/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12927431&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14069-X&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12927431">Chen et al. (2003)</a> designated these patients as having 'atypical Werner syndrome,' <a href="#30" class="mim-tip-reference" title="Hegele, R. A. &lt;strong&gt;Drawing the line in progeria syndromes.&lt;/strong&gt; Lancet 362: 416-417, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12927424/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12927424&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14097-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12927424">Hegele (2003)</a> suggested that the patients more likely had late-onset Hutchinson-Gilford progeria syndrome. <a href="#30" class="mim-tip-reference" title="Hegele, R. A. &lt;strong&gt;Drawing the line in progeria syndromes.&lt;/strong&gt; Lancet 362: 416-417, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12927424/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12927424&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14097-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12927424">Hegele (2003)</a> reviewed the clinical features of the 4 patients with LMNA mutations reported by <a href="#11" class="mim-tip-reference" title="Chen, L., Lee, L., Kudlow, B. A., Dos Santos, H. G., Sletvold, O., Shafeghati, Y., Botha, E. G., Garg, E., Hanson, N. B., Martin, G. M., Mian, I. S., Kennedy, B. K., Oshima, J. &lt;strong&gt;LMNA mutations in atypical Werner&#x27;s syndrome.&lt;/strong&gt; Lancet 362: 440-445, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12927431/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12927431&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14069-X&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12927431">Chen et al. (2003)</a>, and stated that the designation of 'atypical Werner syndrome' appeared somewhat insecure. He noted that the comparatively young ages of onset in the patients with mutant LMNA would be just as consistent with late-onset HGPS as with early-onset Werner syndrome. These patients also expressed features of nonprogeroid laminopathies, including insulin resistance (FPLD2; <a href="/entry/151660">151660</a>), dilated cardiomyopathy (<a href="/entry/115200">115200</a>), and phalangeal osteosclerosis (MADA; <a href="/entry/248370">248370</a>). <a href="#30" class="mim-tip-reference" title="Hegele, R. A. &lt;strong&gt;Drawing the line in progeria syndromes.&lt;/strong&gt; Lancet 362: 416-417, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12927424/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12927424&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14097-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12927424">Hegele (2003)</a> suggested that genomic DNA analysis can help draw a diagnostic line that clarifies potential overlap between older patients with Hutchinson-Gilford syndrome and younger patients with Werner syndrome, and that therapies may depend on precise molecular classification. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12927431+12927424" 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="#45" class="mim-tip-reference" title="McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F. &lt;strong&gt;Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.&lt;/strong&gt; Am. J. Med. Genet. 149A: 567-572, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19283854/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19283854&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32627&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19283854">McPherson et al. (2009)</a> noted phenotypic similarities between the patient studied by <a href="#11" class="mim-tip-reference" title="Chen, L., Lee, L., Kudlow, B. A., Dos Santos, H. G., Sletvold, O., Shafeghati, Y., Botha, E. G., Garg, E., Hanson, N. B., Martin, G. M., Mian, I. S., Kennedy, B. K., Oshima, J. &lt;strong&gt;LMNA mutations in atypical Werner&#x27;s syndrome.&lt;/strong&gt; Lancet 362: 440-445, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12927431/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12927431&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/S0140-6736(03)14069-X&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12927431">Chen et al. (2003)</a> with the A57P LMNA mutation and 2 unrelated patients with heterozygosity for an adjacent mutation in the LMNA gene, L59R (<a href="/entry/150330#0052">150330.0052</a>). Features common to these 3 patients included premature ovarian failure, dilated cardiomyopathy, lipodystrophy, and progressive facial and skeletal changes involving micrognathia and sloping shoulders, but not acroosteolysis. Although the appearance of these patients was somewhat progeroid, none had severe growth failure, alopecia, or rapidly progressive atherosclerosis, and <a href="#45" class="mim-tip-reference" title="McPherson, E., Turner, L., Zador, I., Reynolds, K., Macgregor, D., Giampietro, P. F. &lt;strong&gt;Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.&lt;/strong&gt; Am. J. Med. Genet. 149A: 567-572, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19283854/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19283854&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32627&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19283854">McPherson et al. (2009)</a> suggested that the phenotype represents a distinct laminopathy (dilated cardiomyopathy and hypergonadotropic hypogonadism, <a href="/entry/212112">212112</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19283854+12927431" 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="#32" class="mim-tip-reference" title="Hisama, F. M., Lessel, D., Leistritz, D., Friedrich, K., McBride, K. L., Pastore, M. T., Gottesman, G. S., Saha, B., Martin, G. M., Kubisch, C., Oshima, J. &lt;strong&gt;Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.&lt;/strong&gt; Am. J. Med. Genet. 155A: 3002-3006, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22065502/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22065502&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22065502[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34336&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22065502">Hisama et al. (2011)</a> reported a nonconsanguineous family in which 2 sibs and their mother had adult-onset coronary artery disease with progeroid features. The patients had short stature and a progeroid appearance as adults, including loss of subcutaneous fat, hair loss, tooth loss, low bone density, and beaked nose. Cardiac features included hyperlipidemia and hypercholesterolemia resulting in severe atherosclerosis necessitating bypass surgery in 2 patients. Two patients also developed diabetes. None of the patients had cataracts. A 48-year-old woman from an unrelated family had a similar phenotype, with short stature, progeroid appearance, tight and atrophic skin, and hyperlipidemia with coronary artery disease. She died of surgical complications after bypass surgery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22065502" 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="#35" class="mim-tip-reference" title="Kane, M. S., Lindsay, M. E., Judge, D. P., Barrowman, J., Ap Rhys, C., Simonson, L., Dietz, H. C., Michaelis, S. &lt;strong&gt;LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.&lt;/strong&gt; Am. J. Med. Genet. 161A: 1599-1611, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23666920/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23666920&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23666920[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.35971&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23666920">Kane et al. (2013)</a> reported a family in which 5 individuals had a progeroid syndrome with prominent cutaneous and cardiovascular manifestations. The proband and her sister were described in detail. Both were normal at birth, but lost eyebrows and eyelashes in childhood. In their late twenties, both showed a progeroid appearance and developed exertional dyspnea associated with mitral valve calcification and stenosis necessitating valve replacement; the proband also had aortic stenosis. The proband developed occlusion of the coronary arteries and died of acute myocardial infarction at age 44; her sister died of intracranial hemorrhage at age 34. Both women also had several primary malignancies, including basal and squamous cell carcinomas, papillary renal carcinoma, and carcinoid tumor. Family history revealed a father, paternal uncle, and paternal grandfather with premature aging and significant cardiac disease resulting in death between ages 29 and 44 years. <a href="#35" class="mim-tip-reference" title="Kane, M. S., Lindsay, M. E., Judge, D. P., Barrowman, J., Ap Rhys, C., Simonson, L., Dietz, H. C., Michaelis, S. &lt;strong&gt;LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.&lt;/strong&gt; Am. J. Med. Genet. 161A: 1599-1611, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23666920/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23666920&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23666920[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.35971&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23666920">Kane et al. (2013)</a> proposed the name LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23666920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Barthelemy, F., Navarro, C., Fayek, R., Da Silva, N., Roll, P., Sigaudy, S., Oshima, J., Bonne, G., Papadopoulou-Legbelou, K., Evangeliou, A. E., Spilioti, M., Lemerrer, M., Wevers, R. A., Morava, E., Robaglia-Schlupp, A., Levy, N., Bartoli, M., De Sandre-Giovannoli, A. &lt;strong&gt;Truncated prelamin A expression in HGPS-like patients: a transcriptional study.&lt;/strong&gt; Europ. J. Hum. Genet. 23: 1051-1061, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25649378/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25649378&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25649378[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2014.239&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25649378">Barthelemy et al. (2015)</a> reported a patient with late-onset HGPS. He was first seen at age 30 years, when he showed a progeroid appearance with facial dysmorphism, lipoatrophy, thin skin, hair loss, and brittle nails. He had hypertriglyceridemia, osteolysis of the distal phalanges, and diffuse and severe atherosclerosis and aortic stenosis necessitating cardiac surgery. He died of surgical complications at age 35. An unrelated patient presented at age 12 years with short stature and a progeroid appearance, including atrophic skin, alopecia, amyotrophy, lipoatrophy, and distal phalangeal osteolysis. He developed aortic valve stenosis and hypertrophic cardiomyopathy resulting in death at age 17. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25649378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
<a id="biochemicalFeatures" class="mim-anchor"></a>
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
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<strong>Biochemical Features</strong>
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<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
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<p>In cultured skin fibroblasts of patients with progeria, <a href="#28" class="mim-tip-reference" title="Goldstein, S., Moerman, E. J. &lt;strong&gt;Heat-labile enzymes in circulating erythrocytes of a progeria family.&lt;/strong&gt; Am. J. Hum. Genet. 30: 167-173, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/655163/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;655163&lt;/a&gt;]" pmid="655163">Goldstein and Moerman (1978)</a> demonstrated an increased fraction of heat-labile enzymes and other altered proteins. Freshly obtained cells, namely, erythrocytes, showed similar heat-lability of G6PD and 6-phosphogluconate dehydrogenases in a girl with progeria. Both parents showed intermediate values, consistent with recessive inheritance. Normal HLA antigens were found by <a href="#5" class="mim-tip-reference" title="Brown, W. T., Darlington, G. J., Arnold, A., Fotino, M. &lt;strong&gt;Detection of HLA antigens on progeria syndrome fibroblasts.&lt;/strong&gt; Clin. Genet. 17: 213-219, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6988117/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6988117&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1980.tb00135.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6988117">Brown et al. (1980)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=655163+6988117" 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="Cao, K., Graziotto, J. J., Blair, C. D., Mazzulli, J. R., Erdos, M. R., Krainc, D., Collins, F. S. &lt;strong&gt;Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.&lt;/strong&gt; Sci. Transl. Med. 3: 89ra58, 2011. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21715679/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21715679&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/scitranslmed.3002346&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21715679">Cao et al. (2011)</a> reported the effect of rapamycin on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the formation of insoluble progerin aggregates and induced clearance through autophagic mechanisms in normal fibroblasts. <a href="#10" class="mim-tip-reference" title="Cao, K., Graziotto, J. J., Blair, C. D., Mazzulli, J. R., Erdos, M. R., Krainc, D., Collins, F. S. &lt;strong&gt;Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.&lt;/strong&gt; Sci. Transl. Med. 3: 89ra58, 2011. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21715679/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21715679&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/scitranslmed.3002346&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21715679">Cao et al. (2011)</a> concluded that their findings suggested an additional mechanism for the beneficial effects of rapamycin on longevity and encouraged the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21715679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Larrieu, D., Britton, S., Demir, M., Rodriguez, R., Jackson, S. P. &lt;strong&gt;Chemical inhibition of NAT10 corrects defects of laminopathic cells.&lt;/strong&gt; Science 344: 527-532, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24786082/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24786082&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24786082[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.1252651&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24786082">Larrieu et al. (2014)</a> identified a small molecule that they called 'remodelin' that improved nuclear architecture, chromatin organization, and fitness of both human LMNA (<a href="/entry/150330">150330</a>)-depleted cells and HGPS-derived patient cells, and decreased markers of DNA damage in these cells. Using a combination of chemical, cellular, and genetic approaches, <a href="#38" class="mim-tip-reference" title="Larrieu, D., Britton, S., Demir, M., Rodriguez, R., Jackson, S. P. &lt;strong&gt;Chemical inhibition of NAT10 corrects defects of laminopathic cells.&lt;/strong&gt; Science 344: 527-532, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24786082/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24786082&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24786082[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.1252651&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24786082">Larrieu et al. (2014)</a> identified NAT10 (<a href="/entry/609221">609221</a>) as the target of remodelin that mediated nuclear shape rescue in laminopathic cells via microtubule reorganization. <a href="#38" class="mim-tip-reference" title="Larrieu, D., Britton, S., Demir, M., Rodriguez, R., Jackson, S. P. &lt;strong&gt;Chemical inhibition of NAT10 corrects defects of laminopathic cells.&lt;/strong&gt; Science 344: 527-532, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24786082/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24786082&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24786082[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.1252651&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24786082">Larrieu et al. (2014)</a> concluded that these findings provided insights into how NAT10 affects nuclear architecture and suggested alternative strategies for treating laminopathies and aging. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24786082" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div>
<a id="inheritance" class="mim-anchor"></a>
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Inheritance</strong>
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</h4>
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<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>The majority of patients with HGPS have de novo heterozygous dominant mutations in the LMNA gene. Presumably, patients with the disorder do not survive long enough to reproduce (<a href="#20" class="mim-tip-reference" title="Eriksson, M., Brown, W. T., Gordon, L. B., Glynn, M. W., Singer, J., Scott, L., Erdos, M. R., Robbins, C. M., Moses, T. Y., Berglund, P., Dutra, A., Pak, E., Durkin, S., Csoka, A. B., Boehnke, M., Glover, T. W., Collins, F. S. &lt;strong&gt;Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Nature 423: 293-298, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12714972/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12714972&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature01629&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12714972">Eriksson et al., 2003</a>; <a href="#9" class="mim-tip-reference" title="Cao, H., Hegele, R. A. &lt;strong&gt;LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).&lt;/strong&gt; J. Hum. Genet. 48: 271-274, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12768443/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12768443&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10038-003-0025-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12768443">Cao and Hegele, 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12714972+12768443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="DeBusk, F. L. &lt;strong&gt;The Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Pediat. 80: 697-724, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4552697/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4552697&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(72)80229-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4552697">DeBusk (1972)</a> maintained that of 19 cases reported to that date in which consanguinity was sought, in only 3 were the parents related. He suggested that progeria could conceivably be dominant and the rare instances of affected sibs be the result of germinal mosaicism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4552697" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="DeBusk, F. L. &lt;strong&gt;The Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Pediat. 80: 697-724, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4552697/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4552697&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(72)80229-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4552697">DeBusk (1972)</a> and <a href="#34" class="mim-tip-reference" title="Jones, K. L., Smith, D. W., Harvey, M. A. S., Hall, B. D., Quan, L. &lt;strong&gt;Older paternal age and fresh gene mutation: data on additional disorders.&lt;/strong&gt; J. Pediat. 86: 84-88, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1110452/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1110452&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(75)80709-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1110452">Jones et al. (1975)</a> reported a paternal age effect, supporting autosomal dominant inheritance. In 20 cases in which parental age was known, the mean paternal and maternal ages were 35.6 and 28.8 years, respectively, and the median ages 31 and 28, respectively. In 7 U.S. cases, the mean paternal age was 37.1. On the basis of the paternal age effect, the low frequency of parental consanguinity, and the report of progeric monozygotic twins of 14 normal sibs, <a href="#7" class="mim-tip-reference" title="Brown, W. T. &lt;strong&gt;Human mutations affecting aging--a review.&lt;/strong&gt; Mech. Aging Dev. 9: 325-336, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/155763/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;155763&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0047-6374(79)90109-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="155763">Brown (1979)</a> favored autosomal dominant inheritance, with most cases resulting from a de novo, new, mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1110452+4552697+155763" 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 Hutchinson-Gilford progeria, <a href="#61" class="mim-tip-reference" title="Wuyts, W., Biervliet, M., Reyniers, E., D&#x27;Apice, M. R., Novelli, G., Storm, K. &lt;strong&gt;Somatic and gonadal mosaicism in Hutchinson-Gilford progeria.&lt;/strong&gt; Am. J. Med. Genet. 135A: 66-68, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15793835/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15793835&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30663&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15793835">Wuyts et al. (2005)</a> identified a heterozygous mutation in the LMNA gene (G608G; <a href="/entry/150330#0022">150330.0022</a>). In lymphocyte DNA from the parents, normal wildtype alleles were observed in the father, but a low signal corresponding to the mutant allele was detected in the mother's DNA. A segregation study confirmed that the patient's mutation was transmitted from the mother, who showed germline and somatic mosaicism without clinical manifestations of HGPS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15793835" 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>Reports Suggesting Autosomal Recessive Inheritance</em></strong></p><p>
Recessive inheritance was suggested by the report from Egypt of affected sisters, children of first cousins (<a href="#23" class="mim-tip-reference" title="Gabr, M., Hashem, N., Hashem, M., Fahmi, A., Safouh, M. &lt;strong&gt;Progeria, a pathologic study.&lt;/strong&gt; J. Pediat. 57: 70-77, 1960.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13825821/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;13825821&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(60)80213-2&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="13825821">Gabr et al., 1960</a>). <a href="#19" class="mim-tip-reference" title="Erecinski, K., Bittel-Dobrzynska, N., Mostowiec, S. &lt;strong&gt;Zespol progerii u dwoch braci.&lt;/strong&gt; Pol. Tyg. Lek. 16: 806-809, 1961.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13697090/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;13697090&lt;/a&gt;]" pmid="13697090">Erecinski et al. (1961)</a> described photographically typical progeria in 2 brothers. Among the 9 offspring of 2 sisters, <a href="#54" class="mim-tip-reference" title="Rava, G. &lt;strong&gt;Su un nucleo familiare di progeria.&lt;/strong&gt; Minerva Med. 58: 1502-1509, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6026632/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6026632&lt;/a&gt;]" pmid="6026632">Rava (1967)</a> found 6 affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13697090+13825821+6026632" 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="#41" class="mim-tip-reference" title="Maciel, A. T. &lt;strong&gt;Evidence for autosomal recessive inheritance of progeria (Hutchinson Gilford).&lt;/strong&gt; Am. J. Med. Genet. 31: 483-487, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3228132/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3228132&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320310302&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3228132">Maciel (1988)</a> reported an inbred Brazilian family in which presumed Hutchinson-Gilford progeria syndrome had occurred in members of 2 sibships related as first cousins once removed. Although autosomal recessive inheritance was unmistakable, the disorder was not definitively HGPS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3228132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Khalifa, M. M. &lt;strong&gt;Hutchinson-Gilford progeria syndrome: report of a Libyan family and evidence of autosomal recessive inheritance.&lt;/strong&gt; Clin. Genet. 35: 125-132, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2721021/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2721021&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1989.tb02917.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2721021">Khalifa (1989)</a> described a consanguineous Libyan family in which 2 males and 1 female in 2 sibships related as cousins had seemingly typical Hutchinson-Gilford progeria. Repeated nonhealing fractures were the presenting manifestation in the proband. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2721021" 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="#58" class="mim-tip-reference" title="Verstraeten, V. L. R. M., Broers, J. L. V., van Steensel, M. A. M., Zinn-Justin, S., Ramaekers, F. C. S., Steijlen, P. M., Kamps, M., Kuijpers, H. J. H., Merckx, D., Smeets, H. J. M., Hennekam, R. C. M., Marcelis, C. L. M., van den Wijngaard, A. &lt;strong&gt;Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation.&lt;/strong&gt; Hum. Molec. Genet. 15: 2509-2522, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16825282/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16825282&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddl172&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16825282">Verstraeten et al. (2006)</a> reported a 2-year-old Dutch boy with features of HGPS who was compound heterozygous for 2 mutations in the LMNA gene. After the age of 1 year, he showed failure to thrive, poor growth, and hair loss. Clinical features included prominent forehead, prominent veins, narrow nasal bridge, small mouth, lipodystrophy, and dental crowding. He also had significant shortening of the distal phalanges with osteolysis and tufting, as well as osteoresorption of the distal ends of the clavicles. Some of these features were more consistent with mandibuloacral dysplasia. Fibroblasts derived from the patient showed irregularly shaped nuclei with blebs, honeycomb figures, large and poorly defined protrusions, and intra/trans-nuclear tubule-like structures. There was no accumulation of prelamin A, as usually observed in typical HGPS. A clinically unaffected sister was heterozygous for 1 of the mutations, and each clinically unaffected parent was heterozygous for 1 of the mutations. A smaller percentage of fibroblasts derived from the parents showed the nuclear abnormalities that were present in the proband. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16825282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Brown, W. T., Abdenur, J., Goonewardena, P., Alemzadeh, R., Smith, M., Friedman, S., Cervantes, C., Bandyopadhyay, S., Zaslav, A., Kunaporn, S., Serotkin, A., Lifshitz, F. &lt;strong&gt;Hutchinson-Gilford progeria syndrome: clinical, chromosomal and metabolic abnormalities. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 47 (suppl.): A50 only, 1990."None>Brown et al. (1990)</a> described identical twins with progeria who developed heart failure at the age of 8 and died within 1 month of each other. Cytogenetic analysis showed an inverted insertion in the long arm of chromosome 1 in 70% of cells. <a href="#4" class="mim-tip-reference" title="Brown, W. T., Abdenur, J., Goonewardena, P., Alemzadeh, R., Smith, M., Friedman, S., Cervantes, C., Bandyopadhyay, S., Zaslav, A., Kunaporn, S., Serotkin, A., Lifshitz, F. &lt;strong&gt;Hutchinson-Gilford progeria syndrome: clinical, chromosomal and metabolic abnormalities. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 47 (suppl.): A50 only, 1990."None>Brown et al. (1990)</a> suggested that a gene for progeria may be located on chromosome 1. Evidence for possible bioinactive growth hormone was presented with a suggestion of treatment of progeria with growth hormone.</p><p>In a 9-year-old patient with a classic clinical picture of Hutchinson-Gilford progeria, <a href="#17" class="mim-tip-reference" title="Delgado Luengo, W.., Rojas Martinez, A., Ortiz Lopez, R., Martinez Basalo, C., Rojas-Atencio, A., Quintero, M., Borjas, L., Morales-Machin, A., Gonzalez Ferrer, S., Pineda Bernal, L., Canizalez-Tarazona, J., Pena, J., Delgado Luengo, J., Chacin Hernandez, J., Chang, J. C. &lt;strong&gt;Del(1)(q23) in a patient with Hutchinson-Gilford progeria.&lt;/strong&gt; Am. J. Med. Genet. 113: 298-301, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12439901/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12439901&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.10753&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12439901">Delgado Luengo et al. (2002)</a> found an interstitial deletion of chromosome 1q23. Because a perturbation in glycosylation in connective tissue had been demonstrated in patients with this condition, they suggested that the defect may reside in the B4GALT3 gene (<a href="/entry/604014">604014</a>), which maps to 1q23. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12439901" 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="#39" class="mim-tip-reference" title="Lewis, M. &lt;strong&gt;PRELP, collagen, and a theory of Hutchinson-Gilford progeria.&lt;/strong&gt; Ageing Res. Rev. 2: 95-105, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12437997/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12437997&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s1568-1637(02)00044-2&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12437997">Lewis (2003)</a> suggested that the defect causing progeria might reside in the proline/arginine-rich end leucine-rich repeat protein gene (PRELP; <a href="/entry/601914">601914</a>), which maps to chromosome 1q32 and is a small leucine-rich proteoglycan that binds type I collagen to basement membranes and type II collagen to cartilage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12437997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#31" class="mim-tip-reference" title="Hennekam, R. C. M. &lt;strong&gt;Hutchinson-Gilford progeria syndrome: review of the phenotype.&lt;/strong&gt; Am. J. Med. Genet. 140A: 2603-2624, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16838330/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16838330&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31346&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16838330">Hennekam (2006)</a> stated that the incidence of HGPS was 1 per 8 million newborns in the US between 1915 and 1967 and 1 per 4 million newborns in the Netherlands between 1900 and 2005. Patients have been reported from all continents and all ethnic backgrounds. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16838330" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#20" class="mim-tip-reference" title="Eriksson, M., Brown, W. T., Gordon, L. B., Glynn, M. W., Singer, J., Scott, L., Erdos, M. R., Robbins, C. M., Moses, T. Y., Berglund, P., Dutra, A., Pak, E., Durkin, S., Csoka, A. B., Boehnke, M., Glover, T. W., Collins, F. S. &lt;strong&gt;Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Nature 423: 293-298, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12714972/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12714972&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature01629&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12714972">Eriksson et al. (2003)</a> reported de novo point mutations in lamin A (<a href="/entry/150330">150330</a>) causing Hutchinson-Gilford progeria syndrome. The HGPS gene was initially localized to chromosome 1q by observing 2 cases of uniparental isodisomy of 1q, and 1 case with a 6-Mb paternal interstitial deletion. Eighteen of 20 classic cases of HGPS harbored the identical de novo single-base substitution, a C-to-T transition resulting in a silent gly-to-gly change at codon 608 within exon 11 (G608G; <a href="/entry/150330#0022">150330.0022</a>). One additional case was identified with a different substitution within the same codon (<a href="/entry/150330#0023">150330.0023</a>). Both of these mutations were shown to result in activation of a cryptic splice site within exon 11 of the lamin A gene, resulting in production of a protein product that deletes 50 amino acids near the C terminus. This prelamin A still retains the CAAX box but lacks the site for endoproteolytic cleavage. Immunofluorescence of HGPS fibroblasts with antibodies directed against lamin A revealed that many cells showed visible abnormalities of the nuclear membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12714972" 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="Cao, H., Hegele, R. A. &lt;strong&gt;LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).&lt;/strong&gt; J. Hum. Genet. 48: 271-274, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12768443/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12768443&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10038-003-0025-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12768443">Cao and Hegele (2003)</a> studied cell lines from 7 HGPS probands. Five carried the common mutation within exon 11 of LMNA, which they termed 2036C-T (<a href="/entry/150330#0022">150330.0022</a>). In 1 of 7 patients, they identified the G608S mutation (<a href="/entry/150330#0023">150330.0023</a>). <a href="#9" class="mim-tip-reference" title="Cao, H., Hegele, R. A. &lt;strong&gt;LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).&lt;/strong&gt; J. Hum. Genet. 48: 271-274, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12768443/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12768443&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10038-003-0025-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12768443">Cao and Hegele (2003)</a> confirmed the findings of <a href="#20" class="mim-tip-reference" title="Eriksson, M., Brown, W. T., Gordon, L. B., Glynn, M. W., Singer, J., Scott, L., Erdos, M. R., Robbins, C. M., Moses, T. Y., Berglund, P., Dutra, A., Pak, E., Durkin, S., Csoka, A. B., Boehnke, M., Glover, T. W., Collins, F. S. &lt;strong&gt;Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Nature 423: 293-298, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12714972/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12714972&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature01629&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12714972">Eriksson et al. (2003)</a> using the same cell lines. In 1 patient with an HGPS phenotype who was 28 years old at the time that DNA was obtained, <a href="#9" class="mim-tip-reference" title="Cao, H., Hegele, R. A. &lt;strong&gt;LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).&lt;/strong&gt; J. Hum. Genet. 48: 271-274, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12768443/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12768443&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10038-003-0025-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12768443">Cao and Hegele (2003)</a> identified compound heterozygosity for 2 missense mutations in the LMNA gene (<a href="/entry/150330#0025">150330.0025</a> and <a href="/entry/150330#0026">150330.0026</a>); this patient was later determined (<a href="#8" class="mim-tip-reference" title="Brown, W. T. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Staten Island, N.Y. 1/12/2004."None>Brown, 2004</a>) to have mandibuloacral dysplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12714972+12768443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="De Sandre-Giovannoli, A., Bernard, R., Cau, P., Navarro, C., Amiel, J., Boccaccio, I., Lyonnet, S., Stewart, C. L., Munnich, A., Le Merrer, M., Levy, N. &lt;strong&gt;Lamin A truncation in Hutchinson-Gilford progeria.&lt;/strong&gt; Science 300: 2055 only, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12702809/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12702809&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.1084125&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12702809">De Sandre-Giovannoli et al. (2003)</a> identified the exon 11 cryptic splice site activation mutation (1824C-T+1819-1968del; <a href="/entry/150330#0022">150330.0022</a>) in 2 HGPS patients. Immunocytochemical analyses of lymphocytes from 1 patient using specific antibodies directed against lamin A/C, lamin A, and lamin B1 showed that most cells had strikingly altered nuclear sizes and shapes, with envelope interruptions accompanied by chromatin extrusion. Lamin A was detected in 10 to 20% of HGPS lymphocytes. Only lamin C was present in most cells, and lamin B1 was found in the nucleoplasm, suggesting that it had dissociated from the nuclear envelope due to the loss of lamin A. Western blot analysis showed 25% of normal lamin A levels, and no truncated form was detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12702809" 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 4 affected members of a consanguineous family from north India, <a href="#52" class="mim-tip-reference" title="Plasilova, M., Chattopadhyay, C., Pal, P., Schaub, N. A., Buechner, S. A., Mueller, H., Miny, P., Ghosh, A., Heinimann, K. &lt;strong&gt;Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Med. Genet. 41: 609-614, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15286156/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15286156&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2004.019661&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15286156">Plasilova et al. (2004)</a> with features of both MADA (<a href="/entry/248370">248370</a>) and HGPS resulting from a homozygous missense mutation in the LMNA gene (<a href="/entry/150330#0033">150330.0033</a>). <a href="#52" class="mim-tip-reference" title="Plasilova, M., Chattopadhyay, C., Pal, P., Schaub, N. A., Buechner, S. A., Mueller, H., Miny, P., Ghosh, A., Heinimann, K. &lt;strong&gt;Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Med. Genet. 41: 609-614, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15286156/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15286156&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2004.019661&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15286156">Plasilova et al. (2004)</a> suggested that autosomal recessive HGPS and MADA may represent a single disorder with varying degrees of severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15286156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#47" class="mim-tip-reference" title="Moulson, C. L., Fong, L. G., Gardner, J. M., Farber, E. A., Go, G., Passariello, A., Grange, D. K., Young, S. G., Miner, J. H. &lt;strong&gt;Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.&lt;/strong&gt; Hum. Mutat. 28: 882-889, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17469202/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17469202&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.20536&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17469202">Moulson et al. (2007)</a> reported 2 unrelated patients with extremely severe forms of HGPS associated with unusual mutations in the LMNA gene. (<a href="/entry/150330#0036">150330.0036</a> and <a href="/entry/150330#0040">150330.0040</a>, respectively). Both mutations resulted in increased use of the cryptic exon 11 donor splice site observed with the common 1824C-T mutation (<a href="/entry/150330#0022">150330.0022</a>). As a consequence, the ratios of mutant progerin mRNA and protein to wildtype were higher than in typical HGPS patients. The findings indicated that the level of progerin expression correlates to the severity of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17469202" 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 affected members of a family with adult-onset coronary disease and progeroid features, <a href="#32" class="mim-tip-reference" title="Hisama, F. M., Lessel, D., Leistritz, D., Friedrich, K., McBride, K. L., Pastore, M. T., Gottesman, G. S., Saha, B., Martin, G. M., Kubisch, C., Oshima, J. &lt;strong&gt;Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A.&lt;/strong&gt; Am. J. Med. Genet. 155A: 3002-3006, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22065502/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22065502&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22065502[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34336&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22065502">Hisama et al. (2011)</a> identified a heterozygous splice site mutation affecting exon 11 in the LMNA gene (c.1968G-A; <a href="/entry/150330#0055">150330.0055</a>). An unrelated patient with a similar disorder carried a different splice site mutation that also affected exon 11 (c.1968+5G-A; <a href="/entry/150330#0056">150330.0056</a>). Patient cells in both cases showed the presence of progerin at lower levels than observed in typical HGPS cells. The report illustrated the evolving genotype/phenotype relationship between the amount of progerin produced and the age of onset of the spectrum of clinical features associated with LMNA-associated progeroid syndromes. In 2 unrelated patients with late-onset HGPS and cardiac disease, <a href="#3" class="mim-tip-reference" title="Barthelemy, F., Navarro, C., Fayek, R., Da Silva, N., Roll, P., Sigaudy, S., Oshima, J., Bonne, G., Papadopoulou-Legbelou, K., Evangeliou, A. E., Spilioti, M., Lemerrer, M., Wevers, R. A., Morava, E., Robaglia-Schlupp, A., Levy, N., Bartoli, M., De Sandre-Giovannoli, A. &lt;strong&gt;Truncated prelamin A expression in HGPS-like patients: a transcriptional study.&lt;/strong&gt; Europ. J. Hum. Genet. 23: 1051-1061, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25649378/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25649378&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25649378[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2014.239&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25649378">Barthelemy et al. (2015)</a> identified different heterozygous exon 11 splice site mutations in the LMNA gene (<a href="/entry/150330#0055">150330.0055</a> and <a href="/entry/150330#0056">150330.0056</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25649378+22065502" 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 affected members of a family with a protracted form of HGPS manifest as premature cutaneous and cardiac aging, <a href="#35" class="mim-tip-reference" title="Kane, M. S., Lindsay, M. E., Judge, D. P., Barrowman, J., Ap Rhys, C., Simonson, L., Dietz, H. C., Michaelis, S. &lt;strong&gt;LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.&lt;/strong&gt; Am. J. Med. Genet. 161A: 1599-1611, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23666920/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23666920&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23666920[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.35971&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23666920">Kane et al. (2013)</a> identified a heterozygous missense mutation in the LMNA gene (D300G; <a href="/entry/150330#0057">150330.0057</a>). Skin fibroblasts derived from the proband showed abnormal morphology, including blebs, lobulation, and ringed or donut-shaped nuclei. Although the processing of lamin A and C were normal in patient cells, treatment with farnesyltransferase inhibitors resulted in improved nuclear morphology. Overexpression of the mutation in control fibroblasts led to abnormal nuclear morphology in a dominant-negative manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23666920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Barthelemy, F., Navarro, C., Fayek, R., Da Silva, N., Roll, P., Sigaudy, S., Oshima, J., Bonne, G., Papadopoulou-Legbelou, K., Evangeliou, A. E., Spilioti, M., Lemerrer, M., Wevers, R. A., Morava, E., Robaglia-Schlupp, A., Levy, N., Bartoli, M., De Sandre-Giovannoli, A. &lt;strong&gt;Truncated prelamin A expression in HGPS-like patients: a transcriptional study.&lt;/strong&gt; Europ. J. Hum. Genet. 23: 1051-1061, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25649378/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25649378&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25649378[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2014.239&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25649378">Barthelemy et al. (2015)</a> analyzed LMNA exon 11 transcripts in cells derived from patients with atypical progeroid syndromes associated with heterozygous mutations affecting the splicing of exon 11 of the LMNA gene (<a href="/entry/150330#0055">150330.0055</a> and <a href="/entry/150330#0056">150330.0056</a>). All cells carried a normal full-length prelamin A transcript, a band corresponding to prelamin A(del50) (progerin), and an additional transcript correlating to prelamin A(del90) resulting from the skipping of all of exon 11. <a href="#3" class="mim-tip-reference" title="Barthelemy, F., Navarro, C., Fayek, R., Da Silva, N., Roll, P., Sigaudy, S., Oshima, J., Bonne, G., Papadopoulou-Legbelou, K., Evangeliou, A. E., Spilioti, M., Lemerrer, M., Wevers, R. A., Morava, E., Robaglia-Schlupp, A., Levy, N., Bartoli, M., De Sandre-Giovannoli, A. &lt;strong&gt;Truncated prelamin A expression in HGPS-like patients: a transcriptional study.&lt;/strong&gt; Europ. J. Hum. Genet. 23: 1051-1061, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25649378/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25649378&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25649378[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2014.239&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25649378">Barthelemy et al. (2015)</a> termed the prelamin A(del90) transcript 'dermopathin' because it was first observed in a patient with restrictive dermopathy (<a href="/entry/275210">275210</a>) by <a href="#48" class="mim-tip-reference" title="Navarro, C. L., De Sandre-Giovannoli, A., Bernard, R., Boccaccio, I., Boyer, A., Genevieve, D., Hadj-Rabia, S., Gaudy-Marqueste, C., Smitt, H. S., Vabres, P., Faivre, L., Verloes, A., Van Essen, T., Flori, E., Hennekam, R., Beemer, F. A., Laurent, N., Le Merrer, M., Cau, P., Levy, N. &lt;strong&gt;Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy.&lt;/strong&gt; Hum. Molec. Genet. 13: 2493-2503, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15317753/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15317753&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddh265&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15317753">Navarro et al. (2004)</a> (see <a href="/entry/150330#0036">150330.0036</a>). Dermopathin excludes the 270 nucleotides of exon 11 and is predicted to cause an internal deletion preserving the prelamin A open reading frame (Gly567_Gln656del). The findings indicated that progerin accumulation is the major pathogenetic mechanism responsible for HGPS-like disorders due to LMNA mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25649378+15317753" 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="Bar, D. Z., Arlt, M. F., Brazier, J. F., Norris, W. E., Campbell, S. E., Chines, P., Larrieu, D., Jackson, S. P., Collins, F. S., Glover, T. W., Gordon, L. B. &lt;strong&gt;A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Med. Genet. 54: 212-216, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/27920058/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;27920058&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmedgenet-2016-104295&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="27920058">Bar et al. (2017)</a> reported an 11.5-year-old girl (patient DB386) who was diagnosed with HGPS at age 10 months, at which time she exhibited typical early stage features; however, she did not develop the total alopecia pathognomonic of classic HGPS, showed less-pronounced mandibular recession, and had milder than expected joint contractures. As she aged, she also displayed better growth than expected, and at age 5.9 years, she had normal blood pressure, no insulinemia or insulin resistance, and no electrocardiographic abnormalities. Sequencing of LMNA exon 11 DNA from blood-derived WBCs and cultured skin fibroblasts revealed 2 different mutations, with blood-derived DNA showing a c.1968+2T-A variant, and all 3 fibroblast DNA isolates showing a c.1968+2T-C variant. Testing for mosaicism demonstrated approximately 50% normal LMNA sequence, with 4.7% c.1968+2T-C and 41.3% c.1968+2T-A. <a href="#2" class="mim-tip-reference" title="Bar, D. Z., Arlt, M. F., Brazier, J. F., Norris, W. E., Campbell, S. E., Chines, P., Larrieu, D., Jackson, S. P., Collins, F. S., Glover, T. W., Gordon, L. B. &lt;strong&gt;A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Med. Genet. 54: 212-216, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/27920058/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;27920058&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmedgenet-2016-104295&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="27920058">Bar et al. (2017)</a> also assessed 2 additional HGPS patients, each heterozygous for 1 of the mutations: a girl (patient DB423) with the c.1968+2T-A mutation, who had a severe HGPS phenotype and died at age 3.5 years; and a boy (patient DB392) with the c.1968+2T-C mutation, who was alive at age 11.5 years with no mandibular recession, moderate alopecia, and moderate lipodystrophy. Based on these genotype/phenotype comparisons, <a href="#2" class="mim-tip-reference" title="Bar, D. Z., Arlt, M. F., Brazier, J. F., Norris, W. E., Campbell, S. E., Chines, P., Larrieu, D., Jackson, S. P., Collins, F. S., Glover, T. W., Gordon, L. B. &lt;strong&gt;A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Med. Genet. 54: 212-216, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/27920058/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;27920058&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmedgenet-2016-104295&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="27920058">Bar et al. (2017)</a> proposed a novel partial phenotypic rescue mechanism, in which patient DB386 had an initial germline mutation c.1968+2T-A, followed by a rescue event during early development, in which the somatic A-C transversion at the same nucleotide provided a selective advantage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27920058" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="pathogenesis" class="mim-anchor"></a>
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<strong>Pathogenesis</strong>
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<p>By light and electron microscopy of fibroblasts from HGPS patients carrying the 1824C-T mutation, <a href="#26" class="mim-tip-reference" title="Goldman, R. D., Shumaker, D. K., Erdos, M. R., Eriksson, M., Goldman, A. E., Gordon, L. B., Gruenbaum, Y., Khuon, S., Mendez, M., Varga, R., Collins, F. S. &lt;strong&gt;Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 101: 8963-8968, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15184648/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15184648&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15184648[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0402943101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15184648">Goldman et al. (2004)</a> found significant changes in nuclear shape, including lobulation of the nuclear envelope, thickening of the nuclear lamina, loss of peripheral heterochromatin, and clustering of nuclear pores. These structural defects worsened as the HGPS cells aged in culture, and their severity correlated with an apparent accumulation of mutant protein, which <a href="#26" class="mim-tip-reference" title="Goldman, R. D., Shumaker, D. K., Erdos, M. R., Eriksson, M., Goldman, A. E., Gordon, L. B., Gruenbaum, Y., Khuon, S., Mendez, M., Varga, R., Collins, F. S. &lt;strong&gt;Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 101: 8963-8968, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15184648/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15184648&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15184648[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0402943101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15184648">Goldman et al. (2004)</a> designated LA delta-50. <a href="#26" class="mim-tip-reference" title="Goldman, R. D., Shumaker, D. K., Erdos, M. R., Eriksson, M., Goldman, A. E., Gordon, L. B., Gruenbaum, Y., Khuon, S., Mendez, M., Varga, R., Collins, F. S. &lt;strong&gt;Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 101: 8963-8968, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15184648/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15184648&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15184648[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0402943101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15184648">Goldman et al. (2004)</a> concluded that expression of LA delta-50 has an age-dependent, cumulative, and ultimately devastating effect on nuclear architecture and function that is responsible for premature aging in HGPS patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15184648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Glynn, M. W., Glover, T. W. &lt;strong&gt;Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition.&lt;/strong&gt; Hum. Molec. Genet. 14: 2959-2969, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16126733/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16126733&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddi326&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16126733">Glynn and Glover (2005)</a> studied the effects of farnesylation inhibition on nuclear phenotypes in cells expressing normal and 1824C-T mutant lamin A. Expression of a GFP-progerin fusion protein in normal fibroblasts caused a high incidence of nuclear abnormalities (as seen in HGPS fibroblasts), and resulted in abnormal nuclear localization of GFP-progerin in comparison with the localization pattern of GFP-lamin A. Expression of a GFP-lamin A fusion containing a mutation preventing the final cleavage step, which caused the protein to remain farnesylated, displayed identical localization patterns and nuclear abnormalities as in HGPS cells and in cells expressing GFP-progerin. Exposure to a farnesyltransferase inhibitor (FTI), PD169541, caused a significant improvement in the nuclear morphology of cells expressing GFP-progerin and in HGPS cells. <a href="#25" class="mim-tip-reference" title="Glynn, M. W., Glover, T. W. &lt;strong&gt;Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition.&lt;/strong&gt; Hum. Molec. Genet. 14: 2959-2969, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16126733/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16126733&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddi326&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16126733">Glynn and Glover (2005)</a> proposed that abnormal farnesylation of progerin may play a role in the cellular phenotype in HGPS cells, and suggested that FTIs may represent a therapeutic option for patients with HGPS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16126733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using various mechanical measurements, including photobleaching assays, biophysical analysis under hypo- and hyperosmotic conditions, and micropipette aspiration, <a href="#12" class="mim-tip-reference" title="Dahl, K. N., Scaffidi, P., Islam, M. F., Yodh, A. G., Wilson, K. L., Misteli, T. &lt;strong&gt;Distinct structural and mechanical properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 103: 10271-10276, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16801550/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16801550&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16801550[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0601058103&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16801550">Dahl et al. (2006)</a> demonstrated that the lamina in HGPS cells has a reduced ability to rearrange after mechanical stress compared to wildtype cells. In response to dynamic changes in the cell, mutant LMNA associated more tightly with the nuclear lamina than wildtype LMNA. Polarization microscopy studies showed that the lamins in HGPS nuclei were birefringent, forming orientationally ordered microdomains with reduced deformability. <a href="#12" class="mim-tip-reference" title="Dahl, K. N., Scaffidi, P., Islam, M. F., Yodh, A. G., Wilson, K. L., Misteli, T. &lt;strong&gt;Distinct structural and mechanical properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 103: 10271-10276, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16801550/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16801550&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16801550[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0601058103&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16801550">Dahl et al. (2006)</a> suggested that the altered mechanical properties of HGPS cells may lead to misexpression of mechanosensitive genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16801550" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Hennekam, R. C. M. &lt;strong&gt;Hutchinson-Gilford progeria syndrome: review of the phenotype.&lt;/strong&gt; Am. J. Med. Genet. 140A: 2603-2624, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16838330/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16838330&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31346&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16838330">Hennekam (2006)</a> noted that the HGPS-like disorder, mandibuloacrodysplasia with type B lipodystrophy (MADB; <a href="/entry/608612">608612</a>), and restrictive dermopathy (<a href="/entry/275210">275210</a>) are both caused by mutation in the ZMPSTE24 gene (<a href="/entry/606480">606480</a>), resulting in abnormal posttranslational processing of lamin A. The author suggested that patients with atypical progeria may have ZMPSTE24 mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16838330" 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="#60" class="mim-tip-reference" title="Wang, J., Robinson, J. F., O&#x27;Neil, C. H., Edwards, J. Y., Williams, C. M., Huff, M. W., Pickering, J. G., Hegele, R. A. &lt;strong&gt;Ankyrin G overexpression in Hutchinson-Gilford progeria syndrome fibroblasts identified through biological filtering of expression profiles.&lt;/strong&gt; J. Hum. Genet. 51: 934-942, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17033732/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17033732&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10038-006-0042-0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17033732">Wang et al. (2006)</a> found that cultured HGPS fibroblasts showed early accelerated growth followed by rapid decline in proliferation in later passages compared to normal cells. HGPS fibroblasts had shrunken cell bodies with coarse cell membranes starting from early passages and showed loss of cell-to-cell growth inhibition with cell clustering. HPGS nuclei also showed multiple morphologic abnormalities compared to normal fibroblasts. Using microarray, RT-PCR, and Western blot analysis, <a href="#60" class="mim-tip-reference" title="Wang, J., Robinson, J. F., O&#x27;Neil, C. H., Edwards, J. Y., Williams, C. M., Huff, M. W., Pickering, J. G., Hegele, R. A. &lt;strong&gt;Ankyrin G overexpression in Hutchinson-Gilford progeria syndrome fibroblasts identified through biological filtering of expression profiles.&lt;/strong&gt; J. Hum. Genet. 51: 934-942, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17033732/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17033732&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10038-006-0042-0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17033732">Wang et al. (2006)</a> found significantly increased (approximately 100-fold) expression of the ANK3 gene (<a href="/entry/600465">600465</a>) in fibroblast cell lines from a patient with HGPS compared to a normal control cell line. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033732" 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="#56" class="mim-tip-reference" title="Varela, I., Pereira, S., Ugalde, A. P., Navarro, C. L., Suarez, M. F., Cau, P., Cadinanos, J., Osorio, F. G., Foray, N., Cobo, J., de Carlos, F., Levy, N., Freije, J. M. P., Lopez-Otin, C. &lt;strong&gt;Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. (Letter)&lt;/strong&gt; Nature Med. 14: 767-772, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18587406/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18587406&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nm1786&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18587406">Varela et al. (2008)</a> found that combined treatment of HGPS cells with both statins and aminobisphosphonates resulted in improved nuclear morphology and decreased accumulation of prelamin A. The mechanism of treatment involved the inhibition of farnesyl pyrophosphate synthesis and prevention of cross-prenylation of prelamin A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18587406" 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="#40" class="mim-tip-reference" title="Liu, G.-H., Barkho, B. Z., Ruiz, S., Diep, D., Qu, J., Yang, S.-L., Panopoulos, A. D., Suzuki, K., Kurian, L., Walsh, C., Thompson, J., Boue, S., Fung, H. L., Sancho-Martinez, I., Zhang, K., Yates, J., III, Belmonte, J. C. I. &lt;strong&gt;Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Nature 472: 221-225, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21346760/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21346760&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21346760[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature09879&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21346760">Liu et al. (2011)</a> reported the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS iPSCs showed absence of progerin, and more importantly, lacked the nuclear envelope and epigenetic alterations normally associated with premature aging. Upon differentiation of HGPS iPSCs, progerin and its aging-associated phenotypic consequences were restored. Specifically, directed differentiation of HGPS iPSCs to vascular smooth muscle cells led to the appearance of premature senescence phenotypes associated with vascular aging. Additionally, their studies identified DNA-dependent protein kinase catalytic subunit (PRKDC; <a href="/entry/600899">600899</a>) as a downstream target of progerin. The absence of nuclear PRKDC holoenzyme correlated with premature as well as physiologic aging. Because progerin also accumulates during physiologic aging, <a href="#40" class="mim-tip-reference" title="Liu, G.-H., Barkho, B. Z., Ruiz, S., Diep, D., Qu, J., Yang, S.-L., Panopoulos, A. D., Suzuki, K., Kurian, L., Walsh, C., Thompson, J., Boue, S., Fung, H. L., Sancho-Martinez, I., Zhang, K., Yates, J., III, Belmonte, J. C. I. &lt;strong&gt;Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Nature 472: 221-225, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21346760/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21346760&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21346760[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature09879&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21346760">Liu et al. (2011)</a> argued that their results provided an in vitro iPSC-based model to study the pathogenesis of human premature and physiologic vascular aging. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21346760" 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 normal cells, heterochromatic, gene-poor, inactive regions of chromatin tend to cluster near the nuclear periphery, while open, active, gene-dense regions cluster in the nuclear interior. <a href="#43" class="mim-tip-reference" title="McCord, R. P., Nazario-Toole, A., Zhang, H., Chines, P. S., Zhan, Y., Erdos, M. R., Collins, F. S., Dekker, J., Cao, K. &lt;strong&gt;Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Genome Res. 23: 260-269, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23152449/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23152449&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23152449[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1101/gr.138032.112&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23152449">McCord et al. (2013)</a> found that HGPS skin fibroblasts lost this compartmentalization at later passages. Loss of compartmentalization was preceded by loss of H3K27 trimethylation in gene-poor regions, gain of H3K27 trimethylation in gene-rich regions, and detachment of chromatin from the lamina visible by electron microscopy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23152449" 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 progeria, the accumulation of farnesyl-prelamin A disrupts the structural scaffolding for the cell nucleus, leading to misshapen nuclei. Farnesyltransferase inhibitors (FTIs) can reverse this cellular abnormality (e.g., <a href="#42" class="mim-tip-reference" title="Mallampalli, M. P., Huyer, G., Bendale, P., Gelb, M. H., Michaelis, S. &lt;strong&gt;Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 102: 14416-14421, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16186497/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16186497&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16186497[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0503712102&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16186497">Mallampalli et al., 2005</a>). <a href="#22" class="mim-tip-reference" title="Fong, L. G., Frost, D., Meta, M., Qiao, X., Yang, S. H., Coffinier, C., Young, S. G. &lt;strong&gt;A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria.&lt;/strong&gt; Science 311: 1621-1623, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16484451/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16484451&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.1124875&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16484451">Fong et al. (2006)</a> tested the efficacy of an FTI (ABT-100) in Zmpste24-deficient mice, a mouse model of progeria. The FTI-treated mice exhibited improved body weight, grip strength, bone integrity, and percent survival at 20 weeks of age. <a href="#22" class="mim-tip-reference" title="Fong, L. G., Frost, D., Meta, M., Qiao, X., Yang, S. H., Coffinier, C., Young, S. G. &lt;strong&gt;A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria.&lt;/strong&gt; Science 311: 1621-1623, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16484451/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16484451&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.1124875&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16484451">Fong et al. (2006)</a> concluded that FTIs may have beneficial effects in humans with progeria. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16186497+16484451" 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="#62" class="mim-tip-reference" title="Yang, S. H., Meta, M., Qiao, X., Frost, D., Bauch, J., Coffinier, C., Majumdar, S., Bergo, M. O., Young, S. G., Fong, L. G. &lt;strong&gt;A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation.&lt;/strong&gt; J. Clin. Invest. 116: 2115-2121, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16862216/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16862216&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16862216[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI28968&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16862216">Yang et al. (2006)</a> generated mice with a targeted HGPS mutation (Lmna HG/+) and observed phenotypes similar to those in human HGPS patients, including retarded growth, reduced amounts of adipose tissue, micrognathia, osteoporosis, and osteolytic lesions in bone, which caused spontaneous rib fractures in the mutant mice. Treatment with an FTI increased adipose tissue mass, improved body weight curves, reduced the number of rib fractures, and improved bone mineralization and bone cortical thickness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16862216" 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="#57" class="mim-tip-reference" title="Varga, R., Eriksson, M., Erdos, M. R., Olive, M., Harten, I., Kolodgie, F., Capell, B. C., Cheng, J., Faddah, D., Perkins, S., Avallone, H., San, H., Qu, X., Ganesh, S., Gordon, L. B., Virmani, R., Wight, T. N., Nabel, E. G., Collins, F. S. &lt;strong&gt;Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 103: 3250-3255, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16492728/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16492728&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16492728[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0600012103&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16492728">Varga et al. (2006)</a> created a mouse model for progeria harboring the common human G608G LMNA mutation (<a href="/entry/150330#0022">150330.0022</a>). Mutant mice showed striking arterial changes, including progressive loss of vascular smooth muscle cells in the medial layer, elastic fiber breakage, and proteoglycan and collagen deposition in a pattern very similar to that seen in children with HGPS. Arterial calcification, adventitial thickening, and severe loss of vascular smooth muscle cells was observed in older mutant mice. Older mutant mice also showed impaired blood pressure regulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16492728" 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 conditional transgenic mice with a human LMNA mutation, <a href="#55" class="mim-tip-reference" title="Sagelius, H., Rosengardten, Y., Schmidt, E., Sonnabend, C., Rozell, B., Eriksson, M. &lt;strong&gt;Reversible phenotype in a mouse model of Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Med. Genet. 45: 794-801, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18708427/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18708427&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2008.060772&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18708427">Sagelius et al. (2008)</a> observed external features of the syndrome, including hair thinning and skin crusting, at postnatal week 4. After phenotype development, transgenic expression was turned off, and there was a rapid improvement of the phenotype within 4 weeks of transgenic suppression. After 13 weeks, pathologic examination showed that skin from the mutant mice was almost indistinguishable from wildtype skin, and there was also improvement in teeth. <a href="#55" class="mim-tip-reference" title="Sagelius, H., Rosengardten, Y., Schmidt, E., Sonnabend, C., Rozell, B., Eriksson, M. &lt;strong&gt;Reversible phenotype in a mouse model of Hutchinson-Gilford progeria syndrome.&lt;/strong&gt; J. Med. Genet. 45: 794-801, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18708427/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18708427&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2008.060772&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18708427">Sagelius et al. (2008)</a> concluded that, in these tissues, expression of the progeria mutation did not cause irreversible damage and that reversal of disease phenotype is possible. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18708427" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Ayres, S. C., Mihan, R. &lt;strong&gt;Progeria: a possible therapeutic approach. (Letter)&lt;/strong&gt; JAMA 227: 1381-1382, 1974.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4406015/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4406015&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/jama.1974.03230250013009&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4406015">Ayres and Mihan (1974)</a> suggested that a fault in vitamin E metabolism may be at the root of progeria and recommended vitamin E therapy for its antioxidant effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4406015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Brown1980" class="mim-tip-reference" title="Brown, W. T., Darlington, G. J. &lt;strong&gt;Thermolabile enzymes in progeria and Werner syndrome: evidence contrary to the protein error hypothesis.&lt;/strong&gt; Am. J. Hum. Genet. 32: 614-619, 1980.">Brown and Darlington (1980)</a>; <a href="#Goldstein1975" class="mim-tip-reference" title="Goldstein, S., Moerman, E. J. &lt;strong&gt;Heat-labile enzymes in skin fibroblasts from subjects with progeria.&lt;/strong&gt; New Eng. J. Med. 292: 1305-1309, 1975.">Goldstein and Moerman (1975)</a>; <a href="#Harley1981" class="mim-tip-reference" title="Harley, C. B., Goldstein, S., Posner, B. I., Guyda, H. &lt;strong&gt;Decreased sensitivity of old and progeric human fibroblasts to a preparation of factors with insulinlike activity.&lt;/strong&gt; J. Clin. Invest. 68: 988-994, 1981.">Harley et
al. (1981)</a>; <a href="#Rautenstrauch1977" class="mim-tip-reference" title="Rautenstrauch, T., Snigula, F., Krieg, T., Gay, S., Muller, P. K. &lt;strong&gt;Progeria: a cell culture study and clinical report of a familial incidence.&lt;/strong&gt; Europ. J. Pediat. 124: 101-112, 1977.">Rautenstrauch et al. (1977)</a>; <a href="#Viegas1974" class="mim-tip-reference" title="Viegas, J., Souza, P. L. R., Salzano, F. M. &lt;strong&gt;Progeria in twins.&lt;/strong&gt; J. Med. Genet. 11: 384-386, 1974.">Viegas et al. (1974)</a>
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<a id="Ayres1974" class="mim-anchor"></a>
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Ayres, S. C., Mihan, R.
<strong>Progeria: a possible therapeutic approach. (Letter)</strong>
JAMA 227: 1381-1382, 1974.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4406015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4406015</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4406015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/jama.1974.03230250013009" target="_blank">Full Text</a>]
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<a id="Bar2017" class="mim-anchor"></a>
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Bar, D. Z., Arlt, M. F., Brazier, J. F., Norris, W. E., Campbell, S. E., Chines, P., Larrieu, D., Jackson, S. P., Collins, F. S., Glover, T. W., Gordon, L. B.
<strong>A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome.</strong>
J. Med. Genet. 54: 212-216, 2017.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27920058/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27920058</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27920058" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmedgenet-2016-104295" target="_blank">Full Text</a>]
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<a id="Barthelemy2015" class="mim-anchor"></a>
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Barthelemy, F., Navarro, C., Fayek, R., Da Silva, N., Roll, P., Sigaudy, S., Oshima, J., Bonne, G., Papadopoulou-Legbelou, K., Evangeliou, A. E., Spilioti, M., Lemerrer, M., Wevers, R. A., Morava, E., Robaglia-Schlupp, A., Levy, N., Bartoli, M., De Sandre-Giovannoli, A.
<strong>Truncated prelamin A expression in HGPS-like patients: a transcriptional study.</strong>
Europ. J. Hum. Genet. 23: 1051-1061, 2015.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25649378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25649378</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25649378[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=25649378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ejhg.2014.239" target="_blank">Full Text</a>]
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<a id="Brown1990" class="mim-anchor"></a>
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Brown, W. T., Abdenur, J., Goonewardena, P., Alemzadeh, R., Smith, M., Friedman, S., Cervantes, C., Bandyopadhyay, S., Zaslav, A., Kunaporn, S., Serotkin, A., Lifshitz, F.
<strong>Hutchinson-Gilford progeria syndrome: clinical, chromosomal and metabolic abnormalities. (Abstract)</strong>
Am. J. Hum. Genet. 47 (suppl.): A50 only, 1990.
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<a id="Brown1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brown, W. T., Darlington, G. J., Arnold, A., Fotino, M.
<strong>Detection of HLA antigens on progeria syndrome fibroblasts.</strong>
Clin. Genet. 17: 213-219, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6988117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6988117</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6988117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1980.tb00135.x" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
<a id="Brown1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brown, W. T., Darlington, G. J.
<strong>Thermolabile enzymes in progeria and Werner syndrome: evidence contrary to the protein error hypothesis.</strong>
Am. J. Hum. Genet. 32: 614-619, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6930821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6930821</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6930821" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Brown1979" class="mim-anchor"></a>
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Brown, W. T.
<strong>Human mutations affecting aging--a review.</strong>
Mech. Aging Dev. 9: 325-336, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/155763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">155763</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=155763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0047-6374(79)90109-x" target="_blank">Full Text</a>]
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<a id="Brown2004" class="mim-anchor"></a>
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<p class="mim-text-font">
Brown, W. T.
<strong>Personal Communication.</strong>
Staten Island, N.Y. 1/12/2004.
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<a id="Cao2003" class="mim-anchor"></a>
<div class="">
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Cao, H., Hegele, R. A.
<strong>LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).</strong>
J. Hum. Genet. 48: 271-274, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12768443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12768443</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12768443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s10038-003-0025-3" target="_blank">Full Text</a>]
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<a id="Cao2011" class="mim-anchor"></a>
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Cao, K., Graziotto, J. J., Blair, C. D., Mazzulli, J. R., Erdos, M. R., Krainc, D., Collins, F. S.
<strong>Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.</strong>
Sci. Transl. Med. 3: 89ra58, 2011. Note: Electronic Article.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21715679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21715679</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21715679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/scitranslmed.3002346" target="_blank">Full Text</a>]
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<a id="Chen2003" class="mim-anchor"></a>
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<p class="mim-text-font">
Chen, L., Lee, L., Kudlow, B. A., Dos Santos, H. G., Sletvold, O., Shafeghati, Y., Botha, E. G., Garg, E., Hanson, N. B., Martin, G. M., Mian, I. S., Kennedy, B. K., Oshima, J.
<strong>LMNA mutations in atypical Werner's syndrome.</strong>
Lancet 362: 440-445, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12927431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12927431</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12927431" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/S0140-6736(03)14069-X" target="_blank">Full Text</a>]
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<a id="Dahl2006" class="mim-anchor"></a>
<div class="">
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Dahl, K. N., Scaffidi, P., Islam, M. F., Yodh, A. G., Wilson, K. L., Misteli, T.
<strong>Distinct structural and mechanical properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome.</strong>
Proc. Nat. Acad. Sci. 103: 10271-10276, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16801550/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16801550</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16801550[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=16801550" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.0601058103" target="_blank">Full Text</a>]
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<a id="De Martinville1980" class="mim-anchor"></a>
<div class="">
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De Martinville, B., Sorin, M., Briard, M. L., Frezal, J.
<strong>Progeria de Gilford-Hutchinson a debut neonatal chez des jumeaux monozygotes.</strong>
Arch. Franc. Pediat. 37: 679-681, 1980.
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<a id="de Paula Rodrigues2002" class="mim-anchor"></a>
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de Paula Rodrigues, G. H., das Eiras Tamega, I., Duque, G., Spinola Dias Neto, V.
<strong>Severe bone changes in a case of Hutchinson-Gilford syndrome.</strong>
Ann. Genet. 45: 151-155, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12381448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12381448</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12381448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0003-3995(02)01119-x" target="_blank">Full Text</a>]
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<a id="De Sandre-Giovannoli2003" class="mim-anchor"></a>
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De Sandre-Giovannoli, A., Bernard, R., Cau, P., Navarro, C., Amiel, J., Boccaccio, I., Lyonnet, S., Stewart, C. L., Munnich, A., Le Merrer, M., Levy, N.
<strong>Lamin A truncation in Hutchinson-Gilford progeria.</strong>
Science 300: 2055 only, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12702809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12702809</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12702809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.1084125" target="_blank">Full Text</a>]
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<a id="DeBusk1972" class="mim-anchor"></a>
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DeBusk, F. L.
<strong>The Hutchinson-Gilford progeria syndrome.</strong>
J. Pediat. 80: 697-724, 1972.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4552697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4552697</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4552697" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(72)80229-4" target="_blank">Full Text</a>]
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<a id="Delgado Luengo2002" class="mim-anchor"></a>
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<p class="mim-text-font">
Delgado Luengo, W.., Rojas Martinez, A., Ortiz Lopez, R., Martinez Basalo, C., Rojas-Atencio, A., Quintero, M., Borjas, L., Morales-Machin, A., Gonzalez Ferrer, S., Pineda Bernal, L., Canizalez-Tarazona, J., Pena, J., Delgado Luengo, J., Chacin Hernandez, J., Chang, J. C.
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[<a href="https://doi.org/10.1002/ajmg.1320310302" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.0503712102" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1101/gr.138032.112" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.32627" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJMoa0706898" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddh265" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0002-9343(86)90196-8" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320360411" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.2004.019661" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.2008.060772" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nm1786" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddl172" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s10038-006-0042-0" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16862216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16862216</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16862216[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=16862216" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI28968" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 01/26/2018
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Marla J. F. O'Neill - updated : 11/03/2017<br>Cassandra L. Kniffin - updated : 10/27/2015<br>Cassandra L. Kniffin - updated : 9/4/2015<br>Patricia A. Hartz - updated : 10/14/2014<br>Ada Hamosh - updated : 6/4/2014<br>Ada Hamosh - updated : 10/11/2011<br>Ada Hamosh - updated : 6/7/2011<br>Marla J. F. O'Neill - updated : 10/19/2010<br>Cassandra L. Kniffin - updated : 1/11/2010<br>George E. Tiller - updated : 5/13/2009<br>Cassandra L. Kniffin - updated : 2/11/2009<br>Cassandra L. Kniffin - updated : 7/22/2008<br>Victor A. McKusick - updated : 3/10/2008<br>Cassandra L. Kniffin - updated : 12/17/2007<br>Marla J. F. O'Neill - updated : 3/8/2007<br>Victor A. McKusick - updated : 2/23/2007<br>Cassandra L. Kniffin - updated : 8/9/2006<br>Ada Hamosh - updated : 4/14/2006<br>Marla J. F. O'Neill - updated : 5/23/2005<br>Victor A. McKusick - updated : 3/8/2005<br>Victor A. McKusick - updated : 11/9/2004<br>Marla J. F. O'Neill - updated : 11/3/2004<br>Patricia A. Hartz - updated : 10/27/2004<br>Victor A. McKusick - updated : 10/20/2004<br>Victor A. McKusick - updated : 2/17/2004<br>Ada Hamosh - updated : 4/29/2003<br>Cassandra L. Kniffin - updated : 4/28/2003<br>Ada Hamosh - updated : 4/23/2003<br>Ada Hamosh - updated : 4/16/2003<br>Victor A. McKusick - updated : 1/10/2003<br>Victor A. McKusick - updated : 1/10/2003<br>Victor A. McKusick - updated : 12/28/1999<br>Victor A. McKusick - updated : 2/26/1999
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Victor A. McKusick : 6/2/1986
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carol : 01/26/2018
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carol : 11/16/2017<br>carol : 11/03/2017<br>carol : 08/26/2016<br>carol : 10/29/2015<br>ckniffin : 10/27/2015<br>carol : 9/9/2015<br>ckniffin : 9/4/2015<br>alopez : 3/17/2015<br>mgross : 10/14/2014<br>alopez : 6/4/2014<br>terry : 8/31/2012<br>terry : 3/26/2012<br>carol : 2/29/2012<br>alopez : 10/11/2011<br>alopez : 6/9/2011<br>alopez : 6/9/2011<br>terry : 6/7/2011<br>carol : 5/25/2011<br>carol : 10/19/2010<br>terry : 10/13/2010<br>carol : 1/15/2010<br>ckniffin : 1/11/2010<br>wwang : 6/25/2009<br>terry : 6/3/2009<br>terry : 5/13/2009<br>wwang : 4/6/2009<br>ckniffin : 2/11/2009<br>wwang : 7/25/2008<br>ckniffin : 7/22/2008<br>alopez : 3/19/2008<br>terry : 3/10/2008<br>ckniffin : 12/17/2007<br>wwang : 4/2/2007<br>ckniffin : 3/16/2007<br>wwang : 3/12/2007<br>terry : 3/8/2007<br>wwang : 3/1/2007<br>terry : 2/23/2007<br>wwang : 8/11/2006<br>ckniffin : 8/9/2006<br>alopez : 4/18/2006<br>terry : 4/14/2006<br>wwang : 6/8/2005<br>wwang : 6/1/2005<br>terry : 5/23/2005<br>carol : 3/8/2005<br>carol : 3/8/2005<br>terry : 2/21/2005<br>carol : 12/8/2004<br>alopez : 11/15/2004<br>terry : 11/9/2004<br>tkritzer : 11/4/2004<br>terry : 11/3/2004<br>mgross : 10/27/2004<br>terry : 10/20/2004<br>carol : 2/17/2004<br>alopez : 7/7/2003<br>alopez : 5/28/2003<br>alopez : 5/9/2003<br>alopez : 4/30/2003<br>terry : 4/29/2003<br>carol : 4/28/2003<br>ckniffin : 4/28/2003<br>alopez : 4/23/2003<br>joanna : 4/23/2003<br>carol : 4/17/2003<br>alopez : 4/16/2003<br>terry : 4/16/2003<br>tkritzer : 1/23/2003<br>tkritzer : 1/13/2003<br>terry : 1/10/2003<br>terry : 1/10/2003<br>carol : 12/4/2002<br>tkritzer : 12/3/2002<br>terry : 11/27/2002<br>carol : 12/29/1999<br>terry : 12/28/1999<br>carol : 3/1/1999<br>terry : 2/26/1999<br>mimadm : 2/25/1995<br>supermim : 3/16/1992<br>carol : 4/11/1991<br>carol : 3/28/1991<br>carol : 12/5/1990<br>carol : 11/26/1990
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<strong>#</strong> 176670
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HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS
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<em>Alternative titles; symbols</em>
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PROGERIA
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Other entities represented in this entry:
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PROGERIA SYNDROME, CHILDHOOD-ONSET, INCLUDED
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<strong>SNOMEDCT:</strong> 238870004; &nbsp;
<strong>ICD10CM:</strong> E34.8; &nbsp;
<strong>ORPHA:</strong> 740; &nbsp;
<strong>DO:</strong> 3911; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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1q22
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Hutchinson-Gilford progeria
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176670
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Autosomal dominant
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3
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LMNA
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150330
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because both classic infantile-onset and later childhood-onset Hutchinson-Gilford progeria syndrome (HGPS) are caused by de novo heterozygous mutation in the lamin A gene (LMNA; 150330) on chromosome 1q22.</p>
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<strong>Description</strong>
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<p>Hutchinson-Gilford progeria syndrome is a rare disorder characterized by short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early death. Cognitive development is normal. Onset is usually within the first year of life (review by Hennekam, 2006). The designation Hutchinson-Gilford progeria syndrome appears to have been first used by DeBusk (1972). </p><p>A subset of patients with heterozygous mutations in the LMNA gene and a phenotype similar to HGPS have shown onset of the disorder in late childhood or in the early teenage years, and have longer survival than observed in classic HGPS (Chen et al., 2003; Hegele, 2003). </p><p>Other disorders with a less severe, but overlapping phenotype include mandibuloacral dysplasia (MADA; 248370), an autosomal disorder caused by homozygous or compound heterozygous mutations in the LMNA gene, dilated cardiomyopathy with hypergonadotropic hypogonadism (212112), caused by heterozygous mutation in the LMNA gene, and Werner syndrome (277700), an autosomal recessive progeroid syndrome caused by homozygous or compound heterozygous mutations in the RECQL2 gene (604611).</p>
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<strong>Clinical Features</strong>
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<p>Hastings Gilford (1904) gave the name progeria to this disorder in an article in which he also assigned the term ateleiosis to a pituitary growth hormone deficiency (262400). He provided no photographs of progeria and indicated that 'only two well-marked instances have so far been recorded.' Death from angina pectoris at age 18 years was noted. Jonathan Hutchinson (1886) had previously written about the disorder (McKusick, 1952). Hutchinson's report was accompanied by a photograph of his patient at the age of 15.5 years showing the stereotypic phenotype of this disorder. Hutchinson emphasized the lack of hair but the other features were evident: disproportionately large head, 'pinched' facial features, lipodystrophy, incomplete extension at the knees and elbows indicating stiffness of joints, and generally a senile appearance. </p><p>Paterson (1922) recorded the cases of 2 possibly affected brothers whose parents were first cousins. Photographs were not published and the diagnosis is not completely certain. The full report was simply the following: 'A boy, aged 8 years. Condition has been present since birth... There are 4 children in the family; the girls are unaffected, both boys are affected. The senile condition of the skin and facies should be noted. The vessels show arteriosclerosis. (There is almost complete absence of subcutaneous fat.)'</p><p>Ogihara et al. (1986) described a Japanese patient with progeria who survived to age 45, dying of myocardial infarction. Clinically, he seemed typical except for the unusually long survival. According to reviews of the literature, the age at death ranges from 7 to 27.5 years, with a median age of 13.4 years. Dyck et al. (1987) reported coronary artery bypass surgery and percutaneous transluminal angioplasty in a 14-year-old girl with this disorder. </p><p>The 2 brothers reported as having progeria by Parkash et al. (1990) probably had mandibuloacral dysplasia (MADA; 248370). Fatunde et al. (1990) described a family in which 3 of 6 sibs had progeria. A seventh sib, who had died before the time of study, may have been affected. </p><p>Three cases of neonatal HGPS were reported in France (De Martinville et al., 1980; Labeille et al., 1987). All 3 patients died early, 2 on the first day of life and the other patient at 20 months of age. Unlike classic HGPS, however, none of the 3 presented clinical signs of coronary occlusion. </p><p>De Paula Rodrigues et al. (2002) reported details of the involvement of bones and joints in a seemingly typical example of progeria in an 8-year-old girl. </p><p>Hennekam (2006) provided an exhaustive review of the phenotype of HGPS, based on data from 10 of his own cases and 132 cases from the literature. </p><p>Merideth et al. (2008) comprehensively studied 15 children between 1 and 17 years of age, representing nearly half of the world's known patients with Hutchinson-Gilford progeria syndrome. The previously described features were documented. Previously unrecognized findings included prolonged prothrombin times, elevated platelet counts and serum phosphorus levels, low-frequency conductive hearing loss, and functional oral deficits. Growth impairment was not related to inadequate nutrition, insulin unresponsiveness, or growth hormone deficiency. Growth hormone treatment in a few patients increased height growth by 10% and weight growth by 50%. Cardiovascular studies revealed diminishing vascular function with age, including elevated blood pressure, reduced vascular compliance, decreased ankle-brachial indices, and adventitial thickening. The ankle-brachial index was used to measure the difference in blood pressure between the legs and arms in 11 children. The index was abnormal in 2 patients, indicating arterial disease in the legs. </p><p><strong><em>Childhood-Onset HGPS</em></strong></p><p>
Chen et al. (2003) found that 26 (20%) of 129 probands referred to their international registry for molecular diagnosis of the autosomal recessive progeroid disorder Werner syndrome (277700) did not have mutations in the RECQL2 gene (604611). Sequencing of the LMNA gene in these individuals found that 4 (15%) had heterozygous mutations: A57P (150330.0030), R133L (in 2 persons) (150330.0027), and L140R (150330.0031), all of which altered relatively conserved residues within lamin A/C. Fibroblasts from the patient with the L140R mutation had a substantially enhanced proportion of nuclei with altered morphology and mislocalized lamins. These individuals had a more severe phenotype than those with RECQL2-associated Werner syndrome. Although Chen et al. (2003) designated these patients as having 'atypical Werner syndrome,' Hegele (2003) suggested that the patients more likely had late-onset Hutchinson-Gilford progeria syndrome. Hegele (2003) reviewed the clinical features of the 4 patients with LMNA mutations reported by Chen et al. (2003), and stated that the designation of 'atypical Werner syndrome' appeared somewhat insecure. He noted that the comparatively young ages of onset in the patients with mutant LMNA would be just as consistent with late-onset HGPS as with early-onset Werner syndrome. These patients also expressed features of nonprogeroid laminopathies, including insulin resistance (FPLD2; 151660), dilated cardiomyopathy (115200), and phalangeal osteosclerosis (MADA; 248370). Hegele (2003) suggested that genomic DNA analysis can help draw a diagnostic line that clarifies potential overlap between older patients with Hutchinson-Gilford syndrome and younger patients with Werner syndrome, and that therapies may depend on precise molecular classification. </p><p>McPherson et al. (2009) noted phenotypic similarities between the patient studied by Chen et al. (2003) with the A57P LMNA mutation and 2 unrelated patients with heterozygosity for an adjacent mutation in the LMNA gene, L59R (150330.0052). Features common to these 3 patients included premature ovarian failure, dilated cardiomyopathy, lipodystrophy, and progressive facial and skeletal changes involving micrognathia and sloping shoulders, but not acroosteolysis. Although the appearance of these patients was somewhat progeroid, none had severe growth failure, alopecia, or rapidly progressive atherosclerosis, and McPherson et al. (2009) suggested that the phenotype represents a distinct laminopathy (dilated cardiomyopathy and hypergonadotropic hypogonadism, 212112). </p><p>Hisama et al. (2011) reported a nonconsanguineous family in which 2 sibs and their mother had adult-onset coronary artery disease with progeroid features. The patients had short stature and a progeroid appearance as adults, including loss of subcutaneous fat, hair loss, tooth loss, low bone density, and beaked nose. Cardiac features included hyperlipidemia and hypercholesterolemia resulting in severe atherosclerosis necessitating bypass surgery in 2 patients. Two patients also developed diabetes. None of the patients had cataracts. A 48-year-old woman from an unrelated family had a similar phenotype, with short stature, progeroid appearance, tight and atrophic skin, and hyperlipidemia with coronary artery disease. She died of surgical complications after bypass surgery. </p><p>Kane et al. (2013) reported a family in which 5 individuals had a progeroid syndrome with prominent cutaneous and cardiovascular manifestations. The proband and her sister were described in detail. Both were normal at birth, but lost eyebrows and eyelashes in childhood. In their late twenties, both showed a progeroid appearance and developed exertional dyspnea associated with mitral valve calcification and stenosis necessitating valve replacement; the proband also had aortic stenosis. The proband developed occlusion of the coronary arteries and died of acute myocardial infarction at age 44; her sister died of intracranial hemorrhage at age 34. Both women also had several primary malignancies, including basal and squamous cell carcinomas, papillary renal carcinoma, and carcinoid tumor. Family history revealed a father, paternal uncle, and paternal grandfather with premature aging and significant cardiac disease resulting in death between ages 29 and 44 years. Kane et al. (2013) proposed the name LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. </p><p>Barthelemy et al. (2015) reported a patient with late-onset HGPS. He was first seen at age 30 years, when he showed a progeroid appearance with facial dysmorphism, lipoatrophy, thin skin, hair loss, and brittle nails. He had hypertriglyceridemia, osteolysis of the distal phalanges, and diffuse and severe atherosclerosis and aortic stenosis necessitating cardiac surgery. He died of surgical complications at age 35. An unrelated patient presented at age 12 years with short stature and a progeroid appearance, including atrophic skin, alopecia, amyotrophy, lipoatrophy, and distal phalangeal osteolysis. He developed aortic valve stenosis and hypertrophic cardiomyopathy resulting in death at age 17. </p>
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<strong>Biochemical Features</strong>
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<p>In cultured skin fibroblasts of patients with progeria, Goldstein and Moerman (1978) demonstrated an increased fraction of heat-labile enzymes and other altered proteins. Freshly obtained cells, namely, erythrocytes, showed similar heat-lability of G6PD and 6-phosphogluconate dehydrogenases in a girl with progeria. Both parents showed intermediate values, consistent with recessive inheritance. Normal HLA antigens were found by Brown et al. (1980). </p><p>Cao et al. (2011) reported the effect of rapamycin on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the formation of insoluble progerin aggregates and induced clearance through autophagic mechanisms in normal fibroblasts. Cao et al. (2011) concluded that their findings suggested an additional mechanism for the beneficial effects of rapamycin on longevity and encouraged the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS. </p><p>Larrieu et al. (2014) identified a small molecule that they called 'remodelin' that improved nuclear architecture, chromatin organization, and fitness of both human LMNA (150330)-depleted cells and HGPS-derived patient cells, and decreased markers of DNA damage in these cells. Using a combination of chemical, cellular, and genetic approaches, Larrieu et al. (2014) identified NAT10 (609221) as the target of remodelin that mediated nuclear shape rescue in laminopathic cells via microtubule reorganization. Larrieu et al. (2014) concluded that these findings provided insights into how NAT10 affects nuclear architecture and suggested alternative strategies for treating laminopathies and aging. </p>
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<strong>Inheritance</strong>
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<p>The majority of patients with HGPS have de novo heterozygous dominant mutations in the LMNA gene. Presumably, patients with the disorder do not survive long enough to reproduce (Eriksson et al., 2003; Cao and Hegele, 2003). </p><p>DeBusk (1972) maintained that of 19 cases reported to that date in which consanguinity was sought, in only 3 were the parents related. He suggested that progeria could conceivably be dominant and the rare instances of affected sibs be the result of germinal mosaicism. </p><p>DeBusk (1972) and Jones et al. (1975) reported a paternal age effect, supporting autosomal dominant inheritance. In 20 cases in which parental age was known, the mean paternal and maternal ages were 35.6 and 28.8 years, respectively, and the median ages 31 and 28, respectively. In 7 U.S. cases, the mean paternal age was 37.1. On the basis of the paternal age effect, the low frequency of parental consanguinity, and the report of progeric monozygotic twins of 14 normal sibs, Brown (1979) favored autosomal dominant inheritance, with most cases resulting from a de novo, new, mutation. </p><p>In a patient with Hutchinson-Gilford progeria, Wuyts et al. (2005) identified a heterozygous mutation in the LMNA gene (G608G; 150330.0022). In lymphocyte DNA from the parents, normal wildtype alleles were observed in the father, but a low signal corresponding to the mutant allele was detected in the mother's DNA. A segregation study confirmed that the patient's mutation was transmitted from the mother, who showed germline and somatic mosaicism without clinical manifestations of HGPS. </p><p><strong><em>Reports Suggesting Autosomal Recessive Inheritance</em></strong></p><p>
Recessive inheritance was suggested by the report from Egypt of affected sisters, children of first cousins (Gabr et al., 1960). Erecinski et al. (1961) described photographically typical progeria in 2 brothers. Among the 9 offspring of 2 sisters, Rava (1967) found 6 affected. </p><p>Maciel (1988) reported an inbred Brazilian family in which presumed Hutchinson-Gilford progeria syndrome had occurred in members of 2 sibships related as first cousins once removed. Although autosomal recessive inheritance was unmistakable, the disorder was not definitively HGPS. </p><p>Khalifa (1989) described a consanguineous Libyan family in which 2 males and 1 female in 2 sibships related as cousins had seemingly typical Hutchinson-Gilford progeria. Repeated nonhealing fractures were the presenting manifestation in the proband. </p><p>Verstraeten et al. (2006) reported a 2-year-old Dutch boy with features of HGPS who was compound heterozygous for 2 mutations in the LMNA gene. After the age of 1 year, he showed failure to thrive, poor growth, and hair loss. Clinical features included prominent forehead, prominent veins, narrow nasal bridge, small mouth, lipodystrophy, and dental crowding. He also had significant shortening of the distal phalanges with osteolysis and tufting, as well as osteoresorption of the distal ends of the clavicles. Some of these features were more consistent with mandibuloacral dysplasia. Fibroblasts derived from the patient showed irregularly shaped nuclei with blebs, honeycomb figures, large and poorly defined protrusions, and intra/trans-nuclear tubule-like structures. There was no accumulation of prelamin A, as usually observed in typical HGPS. A clinically unaffected sister was heterozygous for 1 of the mutations, and each clinically unaffected parent was heterozygous for 1 of the mutations. A smaller percentage of fibroblasts derived from the parents showed the nuclear abnormalities that were present in the proband. </p>
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<strong>Cytogenetics</strong>
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<p>Brown et al. (1990) described identical twins with progeria who developed heart failure at the age of 8 and died within 1 month of each other. Cytogenetic analysis showed an inverted insertion in the long arm of chromosome 1 in 70% of cells. Brown et al. (1990) suggested that a gene for progeria may be located on chromosome 1. Evidence for possible bioinactive growth hormone was presented with a suggestion of treatment of progeria with growth hormone.</p><p>In a 9-year-old patient with a classic clinical picture of Hutchinson-Gilford progeria, Delgado Luengo et al. (2002) found an interstitial deletion of chromosome 1q23. Because a perturbation in glycosylation in connective tissue had been demonstrated in patients with this condition, they suggested that the defect may reside in the B4GALT3 gene (604014), which maps to 1q23. </p><p>Lewis (2003) suggested that the defect causing progeria might reside in the proline/arginine-rich end leucine-rich repeat protein gene (PRELP; 601914), which maps to chromosome 1q32 and is a small leucine-rich proteoglycan that binds type I collagen to basement membranes and type II collagen to cartilage. </p>
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<strong>Population Genetics</strong>
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<p>Hennekam (2006) stated that the incidence of HGPS was 1 per 8 million newborns in the US between 1915 and 1967 and 1 per 4 million newborns in the Netherlands between 1900 and 2005. Patients have been reported from all continents and all ethnic backgrounds. </p>
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
<p>Eriksson et al. (2003) reported de novo point mutations in lamin A (150330) causing Hutchinson-Gilford progeria syndrome. The HGPS gene was initially localized to chromosome 1q by observing 2 cases of uniparental isodisomy of 1q, and 1 case with a 6-Mb paternal interstitial deletion. Eighteen of 20 classic cases of HGPS harbored the identical de novo single-base substitution, a C-to-T transition resulting in a silent gly-to-gly change at codon 608 within exon 11 (G608G; 150330.0022). One additional case was identified with a different substitution within the same codon (150330.0023). Both of these mutations were shown to result in activation of a cryptic splice site within exon 11 of the lamin A gene, resulting in production of a protein product that deletes 50 amino acids near the C terminus. This prelamin A still retains the CAAX box but lacks the site for endoproteolytic cleavage. Immunofluorescence of HGPS fibroblasts with antibodies directed against lamin A revealed that many cells showed visible abnormalities of the nuclear membrane. </p><p>Cao and Hegele (2003) studied cell lines from 7 HGPS probands. Five carried the common mutation within exon 11 of LMNA, which they termed 2036C-T (150330.0022). In 1 of 7 patients, they identified the G608S mutation (150330.0023). Cao and Hegele (2003) confirmed the findings of Eriksson et al. (2003) using the same cell lines. In 1 patient with an HGPS phenotype who was 28 years old at the time that DNA was obtained, Cao and Hegele (2003) identified compound heterozygosity for 2 missense mutations in the LMNA gene (150330.0025 and 150330.0026); this patient was later determined (Brown, 2004) to have mandibuloacral dysplasia. </p><p>De Sandre-Giovannoli et al. (2003) identified the exon 11 cryptic splice site activation mutation (1824C-T+1819-1968del; 150330.0022) in 2 HGPS patients. Immunocytochemical analyses of lymphocytes from 1 patient using specific antibodies directed against lamin A/C, lamin A, and lamin B1 showed that most cells had strikingly altered nuclear sizes and shapes, with envelope interruptions accompanied by chromatin extrusion. Lamin A was detected in 10 to 20% of HGPS lymphocytes. Only lamin C was present in most cells, and lamin B1 was found in the nucleoplasm, suggesting that it had dissociated from the nuclear envelope due to the loss of lamin A. Western blot analysis showed 25% of normal lamin A levels, and no truncated form was detected. </p><p>In 4 affected members of a consanguineous family from north India, Plasilova et al. (2004) with features of both MADA (248370) and HGPS resulting from a homozygous missense mutation in the LMNA gene (150330.0033). Plasilova et al. (2004) suggested that autosomal recessive HGPS and MADA may represent a single disorder with varying degrees of severity. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Moulson et al. (2007) reported 2 unrelated patients with extremely severe forms of HGPS associated with unusual mutations in the LMNA gene. (150330.0036 and 150330.0040, respectively). Both mutations resulted in increased use of the cryptic exon 11 donor splice site observed with the common 1824C-T mutation (150330.0022). As a consequence, the ratios of mutant progerin mRNA and protein to wildtype were higher than in typical HGPS patients. The findings indicated that the level of progerin expression correlates to the severity of the disease. </p><p>In affected members of a family with adult-onset coronary disease and progeroid features, Hisama et al. (2011) identified a heterozygous splice site mutation affecting exon 11 in the LMNA gene (c.1968G-A; 150330.0055). An unrelated patient with a similar disorder carried a different splice site mutation that also affected exon 11 (c.1968+5G-A; 150330.0056). Patient cells in both cases showed the presence of progerin at lower levels than observed in typical HGPS cells. The report illustrated the evolving genotype/phenotype relationship between the amount of progerin produced and the age of onset of the spectrum of clinical features associated with LMNA-associated progeroid syndromes. In 2 unrelated patients with late-onset HGPS and cardiac disease, Barthelemy et al. (2015) identified different heterozygous exon 11 splice site mutations in the LMNA gene (150330.0055 and 150330.0056). </p><p>In affected members of a family with a protracted form of HGPS manifest as premature cutaneous and cardiac aging, Kane et al. (2013) identified a heterozygous missense mutation in the LMNA gene (D300G; 150330.0057). Skin fibroblasts derived from the proband showed abnormal morphology, including blebs, lobulation, and ringed or donut-shaped nuclei. Although the processing of lamin A and C were normal in patient cells, treatment with farnesyltransferase inhibitors resulted in improved nuclear morphology. Overexpression of the mutation in control fibroblasts led to abnormal nuclear morphology in a dominant-negative manner. </p><p>Barthelemy et al. (2015) analyzed LMNA exon 11 transcripts in cells derived from patients with atypical progeroid syndromes associated with heterozygous mutations affecting the splicing of exon 11 of the LMNA gene (150330.0055 and 150330.0056). All cells carried a normal full-length prelamin A transcript, a band corresponding to prelamin A(del50) (progerin), and an additional transcript correlating to prelamin A(del90) resulting from the skipping of all of exon 11. Barthelemy et al. (2015) termed the prelamin A(del90) transcript 'dermopathin' because it was first observed in a patient with restrictive dermopathy (275210) by Navarro et al. (2004) (see 150330.0036). Dermopathin excludes the 270 nucleotides of exon 11 and is predicted to cause an internal deletion preserving the prelamin A open reading frame (Gly567_Gln656del). The findings indicated that progerin accumulation is the major pathogenetic mechanism responsible for HGPS-like disorders due to LMNA mutations. </p><p>Bar et al. (2017) reported an 11.5-year-old girl (patient DB386) who was diagnosed with HGPS at age 10 months, at which time she exhibited typical early stage features; however, she did not develop the total alopecia pathognomonic of classic HGPS, showed less-pronounced mandibular recession, and had milder than expected joint contractures. As she aged, she also displayed better growth than expected, and at age 5.9 years, she had normal blood pressure, no insulinemia or insulin resistance, and no electrocardiographic abnormalities. Sequencing of LMNA exon 11 DNA from blood-derived WBCs and cultured skin fibroblasts revealed 2 different mutations, with blood-derived DNA showing a c.1968+2T-A variant, and all 3 fibroblast DNA isolates showing a c.1968+2T-C variant. Testing for mosaicism demonstrated approximately 50% normal LMNA sequence, with 4.7% c.1968+2T-C and 41.3% c.1968+2T-A. Bar et al. (2017) also assessed 2 additional HGPS patients, each heterozygous for 1 of the mutations: a girl (patient DB423) with the c.1968+2T-A mutation, who had a severe HGPS phenotype and died at age 3.5 years; and a boy (patient DB392) with the c.1968+2T-C mutation, who was alive at age 11.5 years with no mandibular recession, moderate alopecia, and moderate lipodystrophy. Based on these genotype/phenotype comparisons, Bar et al. (2017) proposed a novel partial phenotypic rescue mechanism, in which patient DB386 had an initial germline mutation c.1968+2T-A, followed by a rescue event during early development, in which the somatic A-C transversion at the same nucleotide provided a selective advantage. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>By light and electron microscopy of fibroblasts from HGPS patients carrying the 1824C-T mutation, Goldman et al. (2004) found significant changes in nuclear shape, including lobulation of the nuclear envelope, thickening of the nuclear lamina, loss of peripheral heterochromatin, and clustering of nuclear pores. These structural defects worsened as the HGPS cells aged in culture, and their severity correlated with an apparent accumulation of mutant protein, which Goldman et al. (2004) designated LA delta-50. Goldman et al. (2004) concluded that expression of LA delta-50 has an age-dependent, cumulative, and ultimately devastating effect on nuclear architecture and function that is responsible for premature aging in HGPS patients. </p><p>Glynn and Glover (2005) studied the effects of farnesylation inhibition on nuclear phenotypes in cells expressing normal and 1824C-T mutant lamin A. Expression of a GFP-progerin fusion protein in normal fibroblasts caused a high incidence of nuclear abnormalities (as seen in HGPS fibroblasts), and resulted in abnormal nuclear localization of GFP-progerin in comparison with the localization pattern of GFP-lamin A. Expression of a GFP-lamin A fusion containing a mutation preventing the final cleavage step, which caused the protein to remain farnesylated, displayed identical localization patterns and nuclear abnormalities as in HGPS cells and in cells expressing GFP-progerin. Exposure to a farnesyltransferase inhibitor (FTI), PD169541, caused a significant improvement in the nuclear morphology of cells expressing GFP-progerin and in HGPS cells. Glynn and Glover (2005) proposed that abnormal farnesylation of progerin may play a role in the cellular phenotype in HGPS cells, and suggested that FTIs may represent a therapeutic option for patients with HGPS. </p><p>Using various mechanical measurements, including photobleaching assays, biophysical analysis under hypo- and hyperosmotic conditions, and micropipette aspiration, Dahl et al. (2006) demonstrated that the lamina in HGPS cells has a reduced ability to rearrange after mechanical stress compared to wildtype cells. In response to dynamic changes in the cell, mutant LMNA associated more tightly with the nuclear lamina than wildtype LMNA. Polarization microscopy studies showed that the lamins in HGPS nuclei were birefringent, forming orientationally ordered microdomains with reduced deformability. Dahl et al. (2006) suggested that the altered mechanical properties of HGPS cells may lead to misexpression of mechanosensitive genes. </p><p>Hennekam (2006) noted that the HGPS-like disorder, mandibuloacrodysplasia with type B lipodystrophy (MADB; 608612), and restrictive dermopathy (275210) are both caused by mutation in the ZMPSTE24 gene (606480), resulting in abnormal posttranslational processing of lamin A. The author suggested that patients with atypical progeria may have ZMPSTE24 mutation. </p><p>Wang et al. (2006) found that cultured HGPS fibroblasts showed early accelerated growth followed by rapid decline in proliferation in later passages compared to normal cells. HGPS fibroblasts had shrunken cell bodies with coarse cell membranes starting from early passages and showed loss of cell-to-cell growth inhibition with cell clustering. HPGS nuclei also showed multiple morphologic abnormalities compared to normal fibroblasts. Using microarray, RT-PCR, and Western blot analysis, Wang et al. (2006) found significantly increased (approximately 100-fold) expression of the ANK3 gene (600465) in fibroblast cell lines from a patient with HGPS compared to a normal control cell line. </p><p>Varela et al. (2008) found that combined treatment of HGPS cells with both statins and aminobisphosphonates resulted in improved nuclear morphology and decreased accumulation of prelamin A. The mechanism of treatment involved the inhibition of farnesyl pyrophosphate synthesis and prevention of cross-prenylation of prelamin A. </p><p>Liu et al. (2011) reported the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS iPSCs showed absence of progerin, and more importantly, lacked the nuclear envelope and epigenetic alterations normally associated with premature aging. Upon differentiation of HGPS iPSCs, progerin and its aging-associated phenotypic consequences were restored. Specifically, directed differentiation of HGPS iPSCs to vascular smooth muscle cells led to the appearance of premature senescence phenotypes associated with vascular aging. Additionally, their studies identified DNA-dependent protein kinase catalytic subunit (PRKDC; 600899) as a downstream target of progerin. The absence of nuclear PRKDC holoenzyme correlated with premature as well as physiologic aging. Because progerin also accumulates during physiologic aging, Liu et al. (2011) argued that their results provided an in vitro iPSC-based model to study the pathogenesis of human premature and physiologic vascular aging. </p><p>In normal cells, heterochromatic, gene-poor, inactive regions of chromatin tend to cluster near the nuclear periphery, while open, active, gene-dense regions cluster in the nuclear interior. McCord et al. (2013) found that HGPS skin fibroblasts lost this compartmentalization at later passages. Loss of compartmentalization was preceded by loss of H3K27 trimethylation in gene-poor regions, gain of H3K27 trimethylation in gene-rich regions, and detachment of chromatin from the lamina visible by electron microscopy. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In progeria, the accumulation of farnesyl-prelamin A disrupts the structural scaffolding for the cell nucleus, leading to misshapen nuclei. Farnesyltransferase inhibitors (FTIs) can reverse this cellular abnormality (e.g., Mallampalli et al., 2005). Fong et al. (2006) tested the efficacy of an FTI (ABT-100) in Zmpste24-deficient mice, a mouse model of progeria. The FTI-treated mice exhibited improved body weight, grip strength, bone integrity, and percent survival at 20 weeks of age. Fong et al. (2006) concluded that FTIs may have beneficial effects in humans with progeria. </p><p>Yang et al. (2006) generated mice with a targeted HGPS mutation (Lmna HG/+) and observed phenotypes similar to those in human HGPS patients, including retarded growth, reduced amounts of adipose tissue, micrognathia, osteoporosis, and osteolytic lesions in bone, which caused spontaneous rib fractures in the mutant mice. Treatment with an FTI increased adipose tissue mass, improved body weight curves, reduced the number of rib fractures, and improved bone mineralization and bone cortical thickness. </p><p>Varga et al. (2006) created a mouse model for progeria harboring the common human G608G LMNA mutation (150330.0022). Mutant mice showed striking arterial changes, including progressive loss of vascular smooth muscle cells in the medial layer, elastic fiber breakage, and proteoglycan and collagen deposition in a pattern very similar to that seen in children with HGPS. Arterial calcification, adventitial thickening, and severe loss of vascular smooth muscle cells was observed in older mutant mice. Older mutant mice also showed impaired blood pressure regulation. </p><p>In conditional transgenic mice with a human LMNA mutation, Sagelius et al. (2008) observed external features of the syndrome, including hair thinning and skin crusting, at postnatal week 4. After phenotype development, transgenic expression was turned off, and there was a rapid improvement of the phenotype within 4 weeks of transgenic suppression. After 13 weeks, pathologic examination showed that skin from the mutant mice was almost indistinguishable from wildtype skin, and there was also improvement in teeth. Sagelius et al. (2008) concluded that, in these tissues, expression of the progeria mutation did not cause irreversible damage and that reversal of disease phenotype is possible. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Ayres and Mihan (1974) suggested that a fault in vitamin E metabolism may be at the root of progeria and recommended vitamin E therapy for its antioxidant effect. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Brown and Darlington (1980); Goldstein and Moerman (1975); Harley et
al. (1981); Rautenstrauch et al. (1977); Viegas et al. (1974)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
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Ayres, S. C., Mihan, R.
<strong>Progeria: a possible therapeutic approach. (Letter)</strong>
JAMA 227: 1381-1382, 1974.
[PubMed: 4406015]
[Full Text: https://doi.org/10.1001/jama.1974.03230250013009]
</p>
</li>
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<p class="mim-text-font">
Bar, D. Z., Arlt, M. F., Brazier, J. F., Norris, W. E., Campbell, S. E., Chines, P., Larrieu, D., Jackson, S. P., Collins, F. S., Glover, T. W., Gordon, L. B.
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<p class="mim-text-font">
Barthelemy, F., Navarro, C., Fayek, R., Da Silva, N., Roll, P., Sigaudy, S., Oshima, J., Bonne, G., Papadopoulou-Legbelou, K., Evangeliou, A. E., Spilioti, M., Lemerrer, M., Wevers, R. A., Morava, E., Robaglia-Schlupp, A., Levy, N., Bartoli, M., De Sandre-Giovannoli, A.
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<p class="mim-text-font">
Brown, W. T., Abdenur, J., Goonewardena, P., Alemzadeh, R., Smith, M., Friedman, S., Cervantes, C., Bandyopadhyay, S., Zaslav, A., Kunaporn, S., Serotkin, A., Lifshitz, F.
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<p class="mim-text-font">
Brown, W. T., Darlington, G. J., Arnold, A., Fotino, M.
<strong>Detection of HLA antigens on progeria syndrome fibroblasts.</strong>
Clin. Genet. 17: 213-219, 1980.
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<p class="mim-text-font">
Brown, W. T., Darlington, G. J.
<strong>Thermolabile enzymes in progeria and Werner syndrome: evidence contrary to the protein error hypothesis.</strong>
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Brown, W. T.
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<p class="mim-text-font">
Brown, W. T.
<strong>Personal Communication.</strong>
Staten Island, N.Y. 1/12/2004.
</p>
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<p class="mim-text-font">
Cao, H., Hegele, R. A.
<strong>LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).</strong>
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Cao, K., Graziotto, J. J., Blair, C. D., Mazzulli, J. R., Erdos, M. R., Krainc, D., Collins, F. S.
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Chen, L., Lee, L., Kudlow, B. A., Dos Santos, H. G., Sletvold, O., Shafeghati, Y., Botha, E. G., Garg, E., Hanson, N. B., Martin, G. M., Mian, I. S., Kennedy, B. K., Oshima, J.
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Dahl, K. N., Scaffidi, P., Islam, M. F., Yodh, A. G., Wilson, K. L., Misteli, T.
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De Martinville, B., Sorin, M., Briard, M. L., Frezal, J.
<strong>Progeria de Gilford-Hutchinson a debut neonatal chez des jumeaux monozygotes.</strong>
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de Paula Rodrigues, G. H., das Eiras Tamega, I., Duque, G., Spinola Dias Neto, V.
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De Sandre-Giovannoli, A., Bernard, R., Cau, P., Navarro, C., Amiel, J., Boccaccio, I., Lyonnet, S., Stewart, C. L., Munnich, A., Le Merrer, M., Levy, N.
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DeBusk, F. L.
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Delgado Luengo, W.., Rojas Martinez, A., Ortiz Lopez, R., Martinez Basalo, C., Rojas-Atencio, A., Quintero, M., Borjas, L., Morales-Machin, A., Gonzalez Ferrer, S., Pineda Bernal, L., Canizalez-Tarazona, J., Pena, J., Delgado Luengo, J., Chacin Hernandez, J., Chang, J. C.
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Dyck, J. D., David, T. E., Burke, B., Webb, G. D., Henderson, M. A., Fowler, R. S.
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Erecinski, K., Bittel-Dobrzynska, N., Mostowiec, S.
<strong>Zespol progerii u dwoch braci.</strong>
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<p class="mim-text-font">
Eriksson, M., Brown, W. T., Gordon, L. B., Glynn, M. W., Singer, J., Scott, L., Erdos, M. R., Robbins, C. M., Moses, T. Y., Berglund, P., Dutra, A., Pak, E., Durkin, S., Csoka, A. B., Boehnke, M., Glover, T. W., Collins, F. S.
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<p class="mim-text-font">
Fatunde, O. J., Benka-Coker, L. B. O., Scott-Emuakpor, A. B.
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<p class="mim-text-font">
Fong, L. G., Frost, D., Meta, M., Qiao, X., Yang, S. H., Coffinier, C., Young, S. G.
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Gabr, M., Hashem, N., Hashem, M., Fahmi, A., Safouh, M.
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<p class="mim-text-font">
Gilford, H.
<strong>Ateleiosis and progeria: continuous youth and premature old age.</strong>
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</p>
</li>
<li>
<p class="mim-text-font">
Glynn, M. W., Glover, T. W.
<strong>Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition.</strong>
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<p class="mim-text-font">
Goldman, R. D., Shumaker, D. K., Erdos, M. R., Eriksson, M., Goldman, A. E., Gordon, L. B., Gruenbaum, Y., Khuon, S., Mendez, M., Varga, R., Collins, F. S.
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</p>
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<li>
<p class="mim-text-font">
Goldstein, S., Moerman, E. J.
<strong>Heat-labile enzymes in skin fibroblasts from subjects with progeria.</strong>
New Eng. J. Med. 292: 1305-1309, 1975.
[PubMed: 1128606]
[Full Text: https://doi.org/10.1056/NEJM197506192922501]
</p>
</li>
<li>
<p class="mim-text-font">
Goldstein, S., Moerman, E. J.
<strong>Heat-labile enzymes in circulating erythrocytes of a progeria family.</strong>
Am. J. Hum. Genet. 30: 167-173, 1978.
[PubMed: 655163]
</p>
</li>
<li>
<p class="mim-text-font">
Harley, C. B., Goldstein, S., Posner, B. I., Guyda, H.
<strong>Decreased sensitivity of old and progeric human fibroblasts to a preparation of factors with insulinlike activity.</strong>
J. Clin. Invest. 68: 988-994, 1981.
[PubMed: 7026617]
[Full Text: https://doi.org/10.1172/jci110353]
</p>
</li>
<li>
<p class="mim-text-font">
Hegele, R. A.
<strong>Drawing the line in progeria syndromes.</strong>
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[PubMed: 3728539]
[Full Text: https://doi.org/10.1016/0002-9343(86)90196-8]
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Parkash, H., Sidhu, S. S., Raghavan, R., Deshmukh, R. N.
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Paterson, D.
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Proc. Roy. Soc. Med. 16: 42 only, 1922.
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[Full Text: https://doi.org/10.1136/jmg.2008.060772]
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Varela, I., Pereira, S., Ugalde, A. P., Navarro, C. L., Suarez, M. F., Cau, P., Cadinanos, J., Osorio, F. G., Foray, N., Cobo, J., de Carlos, F., Levy, N., Freije, J. M. P., Lopez-Otin, C.
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Verstraeten, V. L. R. M., Broers, J. L. V., van Steensel, M. A. M., Zinn-Justin, S., Ramaekers, F. C. S., Steijlen, P. M., Kamps, M., Kuijpers, H. J. H., Merckx, D., Smeets, H. J. M., Hennekam, R. C. M., Marcelis, C. L. M., van den Wijngaard, A.
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<strong>Progeria in twins.</strong>
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[PubMed: 4443987]
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Wang, J., Robinson, J. F., O'Neil, C. H., Edwards, J. Y., Williams, C. M., Huff, M. W., Pickering, J. G., Hegele, R. A.
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Yang, S. H., Meta, M., Qiao, X., Frost, D., Bauch, J., Coffinier, C., Majumdar, S., Bergo, M. O., Young, S. G., Fong, L. G.
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[PubMed: 16862216]
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